Research activity information

• Dec. 2016 The Society of Synthetic Organic Chemistry, Incentive Award in Synthetic Organic Chemistry, Japan, 新規合成方法論の開発を基盤とする含窒素高次縮環天然物の全合成

  OKANO KENTARO

  Japan society


• 2014 Georg Thieme Verlag KG, Thieme Chemistry Journal Award 2015, Awardees are loosely defined as promising young professors at the beginning of their career.

  OKANO KENTARO

  Publisher


• 2013 天然物化学談話会, 平成25年度 天然物化学談話会 奨励賞, 特異な含窒素縮合環を有する天然有機化合物の合成研究

  OKANO KENTARO

  Japan society


• 2012 日本薬学会, 平成24年度 日本薬学会東北支部 奨励賞, 芳香族炭素－窒素結合形成法の開発を鍵とする含窒素芳香族天然物の合成研究

  OKANO KENTARO

  Japan society


• 2011 井上科学振興財団, 第27回 井上研究奨励賞, Enantioselective Total Synthesis of (+)-Yatakemycin Based on CuI-Mediated Aryl Amination

  OKANO KENTARO

  Japan society


• 2011 Inoue Research Award for Young Scientists


• 2009 有機合成化学協会, 2009年度 有機合成化学協会 旭化成ファーマ研究企画賞, 配位子による触媒 機能の動的変化を基盤とするワンポット多成分連続反応の開発

  OKANO KENTARO

  Japan society

• Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply-fused heteroaromatic compounds

  Yuki Nakanishi, Shoichi Sugita, Kentaro Okano, Atsunori Mori

  The C–H arylation of 2-quinolinecarboxyamide bearing C–Br bond at the N-aryl moiety is carried out with a palladium catalyst. The reaction proceeds at the C–H bond on the pyridine ring adjacent to the amide group in the presence of 10 mol% Pd(OAc)₂ at 110 °C to afford the cyclized product in 42% yield. The yield is improved to 94% when the reaction is performed with PPh₃ as a ligand of palladium. The reaction is examined with amides derived from unsubstituted picoline, 6-methyl-picoline, and 2,6-pyridinedicarboxylic acid in a similar manner to afford the cyclized product in 70%, 77%, 87%, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benz- amides to afford multiply-fused heterocyclic compounds in 81% and 89% yields, respectively.

  Beilstein Institut, Nov. 2024


• A concise synthesis of multiply fused phenanthroline diamide (fused-PTDA) by palladium-catalyzed intramolecular C–H arylation. Highly efficient and selective extraction performance of fused-PTDA toward early lanthanides

  Towa Asano, Yuki Nakanishi, Shoichi Sugita, Kentaro Okano, Hirokazu Narita, Tohru Kobayashi, Tsuyoshi Yaita, Atsunori Mori

  The reaction of phenanthroline diamide bearing a bromoaryl moiety on the amide substituent in the presence of palladium catalyst proceeded efficiently to afford multiply-fused phenanthroline derivatives through intramolecular C–H arylation. The obtained diamide derivatives was found to extract lanthanide remarkably highly efficiently with distribution ratio (D: up to ca. 500) and it was also found show the metal-selective extraction (separation factor SF = up to 4.4).

  American Chemical Society (ACS), Sep. 2024


• Gram-Scale Total Synthesis of Carbazomycins A-D through Late-Stage Regioselective Demethylation of Aryl Methyl Ethers

  Yuxuan Feng, Atsunori Mori, Kentaro Okano

  Gram-scale total synthesis of carbazomycins A-D is described. The total synthesis of carbazomycin A was achieved in 44% overall yield over six steps from symmetrical 5-chloro-1,2,3-trimethoxybenzene. The key aryne-mediated carbazole formation and methylation steps provided the multiply substituted carbazole. The regioselective demethylation of the trimethoxycarbazole was performed using boron trichloride. Thereafter, the phenolic hydroxy group was converted into the methyl group to provide carbazomycin A. Subsequent installation of the methoxy group realized the total synthesis of carbazomycin D. Regioselective demethylation was performed using 1-dodecanethiol, effecting the conversions of carbazomycins A and D into carbazomycins B and C, respectively.

  Sep. 2024, Journal of Organic Chemistry, 89(18) (18), 13472 - 13484

  Scientific journal


• Synthesis of head-to-tail-type poly(1,3-phenylene) with high degrees of polymerization catalyzed by Nickel(II)-(N-heterocyclic Carbene) complex

  Seiha Yamaoka, Koki Susami, Shuichi Ikeda, Masaki Horie, Hideto Minami, Nozomu Suzuki, Kentaro Okano, Atsunori Mori

  Aug. 2024, ChemRxiv, English


• Catalytic Approaches to the Halogen Dance Reaction for Molecular Editing

  Kengo Inoue, Kentaro Okano

  Transposition reactions, i. e., switching the position of functional groups, are a powerful tool for molecular editing. The transposition of a halogen atom attached to an aromatic ring, referred to as the halogen dance reaction, has great potential in the fields of pharmaceuticals, agrochemicals, natural products, and functional materials. However, the substrate scope of this reaction is limited owing to the intrinsic difficulty in facilitating multiple catalytic cycles involving several aryllithium species. In this concept paper, recent advances in halogen dance catalysis that have expanded the substrate scope of this reaction are highlighted.

  Jul. 2024, ChemCatChem, 16(14) (14)

  Scientific journal


• Total Synthesis of Carbazomycins E and F

  Yunosuke Shima, Yuxuan Feng, Atsunori Mori, Kentaro Okano

  Total synthesis of carbazomycins E and F was achieved by double functionalization of an aryne intermediate generated from a 2-aminobiphenyl derivative. The tethered amino group underwent nucleophilic addition to the aryne intermediate to construct the carbazole skeleton. The resulting carbanion was formylated to give the multiply substituted carbazole. This formyl group caused several problems. For example, it was difficult to perform regioselective demethylation of the methoxy group proximal to the formyl group without protecting the carbazole nitrogen. In addition, the formyl group was unexpectedly reduced to give a methoxymethyl group under heating conditions with copper iodide and sodium methoxide. Oxidation of this compound in the presence of water was effective for obtaining the formylated carbazole, leading to the first total synthesis of carbazomycin F.

  Jun. 2024, Journal of Organic Chemistry, 89(11) (11), 8185 - 8191

  Scientific journal


• High‐Intensity Circular Dichroism of Head‐to‐tail Regioregular Poly(1,4‐phenylene)s in the Aggregated State

  Rikuya Tanaka, Seiha Yamaoka, Shuichi Ikeda, Kentaro Okano, Masaki Horie, Hideto Minami, Nozomu Suzuki, Atsunori Mori

  Circular dichroism (CD) studies on poly(1,4‐phenylene)s bearing a chiral side chain in the aggregated conditions were carried out. Little CD was observed in a solution form, while addition of a poor solvent into the polyphenylene solution induced aggregation and a strong CD was observed, accordingly. Applying the controlled degree of polymerization (DP) of poly(1,4‐phenylene) in the use of bidentate diphosphine Chiraphos as a ligand for the nickel catalyst, the relationship of DP with CD strength was studied to reveal to show the highest CD at the DP = 84 (gabs = ca. 2 x 10–2). It was also found that the related aggregation was observed in good solvent 1,2‐dichloroethane upon standing the solution at 4 °C for 3–23 days to observe gabs = ca. 10–1. Studies on the substituent effect of poly(1,4‐phenylene) suggested that CD behaviors were dependent on the type of non‐chiral substituent on the aromatic ring as well as the side‐chain chirality.

  Wiley, Apr. 2024, Chemistry – A European Journal, 30(35) (35)

  Scientific journal


• A Ni0(cod)(dq) (COD: 1,5-cycloctadiene; DQ: duroquinone) complex as a catalyst precursor for oligothiophene and polythiophene synthesis.

  Naoki Noda, Seiha Yamaoka, Ukyo Ogi, Masaki Horie, Kentaro Okano, Atsunori Mori

  Nickel-catalyzed syntheses of oligothiophene and polythiophene were carried out with Ni(cod)(dq) (COD: 1,5-cycloctadiene; DQ: duroquinone) as a catalyst precursor. Studies on the ligand exchange of Ni(cod)(dq) revealed that a high temperature was necessary to replace COD and DQ with PPh3 and N-heterocyclic carbene IPr. A coupling reaction of a metalated 3-hexylthiophene with 2-chloro-3-hexylthiophene employing Ni(cod)(dq) with IPr proceeded with a remarkably reduced amount of homocoupling byproduct. Polymerization of 2-chloro-3-hexylthiophene with Ni(cod)(dq)/DPPP also resulted in the reduction of the regioregularity defect.

  Mar. 2024, Organic & biomolecular chemistry, 22(13) (13), 2574 - 2579, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Synthesis and properties of polythiophenes bearing alkylsulfonic acid esters at the side chain

  Aika Kuwayama, Sonoka Yamamoto, Yuma Sakagami, Mizuho Yamagishi, Kentaro Okano, Masaki Horie, Masahiro Funahashi, Atsunori Mori

  Introduction of alkylsulfonic acid moieties into the side chain of polythiophene was carried out. Synthesis of 2,5-dihalothiophenes bearing alkylsulfonate groups at the 3-position was performed. The reaction of 2-chloro-5-iodothiophenes with Grignard reagents to form the organometallic monomers of the corresponding thiophenes followed by nickel(ii)-catalyzed cross-coupling polymerization led to head-to-tail-type regioregular polythiophenes. The ester groups at the side chains were converted into alkali metal sulfonates by treatment with NaI or metal hydroxides (Li, Na, K). The obtained metal salts were successfully transformed into sulfonic acid groups by treatment with an ion exchange resin. The electric conductivity of the regioregular polythiophene bearing sulfonic acid groups was remarkably improved ca. 102 times compared to the corresponding metal salts (106 times higher than the sulfonate ester).

  Mar. 2024, Polymer Chemistry, 15(16) (16), 1635 - 1641

  Scientific journal


• Ultrafast Halogen Dance Reactions of Bromoarenes Enabled by Catalytic Potassium Hexamethyldisilazide.

  Kengo Inoue, Atsunori Mori, Kentaro Okano

  Lochmann-Schlosser base, a stoichiometric combination of nBuLi and KOtBu, is commonly used as a superbase for deprotonating a wide range of organic compounds. In the present study, we report that catalytic potassium hexamethyldisilazide (KHMDS) exhibits higher catalytic activity than KOtBu for successive bromine-metal exchanges. Accordingly, 1-10 mol% of KHMDS dramatically enhances halogen dance reactions to introduce various electrophiles to bromopyridine, bromoimidazole, bromothiophene, bromofuran, and bromobenzene derivatives with the bromo group translocated from the original position. A dual catalytic cycle is proposed to explain the ultrafast bromine transfer.

  Feb. 2024, Chemistry (Weinheim an der Bergstrasse, Germany), 30(23) (23), e202400104, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Double Winding Vine-Shaped Biphenyl with Molecular Asymmetry. Synthesis, Structure, and Properties

  Atsunori Mori, Aruto Maruka, Kohei Tabuchi, Kentaro Okano, Masaki Horie

  A biphenyl derivative in which two benzene rings are strapped with two chains is prepared. The synthesized product shows molecular asymmetry, which was confirmed by HPLC analysis with chiral column and named as winding vine-shaped biphenyl. The synthesis of such vine shaped molecule was performed by ring-closing metathesis or alternatively by annulation with nosylated ethylenediamine. The structure of the obtained product was confirmed by X-ray crystallographic analysis. The absolute configuration of the molecular asymmetry was assigned after leading to the corresponding camphor sulfonamide through denosylation and re-amidation process.

  2024, European Journal of Organic Chemistry, 27(20) (20)

  Scientific journal


• Studies on circular dichroism behaviors of aggregated poly(1,4-phenylene)s with head-to-tail regioregularity

  Rikuya Tanaka, Seiha Yamaoka, Shuichi Ikeda, Kentaro Okano, Masaki Horie, Hideto Minami, Nozomu Suzuki, Atsunori Mori

  Dec. 2023, ChemRxiv, English


• A high macro molecular ghost in SEC analysis of conjugate polymer

  Seiha Yamaoka, Kentaro Okano, Atsunori Mori

  Nov. 2023, ChemRxiv, English


• Ultra-Fast Halogen Dance Enabled by Catalytic KHMDS

  Kengo Inoue, Atsunori Mori, Kentaro Okano

  Catalytic potassium hexamethyldisilazide (KHMDS) accelerates a bromine–metal exchange rather than potassium tert-butoxide (KOtBu), which is stoichiometrically used for the Lochmann–Schlosser base, a combination of nBuLi and KOtBu. Loading of 1.0–10 mol% of KHMDS drastically facilitated successive bromine–metal exchanges consisting of a halogen dance reaction within 1 min to introduce various electrophiles on bromopyridine, imidazole, thiophene, furan, and benzene derivatives with the bromo group translocated from the original position. A dual catalytic cycle is proposed to explain the ultra-fast bromine transfer showing the significant potential to realize new catalytic reactions of aryllithium species using KHMDS.

  American Chemical Society (ACS), Nov. 2023


• Formal Halogen Transfer of Bromoarenes via Stepwise Reactions

  Kengo Inoue, Atsunori Mori, Kentaro Okano

  American Chemical Society (ACS), Aug. 2023, Organic Letters, 25(36) (36), 6693 - 6698

  [Refereed]

  Scientific journal


• Studies on the stereochemical behaviors of a winding vine-shaped molecular wire of a bithiophene dimer with molecular asymmetry

  Kohei Hosokawa, Kohei Tabuchi, Yuki Nakanishi, Kentaro Okano, Masaki Horie, Atsunori Mori

  Multiple ring-closing metathesis of oligomeric bithiophene smoothly formed a winding vine-shaped oligomer with molecular asymmetry. Stereochemical studies suggested that the dimeric 1 : 1 meso and racemic stereochemical mixture showed the conversion to a meso-enriched product upon standing in the solid state, while the obtained meso compound reverted to the meso and racemic mixture upon heating the solution in chloroform at 50 °C for 30 min. On the other hand, heating of the meso isomer in the solid state at 80 °C for 3 days did not lead to isomerization.

  Jul. 2023, Molecular Systems Design and Engineering, 8(10) (10), 1252 - 1256

  [Refereed]

  Scientific journal


• Regiodivergent Synthesis of Brominated Pyridylthiophenes by Overriding the Inherent Substrate Bias

  Masahiro Hosoya, Atsunori Mori, Kentaro Okano

  A regiocontrolled functionalization of a pyridylthiophene scaffold was accomplished. Regioselectivity for deprotonation of the pyridylthiophene was switched by changing the reaction conditions, including the metal amide base and the solvent. Subsequently, in situ transmetalation and halogen dance on the corresponding organometallic species were controlled by additives and the reaction temperature, as well as by the above reaction conditions. This method successfully enabled the synthesis of four iodinated constitutional isomers from a single starting material, 2-(5-bromo-2-thienyl)pyridine.

  GEORG THIEME VERLAG KG, Jul. 2023, SYNLETT, English

  [Refereed][Invited]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Deprotonative Generation and Trapping of Haloaryllithium in a Batch Reactor.

  Yuxuan Feng, Taro Yukioka, Mei Matsuyama, Atsunori Mori, Kentaro Okano

  A method for the regioselective functionalization of haloarenes through deprotonative lithiation is disclosed. The generated haloaryllithiums were trapped in a batch reactor with a zinc chloride diamine complex to provide organozinc species without aryne formation, which reacted with electrophiles to afford the corresponding products in 38-98% yields. This method was applied to the five-step total synthesis of carbazomycin A on a gram scale in 33% overall yield.

  May 2023, Organic letters, 25(17) (17), 3013 - 3017, English, International magazine

  [Refereed]

  Scientific journal


• Formal Synthesis of Dictyodendrin B.

  Yuya Okui, Atsunori Mori, Kentaro Okano

  A formal synthesis of dictyodendrin B is described. Regiocontrolled functionalization of the α,β-dibromopyrrole derivative provided the fully substituted pyrrole bearing an indole moiety. Subsequent reductive cyclization using a combination of sodium dispersion and triethylsilyl chloride enabled the formation of the benzene ring in the characteristic tetracyclic pyrrolo[2,3-c]carbazole skeleton, while the ethyl ester remained untouched. Further chemical transformation of the ester moiety and functional group manipulation completed the formal synthesis of dictyodendrin B.

  Apr. 2023, Organic letters, 25(15) (15), 2669 - 2673, English, International magazine

  [Refereed]

  Scientific journal


• Lithium Aryltrifluoroborate as a Catalyst for Halogen Transfer

  Kengo Inoue, Keiichi Hirano, Shota Fujioka, Masanobu Uchiyama, Atsunori Mori, Kentaro Okano

  Mar. 2023, ACS Catalysis

  [Refereed]

  Scientific journal


• Nickel(II) Thiocyanate Complex as a Catalyst for Cross-Coupling Reactions

  Seiha Yamaoka, Hiroyuki Fukuoka, Naoki Noda, Kentaro Okano, Masaki Horie, Atsunori Mori

  A nickel thiocyanate complex was prepared by the reaction of Ni(NCS)2 with (2S,3S)-2,3-bis(diphenylphosphino)butane (Chiraphos) by following a method reported in the literature. The resulting nickel complex was found to be active in the polymerization reactions of 1,4-dihalobenzenes and 2-halo-3-hexylthiophenes, leading to poly-1,4-phenylenes and poly(3-hexylthiophene-2,5-diyl), respectively. The polymerization in the presence of similar catalysts containing other ligands, such as 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenyl-phosphino)propane, or N-heterocyclic carbenes, also proceeded in a similar manner. Ni(NCS)2 complexes also successfully catalyzed Suzuki–Miyaura couplings and Buchwald–Hartwig aminations to afford the corresponding biaryls and arylamines, respectively.

  Feb. 2023, Synlett, 34(20) (20), 2401 - 2404

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Use of Chiraphos as a Highly Efficient Ligand in the Nickel(II)-catalyzed Cross-coupling Polymerization for the synthesis of Poly(1,4-arylene)s

  Yushin Shibuya, Koki Susami, Hiroyuki Fukuoka, Seiha Yamaoka, Kentaro Okano, Atsunori Mori

  The Chemical Society of Japan, Feb. 2023, Chemistry Letters, 52(2) (2), 116 - 119, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Regiocontrolled halogen dance of 2,5-dibromopyrroles using equilibrium between dibromopyrrolyllithiums

  Tatsuki Okumi, Atsunori Mori, Kentaro Okano

  A regiocontrolled halogen dance reaction of 2,5-dibromopyrroles is described. An N,N-dimethylsulfamoyl group on the pyrrole nitrogen was especially effective for facilitating interconversion of the resulting 2,3- and 2,4-dibromopyrrolyllithiums, rendering the smooth halogen dance reaction. This method was applicable to the formal synthesis of atorvastatin.

  ROYAL SOC CHEMISTRY, Jan. 2023, CHEMICAL COMMUNICATIONS, 59(8) (8), 1046 - 1049, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Orthogonal electric and ionic conductivities in the thin film of thiophene–thiophene block copolymer

  Sonoka Yamamoto, Ryutaro Yamashita, Chihiro Kubota, Kentaro Okano, M. Kitamura, Masahiro Funahashi, SyuCheng Ye, Yung-Tin Pan, Masaki Horie, Takuji Shintani, Hironori Murata, Hideto Matsuyama, Atsunori Mori

  Thiophene–thiophene block copolymer composed of hydrophilic and hydrophobic side chain functionalities was designed and synthesized. Deprotonative metalation nickel-catalyzed polymerization protocol successfully afforded the block copolymer, which side chains are derived...

  Royal Society of Chemistry (RSC), 2023, Journal of Materials Chemistry C

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Generation of Sodium‐Thiophene Species with Metal Amide‐Free Approach Toward Polythiophene Synthesis by Cross‐Coupling Polymerization

  Tomoki Inoue, Aika Kuwayama, Kentaro Okano, Masaki Horie, Atsunori Mori

  Wiley, Aug. 2022, Asian Journal of Organic Chemistry, 11(8) (8)

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Studies on the Properties of Poly(3-alkylthiophene) Copolymerized by a Small Amount of Thiophene Derivative Bearing a Cyclic Siloxane Moiety at the Side Chain

  Chihiro Kubota, Masaki Kashimoto, Ryutaro Yamashita, Kentaro Okano, Masaki Horie, Masahiro Funahashi, Takuya Matsumoto, Takashi Nishino, Atsunori Mori

  The Chemical Society of Japan, Jun. 2022, Bulletin of the Chemical Society of Japan, 95(6) (6), 882 - 888

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance

  Kentaro Okano, Yuya Okui, Yuto Yasuda, Atsunori Mori

  Abstract A total synthesis of lamellarins U and A3 is described. The synthesis features the interruption of a halogen dance reaction of a metalated α,β-dibromopyrrole. The pyrrolylmagnesium reagent, generated by deprotonative metalation by using (TMP)MgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidide) as the base, was transmetalated to the corresponding organozinc species without causing the halogen dance reaction, which underwent a Negishi coupling to incorporate an aryl group onto the pyrrole ring. The arylated α,β-dibromopyrrole was then converted into lamellarins U and A3 through an α-selective halogen–magnesium exchange followed by carboxylation and subsequent palladium-mediated cyclization. The late-stage introduction of another aryl group was performed using a Kosugi–Migita–Stille coupling to provide lamellarins U and A3.

  Georg Thieme Verlag KG, Jun. 2022, Synthesis, 54(11) (11), 2647 - 2660

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Cross-Coupling Polymerization of Organosodium for Polythiophene Synthesis

  Tomoki Inoue, Sonoka Yamamoto, Yuma Sakagami, Masaki Horie, Kentaro Okano, Atsunori Mori

  Treatment of 2-chloro-3-hexylthiophene with sodium 2,2,6,6-tetramethylpiperidin-1-yl (TMPNa) in hexane resulted in deprotonation at the 5-position to afford the thiophene-sodium species, whose formation was confirmed by quenching with iodine, leading to 2-chloro-3-hexyl-5-iodothiophene in 85% yield. Addition of a nickel catalyst bearing an N-heterocyclic carbene (NHC) to the thus-formed thiophene-sodium species in cyclopentyl methyl ether induced a cross-coupling polymerization at -20 °C. After the reaction mixture was stirred for 24 h, poly(3-hexylthiophen-2,5-diyl) was obtained in 56% yield. The average molecular weight Mn was revealed to be 9700, which was close to the theoretical molecular weight (M = 8500) on the basis of the monomer feed/catalyst loading ratio (2.0 mol %), and the molecular weight distribution was found to be 2.1.

  Nov. 2021, Organometallics, 40(21) (21), 3506 - 3510

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Total Synthesis of Lamellarins G, J, L, and Z Using One-Pot Halogen Dance/Negishi Coupling

  Kazuki Morii, Yuto Yasuda, Daiki Morikawa, Atsunori Mori, Kentaro Okano

  A bottom-up synthesis of lamellarins G, J, L, and Z was achieved via one-pot halogen dance/Negishi coupling of a lithiated dibromopyrrole derivative. The easily accessible dibromo-pyrrole bearing an ester moiety underwent halogen dance smoothly at -78 degrees C within 10 min. The resultant alpha-pyrrolyllithium was transmetalated to the corresponding organozinc species, which was then coupled with an aryl iodide in the presence of catalytic palladium to provide the fully substituted pyrrole. Subsequent halogen-lithium exchange was performed to incorporate a boronate group exclusively at the beta position proximal to the ester moiety. This synthetic intermediate allowed stepwise diarylation for the total synthesis of lamellarins G, J, L, and Z.

  Corresponding, AMER CHEMICAL SOC, Oct. 2021, JOURNAL OF ORGANIC CHEMISTRY, 86(19) (19), 13388 - 13401, English

  [Refereed]

  Scientific journal


• One-Shot Deprotonative Metalation/Transmetalation/Polymerization of Halothiophenes Catalyzed by Nickel Complex for Polythiophene Synthesis

  Sonoka Yamamoto, Yushin Shibuya, Toyoko Suzuki, Kentaro Okano, Masaki Horie, Atsunori Mori

  Effect of divalent metals was studied in the cross-coupling polymerization of thiophenes leading to head-to-tail-type poly-3-hexyl­thiophene. Deprotonation of the C-H bond at the 5-position of 2-halo-3-hexylthiophene by LDA followed by metal exchange was carried out in one pot and following addition of nickel catalyst underwent polymerization. One-shot reaction involving deprotonation/transmetalation/ cross coupling polymerization was also examined with manganese(II) chloride and nickel(II) catalyst.

  Sep. 2021, Synthesis (Germany), 53(17) (17), 3081 - 3084

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• "Snapshot" Trapping of Multiple Transient Azolyllithiums in Batch.

  Kengo Inoue, Yuxuan Feng, Atsunori Mori, Kentaro Okano

  Recent developments in flow microreactor technology have allowed the use of transient organolithium compounds that cannot be realized in a batch reactor. However, trapping the transient aryllithiums in a "halogen dance" is still challenging. Herein is reported the trapping of such short-lived azolyllithiums in a batch reactor by developing a finely tuned in situ zincation using zinc halide diamine complexes. The reaction rate is controlled by the appropriate choice of diamine ligand. The reaction is operationally simple and can be performed at 0 °C with high reproducibility on a multigram scale. This method was applicable to a wide range of brominated azoles allowing deprotonative functionalization, which was used for the concise divergent syntheses of both constitutional isomers of biologically active azoles.

  Corresponding, Jul. 2021, Chemistry (Weinheim an der Bergstrasse, Germany), 27(40) (40), 10267 - 10273, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• "Snapshot" Trapping of Multiple Transient Azolyllithiums in Batch.

  Kengo Inoue, Yuxuan Feng, Atsunori Mori, Kentaro Okano

  Invited for the cover of this issue is Kentaro Okano and co-workers at Kobe University. The image depicts that the 'dancing' transient organolithiums in the 'halogen dance' are successfully trapped in a batch reactor as if their individual snapshots were taken. Read the full text of the article at 10.1002/chem.202101256.

  Corresponding, Jul. 2021, Chemistry (Weinheim an der Bergstrasse, Germany), 27(40) (40), 10214 - 10214, English, International magazine

  [Refereed]


• Synthesis and Racemization Studies of Winding Vine-Shaped Biphenyl Derivatives

  Masayasu Hayashi, Jiaqiang Cheng, Kohei Hosokawa, Takumi Hatta, Chi Hsien Wang, Masaki Horie, Kentaro Okano, Atsunori Mori

  Winding vine-shaped biphenyl derivatives were synthesized through the annulation reaction of nosylated (2-nitrobenzenesulfonyl) ethylenediamine and the E-selective ring-closing metathesis reaction. The structures of the cyclized products were confirmed by measurements of 1H and 13C NMR spectra and single crystal X-ray analyses. The obtained cyclic product was revealed to exhibit molecular asymmetry, which was confirmed by HPLC analyses on chiral stationary phase. Compared with our previous results on the related bithiophene derivatives, the obtained vine-shaped biphenyls were shown to hardly racemize under ambient conditions and experimental studies on racemization behaviors suggested energy barriers of 134 kJmol−1 to 211 kJmol−1. These results reasonably agreed with those of the calculated values based on DFT.

  Jun. 2021, European Journal of Organic Chemistry, 2021(24) (24), 3465 - 3471

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Preparation of 2-(Triethylsilyl)cyclohex-1-en-1-yl Trifluoromethanesulfonate as a Precursor to Cyclohexyne

  Kazuki Inoue, Kengo Inoue, Atsunori Mori, Kentaro Okano

  Organic Syntheses, 2021, Organic Syntheses, 98, 509 - 530, English

  [Refereed]

  Scientific journal


• Preparation of 6-(Triethylsilyl)cyclohex-1-en-1-yl trifluoromethanesulfonate as a precursor to 1,2-cyclohexadiene

  Ryo Nakura, Kazuki Inoue, Mayu Itoh, Atsunori Mori, Kentaro Okano

  Corresponding, 2021, Organic Syntheses, 98, 407 - 429

  [Refereed]

  Scientific journal


• Thermally-induced doping of the regioregular polythiophene bearing alkylene spacered benzenesulfonate group at the side chain

  Chihiro Kubota, Daisuke Morita, Keisuke Fujita, Sonoka Yamamoto, Toyoko Suzuki, Kentaro Okano, Masahiro Funahashi, Masaki Horie, Atsunori Mori

  Regioregular polythiophene bearing a benzenesulfonate group, which involved an alkylene spacer between thiophene and benzene ring, was synthesized. The obtained polythiophene was shown to improve its conductivity by heating the polymer thin film through the transformation of the ester group into the corresponding sulfonic acid.

  2021, Heterocycles, 103(1) (1)

  [Refereed]

  Scientific journal


• Trapping of Transient Thienyllithiums Generated by Deprotonation of 2,3- or 2,5-Dibromothiophene in a Flow Microreactor

  Kentaro Okano, Yoshiki Yamane, Aiichiro Nagaki, Atsunori Mori

  Selective trapping of (4,5-dibromo-2-thienyl)lithium, known to undergo halogen dance, was achieved in a flow microreactor. This transient thienyllithium, generated by mixing 2,3-dibromothiophene and lithium diisopropylamide at –78 °C for 1.6 seconds, reacted with benzaldehyde. The reaction system is also applicable to other carbonyl compounds to afford the corresponding adducts in good yields. Moreover, the established conditions permit the conversion of 2,5-dibromothiophene into a mixture of the two constitutional isomers. The contrasting results are discussed on the basis of the reaction pathway.

  Corresponding, Georg Thieme Verlag KG, Dec. 2020, Synlett, 31(19) (19), 1913 - 1918

  [Refereed][Invited]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Synthesis of Multiply Substituted Heteroarenes Using Halogen Dance

  Kentaro Okano

  A lithium amide-promoted halogen dance of 2,5-dibromothiophene led to the formation of thermodynamically stable thienyllithium, which underwent Negishi coupling to provide the corresponding 2-arylated 3,5-dibromothiophenes in one pot. The resultant beta-bromo group was much less reactive than the remaining alpha-bromo group, enabling facile synthesis of multiply arylated thiophenes. In addition to the scope of this reaction, its synthetic utility of the one-pot halogen dance/Negishi coupling is demonstrated by the syntheses of thiophene-fused indoles and other pyrrole alkaloids.

  SOC SYNTHETIC ORGANIC CHEM JPN, Oct. 2020, JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 78(10) (10), 930 - 942, Japanese

  [Refereed]


• Convergent Total Synthesis of Lamellarins and Their Congeners

  Daiki Morikawa, Kazuki Morii, Yuto Yasuda, Atsunori Mori, Kentaro Okano

  A convergent total synthesis of lamellarins S and Z is described. The synthesis features a halogen dance of an easily accessible alpha,beta-dibromopyrrole promoted by an ester moiety. The resultant beta,beta'-dibromopyrrole undergoes a ligand-controlled Suzuki-Miyaura coupling to provide a range of diarylated pyrrole derivatives. The established synthetic method was also applicable to the synthesis of ningalin B and lukianols A and B.

  Corresponding, AMER CHEMICAL SOC, Jul. 2020, JOURNAL OF ORGANIC CHEMISTRY, 85(13) (13), 8603 - 8617, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Steric effects on deprotonative generation of cyclohexynes and 1,2-cyclohexadienes from cyclohexenyl triflates by magnesium amides

  Yuto Hioki, Atsunori Mori, Kentaro Okano

  Steric effects on the deprotonative generation of cyclohexynes and 1,2-cyclohexadienes from cyclohexenyl triflates are described. A cyclohexenyl triflate, which is readily available from nonsubstituted cyclohexanone, was selectively converted to cyclohexyne using magnesium bis(2,2,6,6-tetramethylpiperidide) as base. The generated cyclohexyne was trapped by 1,3-diphenylisobenzofuran to afford the cycloadduct. This method was also applied to a benzo-fused cyclohexenyl triflate prepared from alpha-tetralone. A cyclohexenyl triflate bearing two methyl substituents at the 3-position was selectively transformed into the corresponding 1,2-cyclohexadiene. This 1,2-cyclohexadiene reacted with 1,3-diphenylisobenzofuran, styrene, and nitrone to provide the corresponding cycloadducts in good yields. (C) 2020 Elsevier Ltd. All rights reserved.

  PERGAMON-ELSEVIER SCIENCE LTD, May 2020, TETRAHEDRON, 76(22) (22), English

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Thermally Induced Self-Doping of π-Conjugated Polymers Bearing a Pendant Neopentyl Sulfonate Group

  Atsunori Mori, Chihiro Kubota, Keisuke Fujita, Masayasu Hayashi, Tadayuki Ogura, Toyoko Suzuki, Kentaro Okano, Masahiro Funahashi, Masaki Horie

  Feb. 2020, Macromolecules, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• One-Pot Deprotonative Synthesis of Biarylazacyclooctynones

  Yuto Hioki, Mayu Itoh, Atsunori Mori, Kentaro Okano

  © 2020 Georg Thieme Verlag. All rights reserved. Deprotonative formation of biarylazacyclooctynone (BARAC) from the corresponding enol triflate is described. The reaction furnished the azacyclooctynone within one hour at -78 °C. This process could be performed in one pot from the starting ketone to provide a range of BARAC derivatives in moderate to excellent yields. The protocol enabled the gram-scale formation of the BARAC skeleton by reducing the number of reaction steps. Furthermore, the established method was applied to the synthesis of the BARAC derivative bearing a coumarin moiety.

  Corresponding, 2020, Synlett, 31(2) (2), 189 - 193, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Formation of seven-membered-ring fused bithiophene derivatives by nosyl annulation

  Atsunori Mori, Masayasu Hayashi, Mitsuru Matsuoka, Shiomi Ashida, Yukiko Ito, Kohei Hosokawa, Toyoko Suzuki, Kentaro Okano, Chi Hsien Wang, Masaki Horie

  © 2020 The Japan Institute of Heterocyclic Chemistry. Nosyl annulation of a bithiophene derivative with nosylamide (NsNH2) gives a 5-7-5 fused N, S-heterocyclic compound. The detailed molecular structure of the obtained nosylamide was analyzed by single-crystal X-ray crystallography. The obtained product was transformed into several amines and amides. The C-Br bond at the fused heterocycle was also subjected to cross-coupling reactions, where the nosyl group was found to be tolerant.

  2020, Heterocycles, 101(2) (2), 461 - 470, English

  [Refereed][Invited]

  Scientific journal


• A formal preparation of regioregular and alternating thiophene−thiophene copolymers bearing different substituents

  Atsunori Mori, Keisuke Fujita, Chihiro Kubota, Toyoko Suzuki, Kentaro Okano, Takuya Matsumoto, Takashi Nishino, Masaki Horie

  Differently substituted thiophene−thiophene alternating copolymer was formally synthesized employing a halobithiophene as a monomer. Nickel-catalyzed polymerization of bithiophene, which substituent at the 3-position involves alkyl, fluoroalkyl, or oligosiloxane containing alkyl group, afforded the corresponding copolymer in good to excellent yield. The solubility test to organic solvents was performed to reveal several copolymers show a superior solubility. X-ray diffraction analysis of the thin film of the alternating copolymer composed of methyl and branched oligosiloxane substituents was also performed and found that the film suggested formation of dual-layered structure.

  Beilstein Institut, Dec. 2019, Beilstein journal of organic chemistry, 16, 317 - 324, English, International magazine

  [Refereed]

  Scientific journal


• Computational Studies on the Racemication Barriers of Winding Vine-Shaped Heterobiaryls with Molecular Asymmetry

  MORI ATSUNORI, ASHIDA SHIOMI, ITO YUKIKO, CHENG JIAQIANG, SUZUKI TOYOKO, OKANO KENTARO, HASHIMOTO TAKAYOSHI

  DFT calculation studies were performed for the estimation of racemization barrier of winding vine-shaped heterobiaryls showing molecular asymmetry. The calculated value showed good agreement compared with that derived from experimental studies. Effects of hetroaromatic structure, carbon-carbon double bond at the winding-vine moiety, substituent at the double bond, and substituent at the heteroaromatic rings were studied.

  PERGAMON-ELSEVIER SCIENCE LTD, Aug. 2019, Heterocycles, 99(1) (1), 294 - 300, English

  [Refereed]

  Scientific journal


• Unprecedented Regioregular Poly(1,4‐arylene)s Prepared by Nickel(II)‐Catalyzed Cross‐Coupling Polymerization of 2,5‐Disubstituted Bromo(chloro)arylene

  Yushin Shibuya, Naoki Nakagawa, Naoki Miyagawa, Toyoko Suzuki, Kentaro Okano, Atsunori Mori

  Wiley, Jul. 2019, Angewandte Chemie, 131(28) (28), 9647 - 9650

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Unprecedented regioregular poly(1,4-arylene)s prepared by nickel(II)-catalyzed cross-coupling polymerization of 2,5-disubstituted bromo(chloro)arylene

  SHIBUYA YUSHIN, MIYAGAQA NAOKI, NAKAGAWA NAOKI, SUZUKI TOYOKO, OKANO KENTARO, MORI ATSUNORI

  The unprecedented synthesis of regioregular head-to-tail-type poly(1,4-arylene)s bearing different substituents at the 2- and 5-positions is described. They were prepared by the polymerization of 2,5-disubstituted bromo(chloro)arylenes by selective halogen-metal exchange with a Grignard reagent and subsequent cross-coupling polymerization with a nickel catalyst [NiCl2(dppp)]. Formation of the regioregular poly(1,4-arylene)s were confirmed by NMR spectroscopy, and showed remarkable differences to those polymers having uncontrolled regioregularity. Polymerization of bromo(chloro)arylenes with a chiral alkoxy substituent also led to the regioregular head-to-tail-type polyarylene, which demonstrated circular dichroism, thus suggesting formation of a structure with higher-order regularity.

  Wiley, Jul. 2019, Angewante Chemie International Edition, 58(28) (28), 9547 - 9550, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Synthesis and Properties of Regioregular Polythiophene bearing Cyclic Siloxane Moiety at the Side Chain and the Formation of Polysiloxane Gel by the Acid Treatment on the Thin Film

  OGURA TADAYUKI, KUBOTA CHIHIRO, SUZUKI TOYOKO, OKANO KENTARO, TANAKA NORIKAZU, MATSUMOTO TAKUYA, NISHINO TAKASHI, MORI ATSUNORI, OKITA TAKUMI, FUNAHASHI MASAHIRO

  Preparation of 2-halo-3-substituted-thiophene bearing a cyclic oligosiloxane moiety in the side chain was carried out and subjected to nickel(II)-catalyzed deprotonative polymerization to give the corresponding polythiophene, which was found to be highly soluble in various organic solvents particularly in hexanes. Treatment of the thin film of the obtained polythiophene with acidic vapor resulted in cross linking of the cyclic siloxane moiety through ring opening. Accompanying doping of the polythiophene main chain on the polymer film indicated improved conductivity with remarkably drastic change in before/after acidic treatment.

  日本化学会, Jun. 2019, Chemistry Letters, 48(6) (6), 611 - 614, English

  [Refereed]

  Scientific journal


• Synthetic Studies on Plakinidines

  T. Satoh, T. Adachi, K. Okano, J. Sakata, H. Tokuyama

  2019, Heterocycles, 99, 310 - 323, English

  [Refereed]

  Scientific journal


• Total Synthesis of (+)-CC-1065 Utilizing Ring Expansion Reaction of Benzocyclobutenone Oxime Sulfonate

  T. Imaizumi, Y. Yamashita, Y. Nakazawa, K. Okano, J. Sakata, H. Tokuyama

  2019, Organic Letters, 21, English

  [Refereed]

  Scientific journal


• Practical Synthesis of Precursors of Cyclohexyne and 1,2-Cyclohexadiene

  Ryo Nakura, Kazuki Inoue, Kentaro Okano, Atsunori Mori

  © Georg Thieme Verlag Stuttgart. New York. This study investigated a practical method for regiocontrolled synthesis of precursors of strained cyclohexynes and 1,2-cyclohexadienes, which is a one-pot procedure consisting of a rearrangement of silyl enol ether and subsequent formation of the enol triflates. Triethylsilyl enol ether, derived from cyclohexanone, was treated with a combination of LDA and t -BuOK in n -hexane/THF to encourage the migration of the silyl group to generate an α-silyl enolate. Subsequently, the α-silyl enolate was reacted with Comins' reagent to yield the corresponding enol triflate. Finally, the α-silylated trisubstituted lithium enolate for the synthesis of 1,2-cyclohexadiene precursor was isomerized in the presence of a stoichiometric amount of water for one hour at room temperature to exclusively provide tetrasubstituted lithium enolate for the synthesis of cyclohexyne precursor in one pot.

  2019, Synthesis (Germany), 51(7) (7), 1561 - 1564

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Synthesis of 4,4-dimethyl-2-(2-pyrrolyl)-2-oxazolines

  Kentaro Okano, Kazuki Morii, Daichi Mari, Atsunori Mori

  © 2019 The Japan Institute of Heterocyclic Chemistry – A practical synthesis of 4,4-dimethyl-2-oxazolines on pyrrole was achieved via the cyclization of the corresponding amides, which were derived from the trichloroacetylpyrroles. The established conditions were applicable to pyrroles bearing a ketone or an ester moiety. In addition to pyrroles, the method could be extended to the synthesis of the indole derivative.

  2019, Heterocycles, 98(1) (1), 63 - 77

  [Refereed]

  Scientific journal


• Synthesis of furan-fused silole and phosphole by one-pot halogen dance/homocoupling of bromofurfural derivative

  Kentaro Okano, Yuki Murase, Atsunori Mori

  © 2019 The Japan Institute of Heterocyclic Chemistry. Synthesis of a furan-fused silole and phosphole was achieved through a one-pot halogen dance/homocoupling of a bromofurfural derivative followed by the formation of the silole and phosphole skeleton.

  2019, Heterocycles, 99(2) (2), 1444 - 1451

  [Refereed]

  Scientific journal


• Nosyl (2-nitrobenzenesulfonyl) annulation strategy toward winding vine-shaped bithiophenes

  ASHIDA SHIOMI, TANAKA NAOKI, ITO YUKIKO, MATSUOKA MITSURU, HASHIMOTO TAKAYOSHI, OKANO KENTARO, MIYAZAKI YUJI, KOBAYASHI TOHRU, YAITA TSUYOSHI, MORI ATSUNORI

  Winding vine-shaped bithiophene was synthesized through the nosyl (2-nitrobenzenesulfonyl) cyclization protocol. The reaction of bithiophene bearing bromomethyl groups at the 3,3'-positions with nosylated 1,2-ethylenediamine in the presence of potassium carbonate afforded the annulated product in excellent yield. The obtained bithiophene was found to contain a 10-membered ring, which was confirmed by X-ray analysis. The related nosyldiamine bearing a tri- or tetramethylene group also reacted in a similar manner, affording an 11- or 12-membered macrocycle, respectively.

  American Chemical Society, Dec. 2018, Journal of Organic Chemistry, 83(23) (23), 14797–14801 - 14801, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Chirality recognition of winding vine-shaped heterobiaryls with molecular asymmetry. Kinetic and dynamic kinetic resolution by Shi's asymmetric epoxidation

  Kazuki Maruhashi, Yoichi Okayama, Ryo Inoue, Shiomi Ashida, Yuka Toyomori, Kentaro Okano, Atsunori Mori

  The chirality of winding vine-shaped heterobiaryls with molecular asymmetry is recognized by a sugar-based chiral oxidant. Kinetic resolution of (±)-bisbenzoimidazole bearing an olefin moiety takes place with Shi's asymmetric epoxidation to observe k rel value up to ca. 35 affording the corresponding epoxide. The reaction of a (±)-bithiophene derivative also recognized the chirality to give the corresponding epoxide with er of 96:4 at 39% conversion. Dynamic kinetic resolution is found to take place when unsymmetrical biaryl composed of benzoimidazole/thiophene is subjected to Shi's epoxidation, whose conversion of the racemic substrate exceeds to 50%.

  Nature Publishing Group, Dec. 2018, Scientific Reports, 8(1) (1), English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Regiocontrolled Halogen Dance of Bromothiophenes and Bromofurans

  Mari Daichi, Miyagawa Naoki, Okano Kentaro, Mori Atsunori

  The LDA (lithium diisopropylamide)-promoted regiocontrolled halogen dance of alpha-bromothiophenes and alpha-bromofurans is described. Bromothiophenes bearing a diethyl acetal moiety undergo selective deprotonation at the beta-position adjacent to the bromo group. In contrast, oxazoline, ester, and amide groups act as directing groups in the initial lithiation step to generate a carbanion at the beta-position neighboring the directing group to exclusively give the other regioisomer. These results can be applied to the regiocontrolled halogen dance of bromofuran derivatives.

  AMER CHEMICAL SOC, Nov. 2018, JOURNAL OF ORGANIC CHEMISTRY, 83(22) (22), 14126 - 14137, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Revisiting of Benzophenone Ketyl Still: Use of a Sodium Dispersion for the Preparation of Anhydrous Solvents

  Inoue Ryo, Yamaguchi Mana, Murakami Yoshiaki, Okano Kentaro, Mori Atsunori

  A facile generation of organic solvents of anhydrous grade can be Performed by distillation from sodium benzophenone ketyl, which is prepared from commercial sodium dispersion and benzophenone. The distilled tetrahydrofuran, diethyl ether, hexane, 1,2-dimethoxy-ethane, and 14-dioxane with water contents less than 10 ppm were obtained by a simple protocol. Safe treatment of the distillation residue also was simply achieved by the addition of methanol. The protocol suits for providing a small amount of an anhydrous solvent at the laboratory scale.

  AMER CHEMICAL SOC, Oct. 2018, ACS OMEGA, 3(10) (10), 12703 - 12706, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• One-Pot Reductive Allylation of Amides by Using a Combination of Titanium Hydride and an Allylzinc Reagent: Application to a Total Synthesis of (-)-Castoramine

  Itabashi Suguru, Shimomura Masashi, Sato Manabu, Azuma Hiroki, Okano Kentaro, Sakata Juri, Tokuyama Hidetoshi

  Aug. 2018, SYNLETT, 29(13) (13), 1786 - 1790

  [Refereed]


• Synthesis of furan dimer-based polyamides with a high melting point

  Naoki Miyagawa, Toyoko Suzuki, Kentaro Okano, Takuya Matsumoto, Takashi Nishino, Atsunori Mori

  Polyamide composed of furan dimer, which is prepared from biomass-derived organic molecule 2-furfural, is synthesized. The reaction of 2,2′-furan dimer 5,5′-dicarbonyl chloride with several 1,ω-diamines was carried out with a solution or interfacial polycondensation leading to the corresponding polyamide. Measurement of the melting point was performed resulting to exhibit a higher temperature compared with the related polyamide bearing a single furan ring composed of furan-2,5-dicarboxylic acid (FDCA). Thermal analyses (TG–DTA) also indicated higher temperatures of decomposition than those of FDCA-derived polyamide. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1516–1519.

  John Wiley and Sons Inc., Jul. 2018, Journal of Polymer Science, Part A: Polymer Chemistry, 56(14) (14), 1516 - 1519, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• One-Pot Synthesis of Silylated Enol Triflates from Silyl Enol Ethers for Cyclohexynes and 1,2-Cyclohexadienes

  Inoue Kazuki, Nakura Ryo, Okano Kentaro, Mori Atsunori

  Regiocontrolled synthesis of precursors for strained cyclohexynes and 1,2-cyclohexadienes is described based on one-pot rearrangement of silyl enol ether followed by formation of enol triflate. Treatment of silyl enol ether with a combination of LDA and tBuOK led to the migration of the silyl group to generate -silyl enolate, which was treated with Comins' reagent to provide the corresponding enol triflate. The transient -silylated lithium enolate was smoothly isomerized in the presence of stoichiometric amount of water within one hour at room temperature, providing precursors for cyclohexynes exclusively in one pot. Effects of silyl groups, isomerization of the lithium enolate, and regiocontrolled generation of these precursors for these strained molecules were also investigated.

  WILEY-V C H VERLAG GMBH, Jul. 2018, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2018(25) (25), 3343 - 3347, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Deprotonative Generation of Cyclohexynes from Cyclic Enol Triflates Using Aluminate Bases

  Hioki Yuto, Yukioka Taro, Okano Kentaro, Mori Atsunori

  Wiley, Jul. 2018, ASIAN JOURNAL OF ORGANIC CHEMISTRY, 7(7) (7), 1298 - 1301

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A Cell-Targeted Non-Cytotoxic Fluorescent Nanogel Thermometer Created with an Imidazolium-Containing Cationic Radical Initiator

  Seiichi Uchiyama, Toshikazu Tsuji, Kyoko Kawamoto, Kentaro Okano, Eiko Fukatsu, Takahiro Noro, Kumiko Ikado, Sayuri Yamada, Yuka Shibata, Teruyuki Hayashi, Noriko Inada, Masaru Kato, Hideki Koizumi, Hidetoshi Tokuyama

  A cationic fluorescent nanogel thermometer based on thermo-responsive N-isopropylacrylamide and environment-sensitive benzothiadiazole was developed with a new azo compound bearing imidazolium rings as the first cationic radical initiator. This cationic fluorescent nanogel thermometer showed an excellent ability to enter live mammalian cells in a short incubation period (10 min), a high sensitivity to temperature variations in live cells (temperature resolution of 0.02–0.84 °C in the range 20–40 °C), and remarkable non-cytotoxicity, which permitted ordinary cell proliferation and even differentiation of primary cultured cells.

  Wiley-VCH Verlag, May 2018, Angewandte Chemie - International Edition, 57(19) (19), 5413 - 5417, English

  [Refereed]

  Scientific journal


• Magnesium Bisamide-Mediated Halogen Dance of Bromothiophenes

  Yoshiki Yamane, Kazuhiro Sunahara, Kentaro Okano, Atsunori Mori

  A magnesium bisamide-mediated halogen dance of bromothiophenes is described. The thienylmagnesium species generated in situ is more stable than the corresponding thienyllithium species, which was applied to trap the transient anion species with several electrophiles, such as allyl iodide, phenyl isocyanate, and tributylstannyl chloride. The utility of the magnesium bisamide-mediated halogen dance is useful in the concise synthesis of a medicinally advantageous compound via a one-pot, ester-directed halogen dance/Negishi cross coupling.

  American Chemical Society, Mar. 2018, Organic Letters, 20(6) (6), 1688 - 1691, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Synthesis of 9,10-Diarylanthracenes via Mg(TMP) 2 ·2LiCl-Mediated Benzyne Generation/[4+2] Cycloaddition and Deoxygenation of 9,10-Epoxyanthracene Intermediates

  Naoya Miyamoto, Yuki Nakazawa, Takanori Nakamura, Kentaro Okano, Sota Sato, Zhe Sun, Hiroyuki Isobe, Hidetoshi Tokuyama

  A new synthetic route to functionalized 9,10-diarylanthracenes has been developed. 9,10-Epoxyanthracene intermediates were prepared by [4+2] cycloaddition of 1,3-diarylisobenzofuran with a variety of functionalized benzyne intermediates, which were obtained by Mg(TMP) 2 ·2LiCl-mediated benzyne generation. For the cleavage of the resultant 9,10-epoxyanthracene intermediates, we developed mild deoxygenation conditions using a combination of trifluoroacetic acid and Et 3 SiH. The utility of this sequence was demonstrated by application to the synthesis of 5,7,12,14-tetraphenylpentacene.

  Georg Thieme Verlag, Mar. 2018, Synlett, 29(4) (4), 513 - 518, English

  [Refereed]

  Scientific journal


• Synthesis of Thieno[3,2-b]indoles via Halogen Dance and Ligand-Controlled One-Pot Sequential Coupling Reaction

  Yuki Hayashi, Kentaro Okano, Atsunori Mori

  A two-pot synthesis of thieno[3,2-b]indole from 2,5-dibromothiophene is described. A halogen dance of 2,5-dibromothiophene was performed with LDA, and subsequent Negishi coupling was performed with 2-iodoaniline derivatives to provide the corresponding coupling products. The resulting two bromo groups have different reactivities, which were utilized for the one-pot Suzuki-Miyaura coupling/intramolecular Buchwald-Hartwig amination to produce thieno[3,2-b]indole via an assisted tandem catalysis that involved in situ ligand exchange.

  American Chemical Society, Feb. 2018, Organic Letters, 20(4) (4), 958 - 961, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Synthesis of phenol and paphthol from furfural derivatives

  Kentaro Okano, Yuki Murase, Naoki Miyagawa, Kana Ashida, Atsunori Mori

  Synthesis of phenol and naphthol derivatives was performed from furfural derivatives through cycloaddition with an alkyne and benzyne, respectively. Lewis acid-promoted ring opening of the cycloadducts led to the formation of the corresponding phenol and naphthol derivatives. Amide-directed C-H alkenylation and arylation gave functionalized pi-conjugated naphthalene derivatives.

  PERGAMON-ELSEVIER SCIENCE LTD, 2018, Heterocycles, 97(1) (1), 580 - 590, English

  [Refereed]

  Scientific journal


• Benzoxazole-Directed Halogen Dance of Bromofuran

  Naoki Miyagawa, Yuki Murase, Kentaro Okano, Atsunori Mori

  A halogen dance of a benzoxazole-conjugated bromofuran derived from furfural is described. The reaction proceeds through a benzoxazole-directed lithiation to provide the a-lithiofuran, which is subjected to Negishi coupling to give a-arylated benzoxazole-conjugated furan derivatives. The synthetic utility of the reaction was demonstrated by transformation of the residual bromo group into a side chain bearing a siloxane moiety, which resulted in a significant improvement in solubility in organic solvents.

  GEORG THIEME VERLAG KG, Jun. 2017, SYNLETT, 28(9) (9), 1106 - 1110, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Polymerization of Furylthiazoles with Palladium-Catalyzed Direct Arylation Polycondensation

  Kana Ashida, Yuki Murase, Naoki Miyagawa, Kentaro Okano, Atsunori Mori

  Effective transformation of a biomass-derived heteroaromatic compound furfural into conjugated polymer is described. Furylthiazole composed of furan and thiazole rings is employed as a monomer and palladium-catalyzed C-H coupling polycondensation furnishes the corresponding formal alternating copolymer. The coupling reaction in the presence of Pd(OAc)(2) (20mol%) as a catalyst undergoes polymerization in >99% yield with M-n = 10.2 x 10(3).

  CHEMICAL SOC JAPAN, May 2017, BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 90(5) (5), 565 - 567, English

  [Refereed]

  Scientific journal


• Remarkable Reactivity Differences of Chlorothiophene and Chlorinated Oligothiophenes in NiCl2(PPh3)(2)-catalyzed Polymerization

  Naoki Nakagawa, Tadayuki Ogura, Keisuke Fujita, Yugo Sumino, Takayoshi Hashimoto, Kentaro Okano, Atsunori Mori

  A simple and ubiquitous nickel(II) complex NiCl2(PPh3)(2) catalyzes polymerization of oligothiophenes. Treatment of chlorobithiophene with chloromagnesium 2,2,6,6-tetramethyl-piperidin-1-yl lithium chloride salt (TMPMgCl center dot LiCl) followed by addition of 2.0 mol% NiCl2(PPh3)(2) undergoes deprotonative polymerization leading to poly(3-hexylthiophene) (P3HT) with M-n = 13000 and M-w/M-n = 1.67 (74% yield). The related terthiophene and quaterthiophene also polymerize to afford the corresponding polythiophene while little polymerization takes place with 2-chloro-3-hexylthiophene under similar conditions.

  CHEMICAL SOC JAPAN, Apr. 2017, CHEMISTRY LETTERS, 46(4) (4), 453 - 455, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A Step-Efficient Pathway to Chlorine-Functionalized Thiophene Oligomers by Palladium-Catalyzed Deprotonative Coupling of Chlorothiophenes

  Keisuke Fujita, Naoki Nakagawa, Kazuhiro Sunahara, Tadayuki Ogura, Kentaro Okano, Atsunori Mori

  Deprotonative metalation of 2-chloro-3-substituted thiophene at the 5-position of the thiophene ring is performed by using a bulky magnesium amide 2,2,6,6-tetramethylpiperidin-1-yl magnesium chloride lithium chloride salt (TMPMgCl.LiCl). The obtained metallic species reacts with bromothiophene to afford the regioregular headto- tail-type chlorobithiophene, which is subjected to further end functionalization by the coupling reaction with the C-Cl bond. Deprotonative C-H coupling polycondensation of substituted chlorobithiophene derivatives gives polythiophene as a formal alternating copolymer.

  GEORG THIEME VERLAG KG, Mar. 2017, SYNTHESIS-STUTTGART, 49(6) (6), 1285 - 1294, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Generation of cycloalkynes through deprotonation of cyclic enol triflates with magnesium bisamides

  Yuto Hioki, Kentaro Okano, Atsunori Mori

  Deprotonative generation of cyclohexynes, cycloheptynes, and cyclooctynes was achieved by controlling the reactivities of transient anionic species from the corresponding enol triflates with magnesium bis(2,2,6,6-tetramethylpiperidide) as a base. The starting enol triflates are readily obtained through triflation of the corresponding ketones, allowing direct access to the cycloalkynes.

  ROYAL SOC CHEMISTRY, Feb. 2017, CHEMICAL COMMUNICATIONS, 53(17) (17), 2614 - 2617, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Preparation of furan dimer-based biopolyester showing high melting points

  Naoki Miyagawa, Tadayuki Ogura, Kentaro Okano, Takuya Matsumoto, Takashi Nishino, Atsunori Mori

  Furan dimer diester was obtained by reductive or oxidative homocoupling of furan carboxylate derivatives in the presence of a nickel or palladium catalyst. Treatment of the obtained diester with 1,ω-diol in the presence of titanium alkoxide as a catalyst leads to the corresponding polyester in excellent yields. The obtained polymers show remarkably high melting points compared with the related polyesters composed of a single furan ring derived from furan-2,5-dicarboxylic acid (FDCA). Thermal properties of the furan dimer-derived polyesters are comparable with those of terephthalate polymers such as poly(ethylene terephthalate).

  Chemical Society of Japan, 2017, Chemistry Letters, 46(10) (10), 1535 - 1538, English

  [Refereed]

  Scientific journal


• Total Synthesis of (-)-Histrionicotoxin through a Stereoselective Radical Translocation-Cyclization Reaction

  Manabu Sato, Hiroki Azuma, Akihiro Daigaku, Sota Sato, Kiyosei Takasu, Kentaro Okano, Hidetoshi Tokuyama

  Stereoselective total syntheses of (-)-histrionicotoxin and (-)-histrionicotoxin 235A are described. The 1-azaspiro[5.5]undecane skeleton was constructed diastereoselectively by a radical translocation-cyclization reaction involving a chiral cyclic acetal; the use of tris( trimethylsilyl) silane was crucial for the high diastereoselectivity. The cyclization product was converted into (-)-histrionicotoxin 235A through a one-pot partial-reduction-allylation reaction of a derivative containing an unprotected lactam. Finally, two terminal alkenes were transformed into enynes with the 1,3-amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (-)-histrionicotoxin.

  WILEY-V C H VERLAG GMBH, Jan. 2017, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 56(4) (4), 1087 - 1091, English

  [Refereed]

  Scientific journal


• Structural Determination of (-)-SCH 64874 and Hirsutellomycin by Semisynthesis

  Hidetoshi Tokuyama, Kaori Yamada, Hideto Fujiwara, Juri Sakata, Kentaro Okano, Malipan Sappan, Masahiko Isaka

  The structure of a C-2-syminetric epidithiodike-topiperazine alkaloid, SCH 64874, was determined by semisynthesis. The relative stereochemistry of the beta-hydroxy carboxylic acid chain having, three chiral centers was determined by comparison of the NMR data of the four possible diastereomeric beta-hydroxy carboxylic acid fragments with those of SCH 64874. Condensation of the (-)-deacetylaranotin core with two enantiomeric beta-hydroxy carboxylic acids revealed the relative stereochemistry of SCH 64874. The relative stereochemistry of the beta-keto carboxylic acid chain of the analogous alkaloid hirsutellomycin was determined in a stepwise manner. The C4'-C6' syn relationships were predicted by comparing the NMR data of the corresponding ester fragments with that of hirsutellomycin. The relative stereochemistry of the whole molecule, including the epimerizable C2' stereoeenter, was determined by introduction of four possible side chains into the bisdethiodi(methylthio)deacetylaranotin core. We found that the stereochemistry of CZ' converged with that of the thermodynamically stable form influenced by the core structure.

  AMER CHEMICAL SOC, Jan. 2017, JOURNAL OF ORGANIC CHEMISTRY, 82(1) (1), 353 - 371, English

  [Refereed]

  Scientific journal


• SYNTHESIS OF UNSYMMETRICAL HETEROBIARYLS WITH WINDING VINE-SHAPED MOLECULAR ASYMMETRY THROUGH A CONDENSATION PATHWAY

  Atsunori Mori, Daichi Matsuoka, Shiomi Ashida, Ryo Inoue, Kazuki Maruhashi, Yoichi Okayama, Guan Hong Jin, Kentaro Okano

  Oxidative condensation of N-(3-buten-1-yl)-1,2-phenylenediamine with a formylated heteroarene bearing 3-buten-1-yl substituent gives unsymmetrical heterobiaryl in 42-86% yields. Ring-closing metathesis of the thus obtained product affords the cyclized product, which resulted in separation of each enantiomer by HPLC with a chiral column showing molecular asymmetry.

  PERGAMON-ELSEVIER SCIENCE LTD, Jan. 2017, HETEROCYCLES, 95(1) (1), 268 - 276, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• One-Pot Halogen Dance/Negishi Coupling of Dibromothiophenes for Regiocontrolled Synthesis of Multiply Arylated Thiophenes

  Kentaro Okano, Kazuhiro Sunahara, Yoshiki Yamane, Yuki Hayashi, Atsunori Mori

  One-pot halogen dance/Negishi cross-coupling of readily available 2,5-dibromothiophenes is described. A lithium diisopropylamide (LDA)-mediated halogen dance reaction resulted in the formation of thermodynamically stable -lithiodibromothiophenes, which were transmetalated with ZnCl2 and subjected to Negishi cross-coupling to provide the corresponding arylated dibromothiophenes in one pot. The resultant -bromo group was much less reactive than the remaining -bromo group, which was used in a one-pot double Suzuki-Miyaura cross-coupling, enabling facile synthesis of multiply arylated thiophenes.

  WILEY-V C H VERLAG GMBH, Nov. 2016, CHEMISTRY-A EUROPEAN JOURNAL, 22(46) (46), 16450 - 16454, English

  [Refereed]

  Scientific journal


• SYNTHESIS OF FURAN-OXAZOLE CONJUGATED FLUORESCENT MATERIALS FROM BIOMASS-DERIVED FURFURAL THROUGH CROSS-COUPLING REACTIONS

  Yuki Murase, Kana Ashida, Shota Tanaka, Kentaro Okano, Atsunori Mori

  Synthesis of furyloxazole was performed from biomass-derived furfural and senile methyl ester through dehydrative condensation and oxidation in one pot. Bromination and subsequent palladium-catalyzed arylation with arylboronates proceeded smoothly at the furan ring to provide arylated furylthiazoles. Arylation of C-H bond at the 5 position of the oxazole ring under Fagnou's conditions led to formation of diarylated furyloxazoles, which exhibit higher quantum yields over those of the related furylthiazole derivatives.

  PERGAMON-ELSEVIER SCIENCE LTD, Apr. 2016, HETEROCYCLES, 93(1) (1), 140 - 149, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Synthetic Studies on Acochlearine: Construction of the A/B/C/E/F Ring System

  Kosuke Fujioka, Naoya Miyamoto, Hiroki Toya, Kentaro Okano, Hidetoshi Tokuyama

  Synthetic studies on acochlearine are described. The pentacyclic A/B/C/E/F ring system of acochlearine was constructed from a bicyclic enone via chemoselective reductive amination, one-pot bromination-intramolecular Mannich reaction cascade, and 6-electrocyclization.

  GEORG THIEME VERLAG KG, Mar. 2016, SYNLETT, 27(4) (4), 621 - 625, English

  [Refereed]

  Scientific journal


• Trichloroboron-promoted deprotection of phenolic benzyl ether using pentamethylbenzene as a non Lewis-basic cation scavenger

  Shun Okaya, Keiichiro Okuyama, Kentaro Okano, Hidetoshi Tokuyama

  Wiley Blackwell, 2016, Organic Syntheses, 93, 63 - 74, English

  [Refereed]

  Scientific journal


• Total Synthesis of (+)-MPC1001B

  Taichi Kurogi, Shun Okaya, Hideto Fujiwara, Kentaro Okano, Hidetoshi Tokuyama

  The first total synthesis of an epidithiodiketopiperazine alkaloid, (+)-MPC1001B, was accomplished. This synthesis features a tetra-n-butylammonium fluoride mediated intramolecular aldol reaction for forming the 15-membered macrolactone ring, and the construction of an epidithiodiketopiperazine substructure through a stepwise sulfenylation reaction involving a novel trityl trisulfide (TrSSS)-group transfer.

  WILEY-V C H VERLAG GMBH, Jan. 2016, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 55(1) (1), 283 - 287, English

  [Refereed]

  Scientific journal


• DIBALH-Mediated Reductive Ring-Expansion Reaction of Cyclic Ketoxime

  IMAIZUMI Taku, OKANO Kentaro, TOKUYAMA Hidetoshi

  2016, Org. Synth., 93, 1 - 13, English

  [Refereed]

  Scientific journal


• A concise total synthesis of (-)-indolactam V

  Toshiharu Noji, Kentaro Okano, Hidetoshi Tokuyama

  One-pot synthesis of tryptophanol derivative from N-Boc-aziridine and indole has been developed. The ring opening reaction of the aziridine takes place smoothly at -30 degrees C in a regioselective manner and tolerates a wide range of functional groups including halogens attached to the aromatic ring, which was also performed on a gram scale. The resulting tryptophanol derivative was converted to (-)-indolactam V from commercially available 4-bromoindole through a copper-mediated aryl amination in nine steps with an overall yield of 32%. (C) 2015 Elsevier Ltd. All rights reserved.

  PERGAMON-ELSEVIER SCIENCE LTD, Jun. 2015, TETRAHEDRON, 71(23) (23), 3833 - 3837, English

  [Refereed]

  Scientific journal


• Synthetic studies toward penitrem E: enantiocontrolled construction of B-E rings

  Yu Yoshii, Takanori Otsu, Norihiko Hosokawa, Kiyosei Takasu, Kentaro Okano, Hidetoshi Tokuyama

  Enantiocontrolled construction of B-E rings of penitrem E was accomplished from 4-iodoindole in 13 steps with an overall yield of 1.7%. Diastereoselective Tf2NH-catalyzed (2+2)-cycloaddition between silyl enol ether and methyl acrylate furnished a tetracyclic product possessing the characteristic cyclobutane ring bearing a hydroxyl group.

  ROYAL SOC CHEMISTRY, 2015, CHEMICAL COMMUNICATIONS, 51(6) (6), 1070 - 1073, English

  [Refereed]

  Scientific journal


• STEREOCHEMISTRY OF VINYLOGOUS RUBOTTOM OXIDATION OF PROLINE-FUSED CYCLOHEXADIENOL SILYL ETHER

  Kentaro Okano, Shun Okaya, Taichi Kurogi, Hideto Fujiwara, Hidetoshi Tokuyama

  The steric effect of vinylogous Rubottom oxidation of proline-fused cyclohexadienol silyl ether was investigated. The facial selectivity in the oxidation is governed by a synergistic effect of the proximal ester and a protective group on the nitrogen.

  PERGAMON-ELSEVIER SCIENCE LTD, Jan. 2015, HETEROCYCLES, 90(2) (2), 1299 - 1308, English

  [Refereed]

  Scientific journal


• Total Synthesis of (-)-Haouamine B Pentaacetate and Structural Revision of Haouamine B

  Yuichi Momoi, Kei-ichiro Okuyama, Hiroki Toya, Kenji Sugimoto, Kentaro Okano, Hidetoshi Tokuyama

  The enantiocontrolled total synthesis of (-)-haouamine B pentaacetate was accomplished via an optically active indane-fused beta-lactam, which was prepared by a newly developed Friedel-Crafts reaction. Subsequent cleavage of the beta-lactam and an intramolecular McMurry coupling reaction provided the core indane-fused tetrahydropyridine, which led to the elucidation of the structure, as proposed by Trauner and Zubia.

  WILEY-V C H VERLAG GMBH, Nov. 2014, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 53(48) (48), 13215 - 13219, English

  [Refereed]

  Scientific journal


• Stereocontrolled total synthesis and biological evaluation of (-)- and (+)-petrosin and its derivatives

  Hiroki Toya, Takahito Satoh, Kentaro Okano, Kiyosei Takasu, Masataka Ihara, Atsushi Takahashi, Haruo Tanaka, Hidetoshi Tokuyama

  Total synthesis of (-)- and (+)-petrosin was accomplished. Stereocontrolled construction of the quinolizidine ring was achieved through a diastereoselective Mannich reaction and an aza-Michael reaction. Head-to-tail dimerization was performed by assembly of the two monomers using Suzuki-Miyaura cross coupling and subsequent ring-closing metathesis to construct the 16-membered ring. Biological evaluation of synthetic (-)- and (+)-petrosin and its derivatives indicated that the bispiperidine structure was necessary for the inhibition of syncytium formation. (C) 2014 Elsevier Ltd. All rights reserved.

  PERGAMON-ELSEVIER SCIENCE LTD, Oct. 2014, TETRAHEDRON, 70(43) (43), 8129 - 8141, English

  [Refereed]

  Scientific journal


• Generation of Aryl Grignard Reagents from Arene Chromium Tricarbonyl Complexes by Mg(TMP)(2)center dot 2LiCl and Their Application to Murahashi Coupling

  Yuichi Momoi, Kentaro Okano, Hidetoshi Tokuyama

  A mild and straightforward synthesis of biaryls is described that is performed through direct arylation of the C-H bond of (arene) Cr(CO)(3) upon deprotonation with Mg(2,2,6,6-tetramethylpiperazide)(2)center dot 2LiCl and subsequent palladium-catalyzed cross-coupling reaction.

  GEORG THIEME VERLAG KG, Oct. 2014, SYNLETT, 25(17) (17), 2503 - 2507, English

  [Refereed]

  Scientific journal


• Synthesis of a Human Urate Transporter-1 Inhibitor, an Arginine Vasopressin Antagonist, and a 17 beta-Hydroxysteroid Dehydrogenase Type-3 Inhibitor, Using Ring-Expansion of Cyclic Ketoximes with DIBALH

  Hidetsura Cho, Yusuke Iwama, Kentaro Okano, Hidetoshi Tokuyama

  Synthesis of three clinical candidates for medicines, a human urate transporter-1 inhibitor, an arginine vasopressin antagonist, and a 17 beta-hydroxysteroid dehydrogenase type-3 inhibitor, is described. These compounds were synthesized via construction of their 3,4-dihydro-2H-benzo[b][1,4]oxazine, dibenzodiazepine, and dibenzazocine skeletons, respectively, using the reductive ring-expansion reaction of the corresponding bicyclic or tricyclic oximes with diisobutylaluminum hydride.

  PHARMACEUTICAL SOC JAPAN, Apr. 2014, CHEMICAL & PHARMACEUTICAL BULLETIN, 62(4) (4), 354 - 363, English

  [Refereed]

  Scientific journal


• FORMATION OF XANTHONE OXIME AND RELATED COMPOUNDS USING A COMBINATION OF tert-BUTYL NITRITE AND POTASSIUM HEXAMETHYLDISILAZIDE

  Yusuke Iwama, Takahiro Noro, Kentaro Okano, Hidetsura Cho, Hidetoshi Tokuyama

  Synthesis of xanthone oxime and related compounds via nitrosation of the dibenzylic position using a combination of tert-butyl nitrite and potassium hexamethyldisilazide is described. The reaction conditions are effective for the synthesis of xanthone oxime as well as thioxanthone, acridone, and anthrone oximes, which have been difficult to synthesize from the corresponding ketones by conventional dehydrative condensation with hydroxylamine.

  PERGAMON-ELSEVIER SCIENCE LTD, Jan. 2014, HETEROCYCLES, 88(2) (2), 1433 - 1444, English

  [Refereed]

  Scientific journal


• Total synthesis of PDE-I and -II by copper-mediated double aryl amination This paper is dedicated to Professor Teruaki Mukaiyama in celebration of the 40th anniversary of the Mukaiyama aldol reaction

  Kentaro Okano, Nakako Mitsuhashi, Hidetoshi Tokuyama

  A concise total synthesis of PDE-I and -II featuring copper-mediated double aryl amination with the combination of CuI, CsOAc, and Cs2CO 3 is described. The highly substituted pyrroloindole skeleton was constructed by a one-pot five-step sequence including double aryl amination, β-elimination, deprotection of a Cbz group, and unexpected formation of an indole via removal of an Ns group followed by rearomatization. The undesired elimination of the protecting group (Ns group) was hampered by using the Boc group as a protecting group in the second-generation synthesis, which excluded the reduction of the indole required in the first-generation synthesis. © 2013 Elsevier Ltd. All rights reserved.

  Dec. 2013, Tetrahedron, 69(51) (51), 10946 - 10954, English

  [Refereed]

  Scientific journal


• Formal Synthesis of Hepatitis C Virus NS5B Polymerase Inhibitor

  Takahiro Noro, Kentaro Okano, Hidetoshi Tokuyama

  A formal synthesis of a hepatitis C virus (HCV) inhibitor is described. The synthesis features a benzyne-mediated one-pot indoline formation-methylation sequence and an In(OTf)(3)-mediated mild oxa-Pictet-Spengler reaction for the synthesis of substituted electron-rich pyranoindole.

  GEORG THIEME VERLAG KG, Oct. 2013, SYNLETT, 24(16) (16), 2143 - 2147, English

  [Refereed]

  Scientific journal


• Enantiocontrolled Total Synthesis of (-)-Mersicarpine

  Yusuke Iwama, Kentaro Okano, Kenji Sugimoto, Hidetoshi Tokuyama

  A racemic synthesis of mersicarpine (1) was achieved by the Mizoroki-Heck reaction and a DIBALH-mediated reductive ring-expansion reaction. Based on a first-generation synthesis, a second-generation enantiocontrolled total synthesis of (-)-mersicarpine (1) was achieved by an 8-pot/11-step sequence in 21% overall yield from commercially available 2-ethylcyclohexanone. Subjection of a ketoester, which was prepared by an asymmetric Michael addition (according to the protocol by d'Angelo and Desmaele), and phenylhydrazine to modified Fischer indole conditions provided a six-membered tricyclic indole. Benzylic oxidation and subsequent oxime formation provided a ketoxime, which was treated with diisobutylaluminum hydride (DIBALH) to construct the characteristic azepinoindole skeleton in good yield. In the DIBALH-mediated reductive ring-expansion reaction, gradually increasing the reaction temperature and in situ-protection of the nitrogen in an oxygen-sensitive azepinoindole with a benzyloxycarbonyl (Cbz) group were crucial for the high-yielding process. With these methodologies, the short-step and efficient synthesis of (-)-mersicarpine was accomplished. Several synthetic efforts are also described.

  WILEY-V C H VERLAG GMBH, Jul. 2013, CHEMISTRY-A EUROPEAN JOURNAL, 19(28) (28), 9325 - 9334, English

  [Refereed]

  Scientific journal


• Synthesis of Substituted Indoline and Carbazole by Benzyne-Mediated Cyclization-Functionalization

  Toshiharu Noji, Hideto Fujiwara, Kentaro Okano, Hidetoshi Tokuyama

  A benzyne-mediated synthesis of substituted indolines and carbazoles was developed. The reaction includes generation of benzyne using Mg(TMP)(2)center dot 2LiCl as a base, cyclization, and trapping the resulting organomagnesium intermediate with an electrophile to provide a series of substituted indolines and carbazoles in a regiospecific manner. This was applied to a concise five-pot total synthesis of heptaphylline.

  AMER CHEMICAL SOC, Apr. 2013, ORGANIC LETTERS, 15(8) (8), 1946 - 1949, English

  [Refereed]

  Scientific journal


• Construction of Dibenzazocine Skeleton by Regiocontrolled Ring-Expansion Reaction of Cyclic Oxime with DIBAL-H: Facile Synthesis of 17 beta-Hydroxysteroid Dehydrogenase Type 3 Inhibitor

  Hidetsura Cho, Yusuke Iwama, Kentaro Okano, Hidetoshi Tokuyama

  Synthetic studies on a 17 beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) inhibitor are described. The unsymmetrical dibenzazocine skeleton was constructed by a regiocontrolled ring-expansion reaction of a cyclic oxime with DIBAL-H.

  GEORG THIEME VERLAG KG, Apr. 2013, SYNLETT, 24(7) (7), 813 - 816, English

  Scientific journal


• Total synthesis of makaluvamine A/D, damirone B, batzelline C, makaluvone, and isobatzelline C featuring one-pot benzyne-mediated cyclization-functionalization

  Takashi Oshiyama, Takahito Satoh, Kentaro Okano, Hidetoshi Tokuyama

  Total synthesis of pyrroloquinoline alkaloids, such as makaluvamine AID, damirone B, batzelline C, makaluvone, and isobatzelline C, was achieved featuring a one-pot benzyne-mediated cyclization-functionalization reaction. The synthetic utility was demonstrated by the construction of the common pyrrolo[4,3,2-de]quinoline skeleton. (C) 2012 Elsevier Ltd. All rights reserved.

  PERGAMON-ELSEVIER SCIENCE LTD, Nov. 2012, TETRAHEDRON, 68(46) (46), 9376 - 9383, English

  Scientific journal


• Ring-Expansion Reaction of Oximes with Aluminum Reductants

  Hidetsura Cho, Yusuke Iwama, Nakako Mitsuhashi, Kenji Sugimoto, Kentaro Okano, Hidetoshi Tokuyama

  The ring-expansion reactions of heterocyclic ketoximes and carbocyclic ketoximes with several reductants such as AlHCl2, AlH3 (alane), LiAlH4, LiAlH((OBu)-Bu-t)(3), and (MeOCH2CH2O)(2)AlH2Na (Red-Al) were examined. Among reductants, AlHCl2 (LiAlH4:AlCl3 = 1:3) in cyclopentyl methyl ether (CPME) has been found to be a suitable reagent for the reaction, and the rearranged cyclic secondary amines were obtained in good to excellent yields.

  MDPI AG, Jun. 2012, MOLECULES, 17(6) (6), 7348 - 7355, English

  Scientific journal


• Concise Total Synthesis of (-)-Mersicarpine

  Yusuke Iwama, Kentaro Okano, Kenji Sugimoto, Hidetoshi Tokuyama

  A concise total synthesis of (-)-mersicarpine from a known cyclohexanone was accomplished. The azepinoindole core was constructed by a DIBAL-H-mediated reductive ring-expansion reaction of oxime.

  AMER CHEMICAL SOC, May 2012, ORGANIC LETTERS, 14(9) (9), 2320 - 2322, English

  [Refereed]

  Scientific journal


• Total synthesis of batzelline C and isobatzelline C

  Takashi Oshiyama, Takahito Satoh, Kentaro Okano, Hidetoshi Tokuyama

  The total synthesis of batzelline C and isobatzelline C was accomplished. The synthesis features the construction of the highly substituted pyrrolo[4,3,2-de] quinoline skeleton by a benzyne-mediated cyclization- functionalization sequence.

  ROYAL SOC CHEMISTRY, 2012, RSC ADVANCES, 2(12) (12), 5147 - 5149, English

  [Refereed]

  Scientific journal


• Total Synthesis of (-)-Acetylaranotin

  Hideto Fujiwara, Taichi Kurogi, Shun Okaya, Kentaro Okano, Hidetoshi Tokuyama

  WILEY-V C H VERLAG GMBH, 2012, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 51(52) (52), 13062 - 13065, English

  [Refereed]

  Scientific journal


• SYNTHETIC STUDIES ON PASPALINE: LEWIS ACID-MEDIATED SEQUENTIAL CONSTRUCTION OF A-E RING SKELETON

  Kentaro Okano, Yu Yoshii, Hidetoshi Tokuyama

  The common pentacyclic skeleton of indole diterpene alkaloids, paspaline and its derivatives was constructed by a sequential reaction. The appropriate choice of the protecting group on the indole nitrogen was critical for the formation of bis(methylthio)allylic alcohol, which then underwent sulfonium ion formation and intramolecular electrophilic C-C-bond formation at the indole 3-position.

  PERGAMON-ELSEVIER SCIENCE LTD, Jan. 2012, HETEROCYCLES, 84(2) (2), 1325 - 1334, English

  Scientific journal


• 43 Total Synthesis of Dictyodendrins A-E(Oral Presentation)

  Okano Kentaro, Fujiwara Hideto, Noji Toshiharu, Fukuyama Tohru, Tokuyama Hidetoshi

  Dictyodendrins (1-5) were isolated in 2003 by Fusetani and Matsunaga from the marine sponge Dictyodendrilla verongiformis. These compounds have found to be the first marine alkaloids which possess inhibitory activity against telomerase (100% inhibition at a concentration of 50 μg/mL). They have attracted considerable attention as synthetic targets not only due to their important biological activity, but also to the unique structure consisting of the highly substituted pyrrolo[2,3-c]carbazole core. Herein, we describe an efficient total synthesis of all the member of dictyodendrins 1-5 featuring a newly developed benzyne-mediated indoline formation-functionalization sequence using magnesium bisamide. From our unsuccessful initial approaches, we learned that regioselective introduction of the substituent at the 7-position after the construction of the indoline skeleton was a difficult task due to its sterically congested environment. At this juncture, we decided to develop a straightforward and regiochemically secured methodology based on benzyne chemistry. Among a variety of bases tested, Mg(TMP)_2-2LiBr was found to be superior for smooth indoline formation and subsequent coupling reaction to give the desired product 19 in excellent yield. The double functionalization methodology was also applied to synthesis of 7-substituted indolines. Having successfully constructed the desired indoline bearing p-anisyl group at 7-position by the efficient benzyne-mediated cyclization cross coupling sequence, we then converted it to pivotal indole 20 by removal of the Boc group, DDQ oxidation to indole, and attachment of p-anisylethyl group on the nitrogen. The installation of subunits on the indole 2-position for the synthesis of dictyodendrin A (1), B (2), and E (5) was successfully carried out. Construction of the tetracyclic core skeleton followed by protecting group manipulation yielded dictyodendrin A (1), B (2), and E (5). By application of the synthetic route, we also completed total synthesis of dictyodendrin C (3) and D (4). In conclusion, we have developed the unprecedented one-pot benzyne-mediated indoline formation-cross coupling sequence via transmetallation to a copper species. This methodology provides direct access to the highly substituted indoline, which would be applicable to various nitrogen-containing heterocyclic compounds. By utilization of our methodology, we have established a highly flexible synthetic route by the introduction of the peripheral segments on the pivotal indole intermediate in a modular fashion, which enabled us to synthesize dictyodendrins A-E(1-5) systematically.

  Symposium on the chemistry of natural products, Sep. 2011, Symposium on the Chemistry of Natural Products, symposium papers, (53) (53), 253 - 258, Japanese


• Synthesis of Acylsilanes by Palladium-catalyzed Cross-coupling Reaction of Thiol Esters and Silylzinc Chlorides

  Hiroki Azuma, Kentaro Okano, Hidetoshi Tokuyama

  An acylsilane synthesis by a Pd-catalyzed cross-coupling reaction of thiol esters and silylzinc chlorides was developed. S-Phenyl thiol esters with a variety of functional groups were converted to corresponding acylsilanes.

  CHEMICAL SOC JAPAN, Sep. 2011, CHEMISTRY LETTERS, 40(9) (9), 959 - 961, English

  [Refereed]

  Scientific journal


• Preparation of horner-wadsworth-emmons reagent: Methyl 2- benzyloxycarbonylamino-2-(dimethoxy-phosphinyl)acetate

  Hiroki Azuma, Kentaro Okano, Tohru Fukuyama, Hidetoshi Tokuyama

  Wiley Blackwell, Jul. 2011, Organic Syntheses, 88, 152 - 161, English

  [Refereed]

  Scientific journal


• An intramolecular amination of aryl halides with a combination of copper (I) iodide and cesium acetate: Preparation of 5,6-dimethoxyindole-1,2- dicarboxylic acid 1-benzyl ester 2-methyl ester

  Toshiharu Noji, Kentaro Okano, Tohru Fukuyama, Hidetoshi Tokuyama

  Wiley Blackwell, Jul. 2011, Organic Syntheses, 88, 388 - 397, English

  [Refereed]

  Scientific journal


• REGIOSPECIFIC REARRANGEMENT OF HYDROXYLAMINES TO SECONDARY AMINES USING DIISOBUTYLALUMINUM HYDRIDE

  Hidetsura Cho, Kenji Sugimoto, Yusuke Iwama, Nakako Mitsuhashi, Kentaro Okano, Hidetoshi Tokuyama

  A systematic investigation of a reductive ring-expansion reaction of N-monosubstituted hydroxylamines with diisobutylaluminum hydride (DIBALH) was carried out. The reaction regiospecifically provided a variety of bicyclic or tricyclic heterocycles or linear secondary amines containing nitrogen attached to an aromatic ring.

  PERGAMON-ELSEVIER SCIENCE LTD, Mar. 2011, HETEROCYCLES, 82(2) (2), 1633 - +, English

  Scientific journal


• Total Synthesis of Dictyodendrins A-E

  Hidetoshi Tokuyama, Kentaro Okano, Hideto Fujiwara, Toshiharu Noji, Tohru Fukuyama

  A highly efficient total synthesis of dictyodendrins A-E was accomplished. The synthesis features a novel benzyne-mediated one-pot indoline formation/cross-coupling sequence for the construction of a highly substituted key indoline intermediate. Peripheral substituents were introduced onto this intermediate in a modular fashion to complete the total synthesis of dictyodendrins A-E.

  WILEY-V C H VERLAG GMBH, Feb. 2011, CHEMISTRY-AN ASIAN JOURNAL, 6(2) (2), 560 - 572, English

  [Refereed]

  Scientific journal


• Synthetic Studies toward Haouamine B: Construction of Indenotetrahydropyridone Skeleton

  Kei-ichiro Okuyama, Yuichi Momoi, Kenji Sugimoto, Kentaro Okano, Hidetoshi Tokuyama

  Synthetic studies on haouamine B are described. The characteristic indenotetrahydropyridone skeleton was constructed by intramolecular Friedel-Crafts alkylation of mesyloxy beta-lactam derivative and intramolecular McMurry coupling as key processes.

  GEORG THIEME VERLAG KG, Jan. 2011, SYNLETT, 2011(1) (1), 73 - 76, English

  Scientific journal


• Enantioselective Total Synthesis of (-)- and (+)-Petrosin

  Hiroki Toya, Kentaro Okano, Kiyosei Takasu, Masataka Ihara, Atsushi Takahashi, Haruo Tanaka, Hidetoshi Tokuyama

  The enantioselective total synthesis of (-)- and (+)-petrosin is described. The union of two key segments was executed by Suzuki Miyaura coupling. The quinolizidine rings were stereoselectively constructed via a diastereoselective Mannich reaction and an aza-Michael reaction. The 16-membered ring was constructed by ring-closing metathesis with the second-generation Grubbs catalyst.

  AMER CHEMICAL SOC, Nov. 2010, ORGANIC LETTERS, 12(22) (22), 5196 - 5199, English

  [Refereed]

  Scientific journal


• Total Synthesis of (+/-)-Lepadiformine A via Radical Translocation-Cyclization Reaction

  Manabu Fujitani, Masami Tsuchiya, Kentaro Okano, Kiyosei Takasu, Masataka Ihara, Hidetoshi Tokuyama

  A total synthesis of (+/-)-lepadiformine A was accomplished through construction of the 1-azaspiro[4.5]decane skeleton by a sequential radical translocation-cyclization reaction.

  GEORG THIEME VERLAG KG, Mar. 2010, SYNLETT, (5) (5), 822 - 826, English

  Scientific journal


• Total synthesis of PDE-II by copper-mediated double amination

  Kentaro Okano, Nakako Mitsuhashi, Hidetoshi Tokuyama

  A concise total synthesis of PDE-II featuring copper-mediated double aryl amination with the combination of CuI, CsOAc, and Cs(2)CO(3) is described. The highly substituted pyrroloindole skeleton was constructed by a one-pot five-step sequence including double aryl amination, beta-elimination, deprotection of a Cbz group, and removal of an Ns group followed by rearomatization.

  ROYAL SOC CHEMISTRY, 2010, CHEMICAL COMMUNICATIONS, 46(15) (15), 2641 - 2643, English

  [Refereed]

  Scientific journal


• Total Synthesis of Dictyodendrin A and B

  Kentaro Okano, Hideto Fujiwara, Toshiharu Noji, Tohru Fukuyama, Hidetoshi Tokuyama

  WILEY-BLACKWELL, 2010, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 49(34) (34), 5925 - 5929, English

  [Refereed]

  Scientific journal


• ヨウ化銅を用いる芳香族アミノ化反応を基盤とした(+)-ヤタケマイシンの不斉全合成

  OKANO KENTARO

  Mar. 2009, 東京大学学位論文, English

  Doctoral thesis


• Protection of Diols with p-(tert-Butyldimethylsilyloxy)benzylidene Acetal and Its Deprotection: (4-((4R,5R)-4,5-Diphenyl-1,3-dioxolan-2-yl)phenoxy)(tert-butyl)dimethylsilane

  OSAJIMA Hiroyuki, OKANO Kentaro, TOKUYAMA Hidetoshi, FUKUYAMA Tohru

  2009, Org. Synth., 86, 130 - 140, English

  [Refereed]

  Scientific journal


• A mild inter- and intramolecular amination of aryl halides with a combination of CuI and CsOAc

  Tetsuji Kubo, Chiharu Katoh, Ken Yamada, Kentaro Okano, Hidetoshi Tokuyama, Tohru Fukuyama

  A unique combination of CuI and CsOAc was found to catalyze aryl amination under mild conditions. The reaction takes place at room temperature or at 90 degrees C with broad functional group compatibility. The intramolecular reaction was able to form five-, six-, and seven-membered rings with various protecting groups on the nitrogen atom. The scope of the intermolecular amination, as well as its applications to unsymmetrical N,N'-dialkylated phenylenediamines, was investigated. (C) 2008 Elsevier Ltd. All rights reserved.

  PERGAMON-ELSEVIER SCIENCE LTD, Dec. 2008, TETRAHEDRON, 64(49) (49), 11230 - 11236, English


• Mild debenzylation of aryl benzyl ether with BCl(3) in the presence of pentamethylbenzene as a non-Lewis-basic cation scavenger

  Kentaro Okano, Kei-ichiro Okuyama, Tohru Fukuyama, Hidetoshi Tokuyama

  Scope and limitations of the debenzylation conditions for aryl benzyl ether, which was developed during our synthetic studies on yatakemycin, were investigated. The chemoselective debenzylation proceeds at low temperature with a combination of BCl(3) and pentamethylbenzene as a cation scavenger in the presence of various functional groups.

  GEORG THIEME VERLAG KG, Aug. 2008, SYNLETT, (13) (13), 1977 - 1980, English

  [Refereed]

  Scientific journal


• Mild debenzylation of aryl benzyl ether with BCl(3) in the presence of pentamethylbenzene as a non-Lewis-basic cation scavenger

  Kentaro Okano, Kei-ichiro Okuyama, Tohru Fukuyama, Hidetoshi Tokuyama

  Scope and limitations of the debenzylation conditions for aryl benzyl ether, which was developed during our synthetic studies on yatakemycin, were investigated. The chemoselective debenzylation proceeds at low temperature with a combination of BCl(3) and pentamethylbenzene as a cation scavenger in the presence of various functional groups.

  GEORG THIEME VERLAG KG, Aug. 2008, SYNLETT, (13) (13), 1977 - 1980, English

  Scientific journal


• Total synthesis of (+)-yatakemycin

  Kentaro Okano, Hidetoshi Tokuyama, Tohru Fukuyama

  A convergent total synthesis of (+)-yatakemycin was accomplished by a 20-step sequence in 13 % overall yield. The regioselective ring opening of (S)-epichlorohydrin with a 2,6-dibromophenyllithium derivative enabled us to introduce a chiral carbon center, which was required for the stereoselective construction of the cyclopropane ring. The five aryl-nitrogen bonds in (+)-yatakemycin were constructed by a mild copper-mediated aryl amination that utilized the combination of CuI with CsOAc. The efficient and chemoselective debenzylation of aryl benzyl ether with BCl3 in the presence of pentamethylbenzene was developed. With these new methodologies, the subgram-scale synthesis of (+)-yatakemycin was achieved.

  WILEY-V C H VERLAG GMBH, 2008, CHEMISTRY-AN ASIAN JOURNAL, 3(2) (2), 296 - 309, English

  [Refereed]

  Scientific journal


• 30 Total Synthesis of (+)-Yatakemycin

  Okano Kentaro, Tokuyama Hidetoshi, Fukuyama Tohru

  (+)-Yatakemycin (1), which was isolated from a culture broth of Streptomyces sp. TP-A0356, is an antitumor antibiotic that has a characteristic dienone cyclopropane ring found in duocarmycins and CC-1065. Among them, 1 has been shown to exhibit the most potent activity, and therefore has attracted a great deal of attention. The first total synthesis along with the revision of its structure and determination of the absolute configuration has recently been reported by Boger and co-workers. Herein, we describe an efficient total synthesis of 1 utilizing our copper-mediated amination for the construction of all five aryl-nitrogen bonds, allowing us to conduct a sub-gram-scale preparation of 1 in 16% overall yield over 17 steps (longest linear steps from the known starting compound 6). Synthesis of the left segment 3 commenced with dibromination of 6. Removal of the TFA group, and subsequent oxidation provided dihydroisoquinoline 7, which was readily converted to the cyclization precursor 9. The first amination reaction of 9 afforded indoline 10 with retention of the other bromo group. After conversion to the dehydroamino ester 12, the second amination was performed to provide dihydropyrroloindole 13. The Ns group and benzyl ester in 13 were then converted to Fmoc group and a methanethiol ester, respectively. Finally, an Fmoc-directed, regioselective demethylation was performed with BCl_3 to furnish the left segment 3. Our amination also proved to be highly effective for the construction of the middle segment 4. Cleavage of (S)-epichlorohydrin (18) with 2,6-dibromophenyllithium species 17 provided chlorohydrin 19, which was then converted to amination precursor 21. The crucial aryl amination took place smoothly to give tetrahydroquinoline 22. After Mizoroki-Heck reaction with a dehydroalanine derivative 23 and removal of the nosyl group, bromo group was introduced regioselectively. The second amination reaction at the sterically hindered position was achieved by using a stoichiometric amount of CuI to furnish the middle segment 4. The right-hand segment 5 was also prepared in a straightforward manner by using the aryl amination strategy. Three segments thus obtained were assembled to complete the total synthesis. After coupling of the middle segment 4 with the right segment 5, TBS ether 32 was converted into the mesylate 33. Subsequent hydrolysis provided 34, which was subjected to the condensation conditions with 3 without isolation. Two benzyl groups were then removed with BCl_3, in the presence of excess pentamethylbenzene as a scavenger of benzyl cation. Finally, spirocyclopropanation was carried out according to Boger's conditions to furnish (+)-1, which was identical in all respects to the natural product.

  Symposium on the chemistry of natural products, Sep. 2006, Symposium on the Chemistry of Natural Products, symposium papers, (48) (48), 175 - 180, Japanese


• Total synthesis of (+)-yatakemycin

  Kentaro Okano, Hidetoshi Tokuyama, Tohru Fukuyama

  AMER CHEMICAL SOC, Jun. 2006, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 128(22) (22), 7136 - 7137, English

  [Refereed]

  Scientific journal


• Hydroesterification of vinylarenes catalyzed by palladium complexes of dialkylmonoaryl- and monoalkyldiarylphosphines

  Y Kawashima, K Okano, K Nozaki, T Hiyama

  Hydroesterification of vinylarenes using a mixture of PdCl2 and monodentate phosphorus ligands as a catalyst was studied. As ligands, menthyldiphenylphosphine (MDPP). neomenthyldiphenylphosphine (NMDPP), and dicyclohexyl(phenyl)phosphine (Cy2PPh) were effective to obtain branched esters with high regioselectivity under the moderate reaction conditions Without additives such as acids. Not only electronic effects but also steric effects of the cycloalkyl groups were revealed to be significant in order to achieve high catalytic activity. When (S)-2-dicyclopentylphosphino-2'-methoxy-1,1'-binaphthyl was used for the asymmetric hydroesterification of 2-methoxy-6-vinylnaphthalene, (S)-naproxen methyl ester was obtained with 53% ee.

  CHEMICAL SOC JAPAN, Feb. 2004, BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 77(2) (2), 347 - 355, English

  [Refereed]

  Scientific journal


• Synthesis of secondary arylamines through copper-mediated intermolecular aryl amination

  K Okano, H Tokuyama, T Fukuyama

  [GRAPHICS] A mild intermolecular copper-mediated amination of aryl iodides has been developed. The reaction takes place at room temperature or heating at 90 degreesC and tolerates halogens attached to the aromatic ring. Its synthetic applications include a synthetic protocol for unsymmetrical N,N'-dialkylated phenylenediamines and both a stepwise and a general synthetic method for N-aryl secondary amines via Ns-anilides (readily obtained by reaction of the Ns-amide).

  AMER CHEMICAL SOC, Dec. 2003, ORGANIC LETTERS, 5(26) (26), 4987 - 4990, English

  [Refereed]

  Scientific journal

• Trapping of Transient Organolithium Compounds

  Kengo Inoue, Kentaro Okano

  Organolithium chemistry has been widely utilized in organic synthesis as a reliable tool for introducing various functional groups. The intrinsic high reactivity of organolithiums allows rapid chemical transformation however, the transient organolithiums bearing an electrophilic moiety often cause the undesired reactions such as self-dimerization, isomerization, and decomposition, which prevent further synthetic application. In this minireview, we classify the reactions involving the short-lived organolithiums and focus on the recent progress in flow chemistry, which allows to trap the highly reactive organolithium species. In addition, this review includes other approaches using the related organometallic species that can be performed in a conventional batch reactor. To place the recent development of this field in perspective, the established strategies controlling the reactivities of the short-lived organolithiums provide a short-step, efficient, and protective group-free synthesis of functionalized organic molecules in medicinal, agrochemical, and material chemistry.

  Wiley-VCH Verlag, 01 Oct. 2020, Asian Journal of Organic Chemistry, 9(10) (10), 1548 - 1561, English

  Book review


• ラジカル転位環化反応を用いた(-)‐Histrionicotoxinの全合成

  佐藤学, 我妻弘基, 大学明広, 高須清誠, 岡野健太郎, 徳山英利

  02 Nov. 2015, 複素環化学討論会講演要旨集, 45th, 311 - 312, Japanese


• Total Synthesis of (-)-Haouamine B Pentaacetate and Structural Revision of Haouamine B

  Hidetoshi Tokuyama, Kentaro Okano, Kenji Sugimoto, Yuichi Momoi, Keiichiro Okuyama, Hiroki Toya

  GEORG THIEME VERLAG KG, Mar. 2015, SYNTHESIS-STUTTGART, 47(5) (5), A42 - A45, English

  Others


• (-)‐Penitrem Eの合成研究

  OTSU TAKANORI, YOSHII YU, HOSOKAWA NORIHIKO, TAKASU KIYOSEI, OKANO KENTARO, TOKUYAMA HIDETOSHI

  27 Oct. 2014, 有機合成シンポジウム講演要旨集, 106th, 52 - 53, Japanese


• ラジカル転位環化反応を用いるアザスピロ環の不斉構築を基盤としたHistrionicotoxinの合成研究

  OKANO KENTARO, WAGATSUMA HIROKI, SATO MANABU, DAIGAKU AKIHIRO, TAKASU KIYOSEI, TOKUYAMA HIDETOSHI

  22 Oct. 2014, 反応と合成の進歩シンポジウム講演要旨集, 40th, 100, Japanese


• ラジカル転位環化反応を用いたHistrionicotoxin類の合成研究

  AZUMA HIROKI, SATO MANABU, DAIGAKU AKIHIRO, TAKASU KIYOSEI, OKANO KENTARO, TOKUYAMA HIDETOSHI

  06 Jun. 2014, シンポジウム「モレキュラー・キラリティー」講演要旨集, 2014, (JA)103,(EN)102, Japanese


• 不安定な七員環をいかにつくるか？アセチルアラノチンの全合成

  TOKUYAMA Hidetoshi, OKANO Kentaro

  2014, 化学, 69(2) (2), 68 - 69, Japanese

  [Refereed][Invited]

  Introduction commerce magazine


• Copper-mediated aromatic amination reaction and its application to the total synthesis of natural products

  Kentaro Okano, Hidetoshi Tokuyama, Tohru Fukuyama

  ROYAL SOC CHEMISTRY, 2014, CHEMICAL COMMUNICATIONS, 50(89) (89), 13650 - 13663, English

  [Refereed][Invited]

  Introduction scientific journal


• Synthetic Studies on Natural Products with Aromatic Nitrogen Heterocycles Based on Development of the Methods for the Formation of Aryl Carbon-Nitrogen Bond

  Kentaro Okano

  Total syntheses of yatakemycin, PDE-II, dictyodendrins, and heptaphylline are described. This article focuses on the formation of aryl carbon-nitrogen bonds by two methods: first by an aromatic amination reaction using a combination of CuI and CsOAc, and then by a benzyne-mediated one-pot cyclization-functionalization sequence. The aryl amination reaction shows a high functional group compatibility and applicability for highly hindered substrates. The utility of this reaction has been fully demonstrated through a total synthesis of yatakemycin, which features the regioselective ring opening of (S)-epichlorohydrin with 2,6-dibromophenyllithium species and the efficient deprotection of benzyl groups of aryl benzyl ether with BCl3 in the presence of pentamethylbenzene. The copper-mediated aryl amination reaction was applied to a one-pot double aryl amination for facile access to the highly substituted pyrroloindole skeleton, which led to a concise total synthesis of PDE-II. A highly efficient total synthesis of dictyodendrins A-E was accomplished by the development of a novel benzyne-mediated one-pot indoline formation/cross-coupling sequence for the construction of a highly substituted key indoline intermediate. Peripheral substituents were introduced onto this intermediate in a modular fashion to complete the total synthesis of dictyodendrins A-E. The utility of the one-pot benzyne-mediated cyclization-functionalization reaction was demonstrated by the total synthesis of carbazole alkaloid, heptaphylline.

  PHARMACEUTICAL SOC JAPAN, Oct. 2013, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 133(10) (10), 1065 - 1078, Japanese

  [Refereed][Invited]

  Book review


• Total Syntheses of Mersicarpine

  Yusuke Iwama, Kentaro Okano, Hidetoshi Tokuyama

  This review focuses on synthetic studies on mersicarpine that has a characteristic skeleton including seven-membered cyclic imine fused with indoline and delta-lactam. After a brief discussion of structural features and proposed biogenesis of this compound, several synthetic efforts toward construction of mersicarpine core are described. Total syntheses of mersicarpine are described including Kerr's racemic synthesis utilizing a formation of seven-membered cyclic imine from alpha-hydroxyketone prepared by oxidation of indole, racemic syntheses of the Kerr's synthetic intermediate by Zard and Han, the first enantiocontrolled total synthesis by Fukuyama based on the construction of seven-membered alpha-hydroxyimine by autoxidation of azepinoindole, and the second enantiocontrolled synthesis by Tokuyama employing a DIBALH-mediated ring-expansion reaction of cyclic ketoxime fused with indole.

  SOC SYNTHETIC ORGANIC CHEM JPN, Sep. 2013, JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 71(9) (9), 926 - 934, Japanese

  [Refereed][Invited]

  Introduction scientific journal


• 不斉転写型ラジカル転位環化反応を利用した(-)‐HTXの合成研究

  AZUMA HIROKI, DAIGAKU AKIHIRO, TAKASU KIYOSEI, OKANO KENTARO, TOKUYAMA HIDETOSHI

  02 Jun. 2012, 万有生命科学振興国際交流財団仙台シンポジウム, 23rd, 62, Japanese


• 不斉転写型ラジカル転位環化反応を利用した(-)‐Histrionicotoxinの合成研究

  AZUMA HIROMOTO, DAIGAKU AKIHIRO, TAKASU KIYOSEI, OKANO KENTARO, TOKUYAMA HIDETOSHI

  30 May 2012, 有機合成シンポジウム講演要旨集, 101st, 113 - 116, Japanese


• ラジカル転位環化反応を利用した(-)‐Histrionicotoxinの合成研究

  AZUMA HIROKI, DAIGAKU AKIHIRO, OKANO KENTARO, TAKASU KIYOSEI, TOKUYAMA HIDETOSHI

  05 Mar. 2012, 日本薬学会年会要旨集, 132nd(2) (2), 111, Japanese


• Penitrem Eの合成研究

  YOSHII YU, OTSU TAKANORI, OKANO KENTARO, HOSOKAWA NORIHIKO, TAKASU KIYOSEI, TOKUYAMA HIDETOSHI

  05 Mar. 2012, 日本薬学会年会要旨集, 132nd(2) (2), 140, Japanese


• Petrosinの不斉全合成および抗HIV活性に関する構造活性相関研究

  SATO TAKAHITO, TOTANI HIROKI, OKANO KENTARO, TAKASU KIYOMASA, IHARA MASATAKA, TAKAHASHI JUN, TANAKA HARUO, TOKUYAMA HIDETOSHI

  05 Mar. 2012, 日本薬学会年会要旨集, 132nd(2) (2), 219, Japanese


• 23 Total Synthesis of (-)-Perhydrohistrionicotoxin using Radical Translocation-Cyclization Reaction(Oral Presentation)

  Azuma Hiroki, Daigaku Akihiro, Fujitani Manabu, Okano Kentaro, Takasu Kiyosei, Tokuyama Hidetoshi

  Histrionicotoxin (1) and perhydrohistrionicotoxin (2), are non-competitive blockers of nicotinic acetylcholine-acceptors. The important bioactivity and the characteristic azaspirocyclic skeleton have attracted considerable interests from the synthetic community. However, there are few effective methods for enantiocontrolled construction of the azaspirocyclic ring. Herein, we report a diastereoselective construction of the core six-membered spirolactam utilizing a radical translocation-cyclization strategy and application to a total synthesis of (-)-2. In our preliminary experiments, the radical reaction using enantiomerically pure lactam 6 resulted in significant decrease of the enantiomeric purity, which indicated inversion of the sp^3 radical center generated via 1,5-hydrogen radical shift was much faster than cyclization. Based on these results, we considered a stereoselective radical reaction with chiral-transfer from other stereocenter introduced on the side chain. With this idea in mind, we examined radical reaction with diastereomeric 16 or 19 having the same chiral side chain. As we expected, the reactions of both compounds gave the same 18 albeit in low yield probably due to the undesired radical translocation to the a-position of the silyloxy group. The low yielding problem was circumvented by conducting the reaction with ketal 22 with no hydrogen. Encouraged by this successful result, we then investigated the diastereoselective radical reaction of a substrate with a chiral ketal moiety derived from a C_2-symmetrical diol. Among a variety of diols tested, we found that 2,4-pentanediol was effective for achieving high enantiomeric excess. Based on the formation of the azaspirocyclic compound 31, we accomplished a total synthesis of (-)-perhydrohistrionicotoxin (2).

  Symposium on the Chemistry of Natural Products Steering Committee, 2012, Symposium on the Chemistry of Natural Products, symposium papers, 54(0) (0), 133 - 138, Japanese


• Petrosinの不斉全合成および抗HIV活性に関する構造活性相関研究

  SATO TAKAHITO, TOTANI HIROKI, OKANO KENTARO, TAKASU KIYOSEI, IHARA MASATAKA, TAKAHASHI JUN, TANAKA HARUO, TOKUYAMA HIDETOSHI

  2012, 日本薬学会東北支部大会講演要旨集, 51st, 32, Japanese


• (-)‐および(+)‐petrosinの全合成

  TOTANI HIROKI, OKANO KENTARO, TAKASU KIYOSEI, IHARA MASATAKA, TAKAHASHI JUN, TANAKA HARUO, TOKUYAMA HIDETOSHI

  05 Mar. 2011, 日本薬学会年会要旨集, 131st(2) (2), 143, Japanese


• Total syntheses of nitrogen-containing cyclic natural products based on aryl amination

  Kentaro Okano, Tohru Fukuyama, Hidetoshi Tokuyama

  This article focuses on the development of an aromatic amination reaction using CuI and CsOAc and its application to total syntheses of nitrogen-containing cyclic natural products. The reaction conditions present several unprecedented features that have not been observed in conventional palladium-catalyzed systems, including high functional group compatibility (e.g., N-alloc-and sp2-Br are retained) and applicability for highly hindered substrates. The utility of this reaction has been fully demonstrated through total syntheses of duocarmycins, yatakemycin, and PDE-II.

  Oct. 2010, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 68(10) (10), 1036 - 1046, Japanese


• Total Syntheses of Nitrogen-Containing Cyclic Natural Products Based on Aryl Amination

  Kentaro Okano, Tohru Fukuyama, Hidetoshi Tokuyama

  This article focuses on the development of an aromatic amination reaction using CuI and CsOAc and its application to total syntheses of nitrogen-containing cyclic natural products. The reaction conditions present several unprecedented features that have not been observed in conventional palladium-catalyzed systems, including high functional group compatibility (e.g., N-alloc-and sp(2)-Br are retained) and applicability for highly hindered substrates. The utility of this reaction has been fully demonstrated through total syntheses of duocarmycins, yatakemycin, and PDE-II.

  SOC SYNTHETIC ORGANIC CHEM JPN, Oct. 2010, JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 68(10) (10), 1036 - 1046, Japanese

  [Refereed]

  Introduction scientific journal


• (-)および(+)‐Petrosinの全合成

  TOYA HIROKI, OKANO KENTARO, TAKAHASHI ATSUSHI, TANAKA HARUO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  14 Sep. 2010, 複素環化学討論会講演要旨集, 40th, 73 - 74, Japanese


• (-)および(+)‐Petrosinの全合成

  OKANO KENTARO, TOYA HIROKI, TAKAHASHI ATSUSHI, TANAKA HARUO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  02 Sep. 2010, 有機合成化学セミナー講演予稿集, 27th, 112, Japanese


• (-)および(+)‐Petrosinの全合成

  TOYA HIROKI, OKANO KENTARO, TAKAHASHI ATSUSHI, TANAKA HARUO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  Petrosin (1), isolated as a racemate from the marine sponge Petrosia seriata by Braekman in 1982, by and Kitagawa and Kobayashi in 1989, independently, is known to possess anti-HIV activity by inhibitions of reverse transcriptase and giant cell formation. The first racemic total synthesis of 1 has been reported by Heathcock and co-workers in 1994, who also confirmed that all stereocenters of the quinolizidine rings easily epimerized via retro-Mannich and Mannich reaction. Since the anti-HIV activity of each enantiomer has not yet been investigated, we initiated synthetic studies on petrosin in optically active form to examine the bioactivity between each enantiomer. First, optically active hemiaminal 6, prepared via desymmetrization of prochiral 1,3-diol, was treated with ketene silyl acetal 7 in the presence of catalytic TBSOTf to provide the desired product 5. Vinyl iodide 19 was prepared from 5 via modification of the side chain. Union of the fully elaborated monomer segments 5 and 19 was conducted by Suzuki-Miyaura coupling to afford dimer 20 in 89% yield. Stereoselective constuction of the quinolizidine rings was then conducted by aza-Michael reaction. The crucial formation of the 16-membered ring was effectively executed by ring-closing metathesis with the 2^ generation Grubbs catalyst. Based on the Grubb's modification, we added p-quinone to avoid isomerization of C-C double bond. Finally, the double bond was reduced under hydrogenation conditions to give (-)-petrosin (1). The optical purity of the synthetic petrosin (>99% ee) was confirmed by Mosher's method for a diol derived from 1 by reduction of two carbonyl groups, indicating that epimerization of optically active petrosin did not proceed. We also synthesized (+)-1 in the same manner from the other enantiomer of hemiaminal 6. We then evaluated inhibitoty activity against syncytium formation. While a significant difference was not observed between each enantiomer, the partial structure 13 exhibited no inhibitory activity against giant cell formation. The results indicated that the dimeric structure would be essential for the bioactivity.

  Symposium on the chemistry of natural products, 01 Sep. 2010, 天然有機化合物討論会講演要旨集, 52nd(52) (52), 229 - 234, Japanese


• (±)‐Lepadiformine Aの全合成

  FUJITANI MANABU, TSUCHIYA MASAMI, OKANO KENTARO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  05 Mar. 2010, 日本薬学会年会要旨集, 130th(2) (2), 141, Japanese


• アリル位C-H酸化が切り開くマクロリド合成の新展開

  岡野 健太郎

  2010, ファルマシア, 46(6) (6), 548 - 549, Japanese

  [Refereed]

  Introduction scientific journal


• 抗HIV活性を示す(-)‐Petrosinの不斉全合成

  OKANO KENTARO, TOYA HIROKI, TAKAHASHI ATSUSHI, TANAKA HARUO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  10 Nov. 2009, メディシナルケミストリーシンポジウム講演要旨集, 28th, 170 - 171, Japanese


• Synthetic Studies on(-)-Histrionicotoxin by Radical Translocation-Cyclization

  DAIGAKU AKIHIRO, OKANO KENTARO, TAKASU KIYOSEI, TOKUYAMA HIDETOSHI

  25 Sep. 2009, 複素環化学討論会講演要旨集, 39th, 37 - 38, Japanese


• Lepadiformine類の合成研究

  FUJITANI MANABU, TSUCHIYA MASAMI, OKANO KENTARO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  19 Sep. 2009, 化学系学協会東北大会プログラムおよび講演予稿集, 2009, 73, Japanese


• 9環性インドールアルカロイドPenitrem Eの合成研究

  OTSU TAKANORI, HOSOKAWA NORIHIKO, TAKASU KIYOSEI, OKANO KENTARO, TOKUYAMA HIDETOSHI

  11 Sep. 2009, 有機合成化学セミナー講演予稿集, 26th, 89, Japanese


• 9環性インドールアルカロイドPenitrem Eの合成研究

  OTSU TAKANORI, HOSOKAWA NORIHIKO, OKANO KENTARO, TAKASU KIYOSEI, TOKUYAMA HIDETOSHI

  05 Mar. 2009, 日本薬学会年会要旨集, 129th(2) (2), 110, Japanese


• Petrosinの全合成

  TOTANI HIROKI, OKANO KENTARO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  2009, 有機合成シンポジウム講演要旨集, 95th, 145 - 148, Japanese


• Synthetic studies on haouamines with highly strained paracyclophane skeleton

  Kentaro Okano

  Recent development of synthetic studies on novel marine alkaloids, haouamine A and B, is described. Haouamines have attracted considerable attention of synthetic chemists because of their unique structure and selective activity against human colon carcinoma cell line HT-29, however, only two groups have so far reported successful formation of their highly strained 3-aza-[7]-paracyclophane core. This review focuses on synthetic efforts to construct the core skeleton of haouamines reported by Baran and Wipf.

  SOC SYNTHETIC ORGANIC CHEM JPN, Apr. 2008, JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 66(4) (4), 387 - 388, Japanese

  [Refereed]

  Book review


• 抗HIV作用を持つPetrosinの合成研究

  TOYA HIROKI, OKANO KENTARO, TAKASU KIYOMASA, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  05 Mar. 2008, 日本薬学会年会要旨集, 128th(2) (2), 15, Japanese


• (-)‐ヒストリオニコトキシンの合成研究

  DAIGAKU AKIHIRO, OKANO KENTARO, TAKASU KIYOMASA, TOKUYAMA HIDETOSHI

  05 Mar. 2008, 日本薬学会年会要旨集, 128th(2) (2), 137, Japanese


• Lepadiformine類の合成研究

  FUJITANI MANABU, TSUCHIYA MASAMI, OKANO KENTARO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  2008, 日本薬学会東北支部大会講演要旨集, 47th, 20, Japanese


• (-)‐Histrionicotoxinの合成研究

  DAIGAKU AKIHIRO, OKANO KENTARO, TAKASU KIYOSEI, TOKUYAMA HIDETOSHI

  2008, 日本薬学会東北支部大会講演要旨集, 47th, 20, Japanese


• 抗HIV作用を持つPetrosinの合成研究

  TOTANI HIROKI, OKANO KENTARO, TAKASU KIYOSEI, IHARA MASATAKA, TOKUYAMA HIDETOSHI

  2007, 日本薬学会東北支部大会講演要旨集, 46th, 19, Japanese

• 天然物合成で活躍した反応 実験のコツとポイント

  OKANO KENTARO

  Joint work, 化学同人, 2011, Japanese

  Scholarly book


• 天然物の全合成 2000〜2008（日本）

  OKANO KENTARO

  Joint work, 化学同人, 2009, Japanese

  Scholarly book


• 演習で学ぶ有機反応機構

  OKANO KENTARO

  Joint work, 化学同人, 2005, Japanese

  Scholarly book

• 不安定カルボアニオンの制御を基盤とするヘテロ芳香族化合物の官能基化（招待講演）

  OKANO Kentaro

  日本薬学会北陸支部 特別講演会, Dec. 2018, Japanese, Domestic conference

  [Invited]

  Invited oral presentation


• ハロゲンダンスの制御を基盤とするヘテロ芳香族化合物の官能基化

  OKANO Kentaro

  第4回近畿薬学シンポジウム：化学系の若い力, Sep. 2018, Japanese, Domestic conference

  [Invited]

  Invited oral presentation


• 機能性チオフェンの構造設計と精密重合

  MORI ATSUNORI, FUJITA KEISUKE, OGURA TADAYUKI, KUBOTA CHIHIRO, OKANO KENTARO, FUNAHASHI MASAHIRO

  第６７回高分子討論会, Sep. 2018, Japanese, 高分子学会, 北海道大学, Domestic conference

  [Invited]

  Invited oral presentation


• Synthesis of water-soluble regioregular polythiophenes

  MORI ATSUNORI, FUJITA KEISUKE, OGURA TADAYUKI, KUBOTA CHIHIRO, OKANO KENTARO, FUNAHASHI MASAHIRO

  The 22th International Symposium on Advanced Display Materials and Devices (ADMD 2018), Jul. 2018, English, Ulsan National Institute of Science and Gechnology (UNIST), Jeju, Korea, International conference

  [Invited]

  Invited oral presentation


• ブロモチオフェンの金ナノ粒子上におけるハロゲンダンス

  AOKI Masato, MIYAGAQA Naoki, OKANO KENTARO, MORI Astunori

  日本化学会第９８春季年会, Mar. 2018, Japanese, 日本化学会, 日本大学船橋キャンパス, Domestic conference

  Oral presentation


• Recent Development of Halogen Dance

  OKANO KENTARO

  International Congress on Pure & Applied Chemistry (ICPAC) 2018, Mar. 2018, English, Siem Reap, Cambodia, International conference

  [Invited]

  Invited oral presentation


• ハロゲンダンスを基盤としたヘテロ芳香族化合物の集積型官能基化

  OKANO KENTARO

  新学術領域研究「反応集積化が導く中分子戦略：高次生物機能分子の創製平成２９年度第5回成果報告会, Jan. 2018, Japanese, 大阪大学豊中キャンパス, Domestic conference

  Oral presentation


• Deprotonation of Dibromothiophenes Controlled by Flash Chemistry

  OKANO KENTARO, RIKAKO TADA, YOSHIKI YAMANE, AIICHIRO NAGAKI, JUNICHI YOSHIDA, MORI ATSUNORI

  The First International Conference on Automated Flow and Microreactor Synthesis（ICAMS-1）, Jan. 2018, English, 大阪, International conference

  Poster presentation


• Synthesis of Thienoindoles by Halogen Dance and Ligand-Controlled One-Pot Sequential Coupling Reactions

  YUKI HAYASHI, OKANO KENTARO, MORI ATSUNORI

  The 11th International Symposium on Integrated Synthesis, Nov. 2017, English, 淡路島, International conference

  Poster presentation


• Synthesis of Furan-Dimer Based Biopolyester

  NAOKI MIYAGAWA, TADAYUKI OGURA, OKANO KENTARO, TAKUYA MATSUMOTO, TAKASHI NISHINO, MORI ATSUNORI

  The 11th International Symposium on Integrated Synthesis, Nov. 2017, English, 淡路島, International conference

  Poster presentation


• Regiocontrolled Halogen Dance of α-Bromothiophenes and α-Bromofurans

  DAICHI MARI, NAOKI MIYAGAWA, OKANO KENTARO, MORI ATSUNORI

  The 11th International Symposium on Integrated Synthesis, Nov. 2017, English, 淡路島, International conference

  Poster presentation


• Deprotonation of Dibromothiophenes Controlled by Flash Chemistry

  RIKAKO TADA, YOSHIKI YAMANE, AIICHIRO NAGAKI, JUNICHI YOSHIDA, OKANO KENTARO, MORI ATSUNORI

  The 11th International Symposium on Integrated Synthesis, Nov. 2017, English, 淡路島, International conference

  Poster presentation


• ハロゲンダンスを用いる多置換ヘテロ芳香族化合物の合成

  OKANO KENTARO, MORI ATSUNORI

  第３５回メディシナルケミストリーシンポジウム, Oct. 2017, Japanese, 名古屋大学, Domestic conference

  Poster presentation


• 新規合成方法論の開発を基盤とする含窒素高次縮環天然物の全合成（奨励賞受賞講演）

  OKANO KENTARO

  第３４回有機合成化学セミナー, Sep. 2017, Japanese, 金沢市文化ホール, Domestic conference

  [Invited]

  Invited oral presentation


• 高歪み中間体の効率的発生方法の開発

  HIOKI YUTO, OKANO KENTARO, MORI ATSUNORI

  GSCシンポジウム, Jul. 2017, Japanese, 東京国際フォーラム・ホール, Domestic conference

  Poster presentation


• ハロゲンダンスを基盤としたヘテロ芳香族化合物の集積型官能基化

  OKANO KENTARO

  新学術領域研究「反応集積化が導く中分子戦略：高次生物機能分子の創製平成２９年度第４回成果報告会, Jul. 2017, Japanese, 京都大学桂キャンパス船井講堂, Domestic conference

  Poster presentation


• マグネシウムビスアミドを用いるシクロアルキンの脱プロトン的発生法の開発

  HIOKI YUTO, OKANO KENTARO, MORI ATSUNORI

  第111回有機合成シンポジウム, Jun. 2017, Japanese, 有機合成化学協会, 岡山大学津島キャンパス, Domestic conference

  Oral presentation


• Control of transient anion species for synthesis of multiply substituted heteroaromatic compounds

  OKANO Kentaro

  MPI-KobeU-RIKEN Joint Symposium, Feb. 2017, English, International conference

  [Invited]

  Invited oral presentation


• フルフラールを原料とする共役系ポリマーの合成

  MURASE YUKI, ASHIDA KANA, MIYAGAWA NAOKI, OKANO KENTARO, MORI ATSUNORI

  高分子研究会（神戸）, Jul. 2016, Japanese, 高分子学会関西支部, 神戸県民会館, Domestic conference

  Poster presentation


• Kinetic Resolution of Heterobiaryl Derivatives with Winding-vine-shaped Molecular Asymmetry

  MARUHASHI KAZUKI, YOICHI OKAYAMA, TOYOMORI YUKA, OKANO KENTARO, MORI ATSUNORI

  Molecular Chirality Asia 2016 – Chiral Science and Technology: From Asia to the World –, Apr. 2016, English, Knowledge Capital Congress Convention Center, International conference

  Poster presentation


• 炭素－塩素結合をもつチオフェン誘導体のC-H結合におけるカップリング反応によるチオフェン－チオフェン結合の生成

  FUJITA KEISUKE, NAKAGAWA NAOKI, SUNAHARA KAZUHIRO, YAMANE YOSHIKI, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• マグネシウムビスアミドを用いるブロモチオフェン類のハロゲンダンス

  YAMANE YOSHIKI, SUNAHARA KAZUHIRO, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• マグネシウムビスアミドを用いるエノールトリフラートの脱プロトン的シクロアルキン発生法の開発

  HIOKI YUTO, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• ハロゲンダンスを利用したポリアリールチオフェン類の効率的合成法の開発

  SUNAHARA KAZUHIRO, YAMANE YOSHIKI, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• つるまき状分子不斉を有するビチオフェン誘導体の速度論的光学分割

  ASHIDA SHIOMI, OKAYAMA YOICHI, TOYOMORI YUKA, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• つるまき状分子不斉を有するビスイミダゾール誘導体の速度論的光学分割

  MARUHASHI KAZUKI, INOUE RYO, JIN GUANHONG, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• チオフェン誘導体のC-Hカップリング重合における配位子効果の検討

  OGURA TADAYUKI, NAKAGAWA NAOKI, FUJIO MAKOTO, HASHIMOTO TAKAYOSHI, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• チオフェン誘導体のC-Hカップリング重合におけるモノマー構造多様性の検討

  NAKAGAWA NAOKI, OGURA TADAYUKI, FUJITA KEISUKE, SUMINO YUGO, FUKUI YUTA, OKANO KENTARO, MORI ATSUNORI

  日本化学会第96春季年会, Mar. 2016, Japanese, 日本化学会, 同志社大学, Domestic conference

  Oral presentation


• カルボアニオンの反応性制御を基盤とする多置換ヘテロ芳香族化合物の合成

  OKANO Kentaro

  ヘテロ原子部会平成２７年度第３回懇話会, Feb. 2016, Japanese, Domestic conference

  [Invited]

  Invited oral presentation


• 特異な骨格を有するアルカロイド類の合成研究

  OKANO Kentaro

  分子イメージングセミナー RIKEN Molecular Imaging Seminar, Sep. 2015, Japanese, Domestic conference

  [Invited]

  Invited oral presentation


• 特異な骨格を有するアルカロイド類の合成研究

  OKANO Kentaro

  岡山大学異分野融合研究育成支援事業「有機合成を基盤とした生体機能制御分子の創製」第2回講演会, Jul. 2015, Japanese, Domestic conference

  [Invited]

  Invited oral presentation


• Total Synthesis of (+)-Yatakemycin

  ICOB-5&ISCNP-25 IUPAC, International Conference on Biodiversity and Natural Product, 2006

  Poster presentation


• (+)-Yatakemycinの全合成

  第48回天然有機化合物討論会, 2006


• Total Synthesis of (+)-Yatakemycin

  ICOB-5&ISCNP-25 IUPAC, International Conference on Biodiversity and Natural Product, 2006

  Poster presentation


• (+)-Yatakemycinの全合成

  第48回天然有機化合物討論会, 2006


• Synthetic Studies on (+)-Yatakemycin

  2005環太平洋国際化学会議, 2005

  Poster presentation


• (+)-ヤタケマイシンの全合成研究

  第87回有機合成シンポジウム, 2005


• (+)-ヤタケマイシンの全合成研究

  第87回有機合成シンポジウム, 2005


• Synthetic Studies on (+)-Yatakemycin

  2005環太平洋国際化学会議, 2005

  Poster presentation

• 国際複素環化学会


• The Society of Synthetic Organic Chemistry, Japan


• The Chemical Society of Japan


• The Pharmaceutical Society of Japan


• 近畿化学協会


• 日本薬学会


• 日本化学会


• 有機合成化学協会

• Development of Direct Functionalization of Heteroaromatic Compounds Based on Trapping of the Short-lived Carbanions

  岡野 健太郎

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, Apr. 2019 - Mar. 2023, Principal investigator

  2020年度は、前年度に達成したルキアノールやニンガリン、ラメラリン類などのピロール天然物の全合成において、鍵反応として用いたブロモピロールのハロゲンダンスの一般性を検証した。特に、ピロール窒素上の置換基として、スルホニル基を用いると円滑にハロゲンダンスが進行することがわかった。また、予備的検討として、精密in situトランスメタル化にも成功し、ハロゲンダンスに含まれる二種類の有機リチウムをそれぞれ対応する有機亜鉛反応剤として利用することができた。この知見に基づき、上記ピロール天然物の合成において、課題として残されていた二つのβ位ブロモ基の位置選択的な変換反応についても、一定の解決法を提示することができた。以上の知見により、多置換ピロールの合成法を確立した。 ハロゲンダンスにおいて、反応系中で発生する短寿命炭素アニオンをin situトランスメタル化するためのハロゲン化亜鉛ジアミン錯体を10種類以上合成し、幅広いブロモアレーン類について、その有用性を検証した。その結果、チエニルリチウムと比較すると、不安定なフリルリチウムやピロリルリチウムなどの短寿命炭素アニオンにも本方法を適用できた。さらに、これまでバッチ法では捕捉できなかったハロゲンダンスの前後の不安定炭素アニオンの合成的な利用についても検討を進めたところ、アゾール類についても、本手法が有効であることがわかった。 マイクロフローリアクターを活用する、短寿命炭素アニオンの選択的な捕捉については、ジブロモチオフェンのブロモ基の置換位置によって、対応する炭素アニオンが捕捉可能かどうかを明らかにした。すなわち、2,3-ジブロモチオフェン由来の5位リチオ化体はさまざまな求電子剤で捕捉できたが、2,5-ジブロモチオフェン由来の3位リチオ化体については、条件検討にもかかわらず、ハロゲンダンスが優先することがわかった。

  Competitive research funding


• 高ひずみ短寿命中間体の実用的発生法の開発

  岡野 健太郎

  公益財団法人 ハーモニック伊藤財団, 2019年度助成金, Apr. 2019 - Mar. 2021, Principal investigator

  Competitive research funding


• 高ひずみ短寿命炭化水素の実用的発生法の開発と機能性高分子の合成

  岡野 健太郎

  公益財団法人 総合工学振興財団, 令和元年度研究奨励, Apr. 2019 - Mar. 2020, Principal investigator

  Competitive research funding


• 精密in situトランスメタル化を鍵とするハロゲンダンスの制御

  岡野 健太郎

  公益財団法人 京都技術科学センター, 2019年度研究開発助成, Apr. 2019 - Mar. 2020, Principal investigator

  Competitive research funding


• 高ひずみ炭化水素前駆体の実用的合成と機能性分子の創製

  岡野 健太郎

  公益財団法人 東燃ゼネラル石油研究奨励・奨学財団, 第38回（平成30年度）東燃ゼネラル石油研究奨励助成, Mar. 2019 - Mar. 2020, Principal investigator

  Competitive research funding


• Integrated Synthesis of Heteroaromatic Compounds Based on Control of Halogen Dance

  岡野 健太郎

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Kobe University, Apr. 2018 - Mar. 2020, Principal investigator

  2019年度は、ブロモ基が分子内で動きながらワンポットで二つの結合を形成するハロゲンダンスを鍵として、ルキアノールAおよびB、ニンガリンB、ラメラリンSおよびZの全合成を達成した。二つのブロモ基を足がかりに、上部芳香環を位置選択的カップリングにより導入する集積型合成法が、関連する化合物群の合成に広く応用できることを示した。また、ハロゲンダンスの後、有機亜鉛反応剤へのトランスメタル化を経て根岸カップリングする、ラメラリン類の第二世代合成も達成した。 バッチ系にてハロゲンダンスが進行する、その他のヘテロ芳香族化合物を基質としてマイクロフロー反応を実施し、いくつかの基質においてハロゲンダンス前後の短寿命アリールリチウムを捕捉する条件を見出した。その過程で、攪拌効率が、選択性に大きく影響することも確認した。特に、バッチ型反応装置では開環反応を経て分解するチアゾールについて、マイクロフロー反応によりハロゲンダンス前の短寿命アリールリチウムを捕捉することにも成功し、フローマイクロリアクターの合成的有用性を示すことができた。 ハロゲンダンスにおいて、反応系中で発生する短寿命炭素アニオンの捕捉を検討する中で見出した、金属ジアミン錯体によるin situトランスメタル化を利用すると、フローマイクロリアクターでは選択的な捕捉が困難であった、2,5-ジブロモチオフェン由来の炭素アニオンを捕捉できた。さらに、新規金属ジアミン錯体を合成し、その他の従来合成的に利用できなかったアニオンの捕捉も実現した。

  Competitive research funding


• Development of Halogen Dance and Cycloalkyne Formation Utilizing Magnesium Amides

  Okano Kentaro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, Apr. 2016 - Mar. 2019, Principal investigator

  Effects of amide bases on halogen dance were investigated. Compared to the conventional lithium amides, the magnesium bisamide can control halogen dance of 2,3-dibromothiophene to provide both products that are derived from the two carbanion species. In addition, magnesium amide facilitated the formation of cycloalkanes from the enol triflates, which were prepared from the corresponding ketones in one step.

  Competitive research funding


• カルボアニオンの反応性制御を基盤としたワンポット連続反応の開発

  岡野 健太郎

  公益財団法人 川西記念新明和教育財団, 平成28年度 研究助成金, Apr. 2016 - Mar. 2018, Principal investigator

  Competitive research funding


• ハロゲンダンスを基盤としたヘテロ芳香族化合物の集積型官能基化

  岡野 健太郎

  日本学術振興会, 科学研究費補助金／新学術領域研究, 新学術領域研究(研究領域提案型), 神戸大学, Apr. 2016 - Mar. 2018, Principal investigator

  平成29年度は、バッチ系のハロゲンダンスにおいて、マグネシウムビスアミドMg(TMP)2・2LiClが室温下、円滑にハロゲンダンスを進行させることも確認した。従来用いられていた、LiTMPなどのリチウムアミドとは異なり、反応条件を適切に選択することで、ハロゲンダンスを停止させることも可能であった。これにより、置換様式の異なる多置換チオフェン類の合成が可能になった。また、マイクロフロー反応装置を用いることにより、リチウムアミドを用いるバッチ系では不可能であった変換にも成功した。また、非対称なブロモチオフェンやブロモフランのハロゲンダンスに、置換基がおよぼす影響を検討した。その結果、エステルやアミドが配向基として作用し、従来とは異なる1,3型の転位様式でハロゲンダンスが進行することを確認した。さらに、オキサゾリンを配向基として利用することで、これまでに報告例がないブロモピロールにおいてもハロゲンダンスが円滑に進行することを明らかにした。そこで、ハロゲンダンスの長所である、官能基導入の足がかりとなるハロゲン原子（ブロモ基）が転位しながら、求電子剤と反応する合成的有用性を示すため、多置換ピロールアルカロイド類の網羅的合成経路の確立を目標として、合成研究に取り組んだ。ハロゲンダンスを経て5位に移動したリチウム種を亜鉛にトランスメタル化し、パラジウム触媒による根岸カップリングにより三環性重要中間体を得た。

  Competitive research funding


• Development of mild oxidation reaction and its application to total synthesis of highly oxygenated natural products

  Okano Kentaro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Apr. 2013 - Mar. 2016, Principal investigator

  In this study we accomplished a total synthesis of MPC1001B, antiproliferative activity against DU145 human prostate cancer cell line, based on inversion of the two stereogenic centers that were generated in the key TBAF-mediated formation of the macrolactone. Preliminary experiments on introduction of the hydroxyl group on the dihydrooxepine skeleton for the late-stage oxidation were performed using a model substrate with selenium dioxide to establish mild oxidation conditions. We also investigated construction of the partial skeleton of aconitine through formation of enone from in five steps including Birch reduction. Conversion to the corresponding silyl enol ether followed by Diels-Alder reaction provided the desired tetracyclic compound, which was converted to the secondary alcohol. The mesylate was treated with silica gel to provide the allylic alcohol as a single isomer via Wagner-Meerwein rearrangement. Synthetic studies on acochlearine was also performed.

  Competitive research funding


• 植物由来アコニチンアルカロイド類の合成研究

  岡野 健太郎

  公益財団法人 松籟科学技術振興財団, 研究助成金, Apr. 2014 - Mar. 2015, Principal investigator

  Competitive research funding


• C-H活性化を鍵とする直接的ヘテロ原子導入法の開発

  岡野 健太郎

  日本学術振興会, 科学研究費補助金／新学術領域研究, 新学術領域研究(研究領域提案型), 東北大学, Apr. 2013 - Mar. 2015, Principal investigator

  平成26年度は、すでに全合成を達成したMPC1001Bの合成経路および反応条件の最適化を行うとともに、MPC1001BからMPC1001への変換について、既知のC-H酸化反応を含めて検討を行った。すなわち、MPC1001 に含まれるジヒドロオキセピン上のヒドロキシ基の導入について、合成終盤におけるアリル位酸化を検討した。その結果、二酸化セレンを用いた場合に、ジスルフィド結合がほぼ保持され、最終段階における酸化剤として有用であることがわかった。 タラチサミンおよびアコニチンの有する左部含窒素構造の構築を検討した。従来、多段階を必要としていた含窒素環状構造の構築について、短工程化を目的として各変換について検討した。その結果、ラジカル的連続反応を見出し、酸化的炭素炭素結合の形成に成功した。本反応を見出したことで、今後、これらアルカロイド類の右部の合成研究が円滑に行われると考えている。 また、複雑な縮環インドール骨格を有するアルカロイド、ペニトレム類の合成研究にも取り組んだ結果、パラジウム触媒を用いたC-H活性化（Catellani反応）を用いて、インドール4,5位に6員環炭素骨格を一挙に導入することに成功した。本変換により、その後の合成研究に必要な化合物を十分に供給することができた。最終的に、(2+2)環化付加反応を経て、ペニトレム類に共通するシクロブタン環を構築し、ペニトレムEの左側部分構造の合成に成功した。

  Competitive research funding


• 有用な生物活性を有するジチオジケトピペラジン天然物の合成研究

  岡野 健太郎

  公益財団法人 薬学研究奨励財団, 研究助成金グループＡ, Apr. 2013 - Mar. 2014, Principal investigator

  Competitive research funding


• 動的速度論的分割を鍵とするアザスピロ環の不斉構築

  岡野 健太郎

  公益財団法人 アステラス病態代謝研究会, 研究助成金, Apr. 2012 - Mar. 2013, Principal investigator

  Competitive research funding


• 多様な誘導体合成を指向した新規ジチオジケトピペラジン天然物の網羅的全合成

  岡野 健太郎

  公益財団法人 東京生化学研究会, 研究奨励金（Ⅰ）, Apr. 2012 - Mar. 2013, Principal investigator

  Competitive research funding


• マグネシウムビスアミドを用いる新規ベンザイン発生法の開発と生理活性天然物の全合成

  岡野 健太郎

  科学研究費補助金／若手研究（B）, Apr. 2011 - Mar. 2013, Principal investigator

  Competitive research funding


• Development of Benzyne Generation using Magnesium Bisamide andIts Application to Total Synthesis of Bioactive Natural Products

  OKANO Kentaro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Tohoku University, 2011 - 2012

  A synthetic method for the construction of multi-substituted nitrogen heterocycles such as indolines and carbazoles was established based on the development of mild generation of benzyne species using magnesium bisamide. The utility of this method was demonstrated by the total synthesis of heptaphylline and batzelline family as well as by its broad scope of substrates and electrophiles used in the reaction.


• 不斉転写型ラジカル反応を鍵とするHTXの合成研究

  岡野 健太郎

  公益信託 三菱化学研究奨励基金, 平成22年度研究助成金, Apr. 2010 - Mar. 2011, Principal investigator

  Competitive research funding


• ベンザインを経由するワンポット連続的環化ー官能基化に基づく多置換複素環骨格構築法の開発と生理活性天然物の革新的全合成

  岡野 健太郎

  公益財団法人 アステラス病態代謝研究会, 研究助成金, Apr. 2010 - Mar. 2011, Principal investigator

  Competitive research funding


• ベンザインを基軸とする多置換複素環化合物の新規合成法の開発と天然物合成への展開

  岡野 健太郎

  科学研究費補助金／若手研究（B）, Apr. 2009 - Mar. 2011, Principal investigator

  Competitive research funding


• Development of Synthetic Methodology for Multi-substituted Heterocycles via Benzyne Intermediate and Its Application for Natural Product Synthesis

  OKANO Kentaro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Tohoku University, 2009 - 2010

  Synthetic methodology for multi-substituted heterocycles was developed utilizing the high reactivity of benzyne intermediate. Magnesium bisamide was proved to be the best base for the benzyne generation and nucleophilic addition to construct heterocyclic skeletons. The resulting anion species reacted with a variety of electrophiles to give functionalized heteroaromatic compounds. The tricyclic skeleton of isobatzelline and discorhabdins was constructed using the reaction conditions.


• 第41回アメリカ有機化学シンポジウム

  岡野 健太郎

  財団法人 薬学研究奨励財団, 研究者の海外派遣に対する補助, Jun. 2009 - Jun. 2009, Principal investigator

  Competitive research funding


• テロメラーゼ阻害活性を有するディクティオデンドリン類の合成研究

  岡野 健太郎

  科学研究費補助金／スタートアップ, May 2007 - Mar. 2009, Principal investigator

  Competitive research funding


• Synthetic Studies on Telomerase Inhibitor, Dictyodendrins

  OKANO Kentaro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (Start-up), Grant-in-Aid for Young Scientists (Start-up), Tohoku University, 2007 - 2008

  本研究では、海綿から単離・構造決定されたテロメラーゼ阻害活性天然物ディクティオデンドリン類の合成研究を行った。その結果、ベンザインの高い反応性を利用する多置換インドリンの新規合成法を開発し、ディクティオデンドリンBの効率的全合成に成功した。さらに、ディクティオデンドリンAの世界初の全合成も達成した。本合成経路は合成終盤にさまざまな置換基を収束的に導入できることから、ディクティオデンドリン類の誘導体合成に応用可能である。


• ヤタケマイシンをはじめとする複雑な含窒素環状化合物の合成研究

  岡野 健太郎

  日本学術振興会, 科学研究費補助金／特別研究員奨励費, 特別研究員奨励費, Apr. 2006 - Apr. 2007, Principal investigator

  申請者は当研究室で開発された芳香族アミノ化反応を鍵反応として本化合物の合成研究を行うことで、これまで困難であった複雑な構造を有する含窒素環状化合物に対する一般性の高い新規合成法を確立できると考えている。前年度の研究成果として、強力なDNAアルキル化能を持つグラムスケールにてヤタケマイシンの全合成を達成している。本年度は、ヤタケマイシンの合成研究で得られた知見をもとに、海産性の天然物として初めてテロメラーゼ阻害活性(IC_<100>=50μM)を示すディクティオデンドリン類の合成研究を行った。本化合物群は二つの窒素原子を含む高度に置換された芳香環を有しており、これらが非常に電子豊富であることから、古典的な手法では合成がきわめて困難である。まずはディクティオデンドリン類全てに共通する4環性コア骨格の構築を当面の目標とした。100グラムスケールにて容易に調製可能なトリハロベンゼンから3工程で得られるスルホンアミドに対し、芳香族アミノ化反応が片方のプロモ基を完全に保持したまま、ほぼ定量的に進行することを見いだした。ここから、残されたブロモ基を足がかりとして種々のクロスカップリング反応を検討した結果、インドリン骨格を含む基質の場合は全く反応が進行しなかったが、インドール骨格へ酸化された基質を用いると望みのビアリール体を合成できた。また、続くアジドの熱分解も最適化は行っていないものの中程度の収率で4環性コア骨格を構築することに成功した。今後は残されたパラアニシル基の導入を経て全合成が達成できるものと考えている。

  Competitive research funding

• 脱水溶媒の調製方法

  村上 吉明, 坪内 源, 森 敦紀, 岡野 健太郎

  特願2019-034680, 27 Feb. 2019, 株式会社神鋼環境ソリューション, 国立大学法人神戸大学, 特開2020-138922, 03 Sep. 2020

  Patent right

  IRI


• 細胞内送達ベヒクル

  辻 俊一, 井門 久美子, 山田 小百合, 内山 聖一, 河本 恭子, 徳山 英利, 岡野 健太郎

  特願2020-027873, 21 Feb. 2020, キリンホールディングス株式会社, 国立大学法人 東京大学, 国立大学法人東北大学, 特開2020-097622, 25 Jun. 2020, 特許第6666673号, 26 Feb. 2020

  Patent right

  IRI


• フランオリゴマーポリエステルおよびその前駆体

  森 敦紀, 岡野 健太郎, 宮川 直樹, 松本 拓也

  特願2017-045892, 10 Mar. 2017, 国立大学法人神戸大学, 特開2018-150415, 27 Sep. 2018

  Patent right

  IRI