Innovation of the Asymmetric Reactions by Means of Chiral Bronsted Acid

• Project/Area Number: 23350046
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: Gakushuin University
• Principal Investigator: AKIYAMA TAKAHIKO 学習院大学, 理学部, 教授 (60202553)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2011: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 有機分子触媒 / キラルブレンステッド酸 / 不斉合成 / 不斉還元 / 触媒 / リン酸 / ブレンステッド酸 / マンニッヒ型反応 / 水素移動反応 / Mannich型反応 / ベンゾチアゾリン / Robinson環化反応 / 重水素還元

Research Abstract

Development of an efficient method for the preparation of the desired compounds is an important task in the fields of chemistry because it will lead to the preservation of the environment of the earth and will avoid wasting natural resources. We already reported that chiral phosphoric acid derived from (R)-BINOL functioned as an efficient chiral Bronsted acid catalyst. In this study, we developed efficient method for the preparation of a number of synthetically important intermediates which will be employed for the synthesis of biologically important compounds such as agrochemicals and pharmaceuticals.

Research Products

• [Journal Article] Chiral Phosphoric-Acid-Catalyzed Transfer Hydrogenation of Ethyl Ketimine Derivatives by Using Benzothiazoline (2014)
  • Author(s): Saito, K.; Horiguchi, K.; Shibata, Y.; Yamanaka, M.; Akiyama, T.
  • Journal Title: Chem. Eur. J. Volume: 20 Issue: 25 Pages: 7616-7620
  • DOI: 10.1002/chem.201402763
  • Peer Reviewed
• [Journal Article] Stereoselective Construction of All Carbon Quaternary Center by Means of Chiral Phosphoric Acid : Highly Enantioselective Friedel-Crafts Reaction of Indoles with β,β-Disubstituted Nitoroalkenes (2014)
  • Author(s): Mori, K.; Wakazawa, M.; Akiyama, T
  • Journal Title: Chem. Sci Volume: 5 Issue: 5 Pages: 1799-1803
  • DOI: 10.1039/c3sc53542h
  • Peer Reviewed
• [Journal Article] Enantioselective Fluorination of β-Ketoesters Catalyzed by Chiral Sodium Phosphate : Remarkable Enhancement of Reactivity by Simultaneous Utilization of Metal Enolate and Metal Phosphate (2014)
  • Author(s): Mori, K.; Miyake, A.; Akiyama, T
  • Journal Title: Chem. Lett Volume: 43 Issue: 1 Pages: 137-139
  • DOI: 10.1246/cl.130934
  • NAID: 130004427102
  • Peer Reviewed
• [Journal Article] Double C(sp3)-H Bond Functionalization Mediated by Sequential Hydride Shift/Cyclization Process: Diastereoselective Construction of Polyheterocycles (2014)
  • Author(s): Mori, K.; Kurihara, K.; Yabe, S.; Yamanaka, M.; Akiyama, T.
  • Journal Title: J. Am. Chem. Soc. Volume: 136 Issue: 10 Pages: 3744-3747
  • DOI: 10.1021/ja412706d
  • Peer Reviewed
• [Journal Article] Phosphoric Acid Bridged Cobalt Bis(dicarbollide) Ion as a Highly Efficient Catalyst for the Organocatalytic Hydrogenation of Ketimines (2014)
  • Author(s): Takahiko Akiyama, Kodai Saito, Slawomir Janczak, Zbigniew J. Lesnikowski
  • Journal Title: Synlett Volume: 25 Issue: 06 Pages: 795-798
  • DOI: 10.1055/s-0033-1340847
  • Peer Reviewed
• [Journal Article] Chiral Copper(II) Phosphate Catalyzed Enantioselective Synthesis of Isochromene Derivatives by Sequential Intramolecular Cyclization and Asymmetric Transfer Hydrogenation of o-Alkynylacetophenones (2013)
  • Author(s): Saito, K.; Kajiwara, Y.; Akiyama, T. Angew
  • Journal Title: Chem. Int. Ed Volume: 52 Issue: 50 Pages: 13284-13288
  • DOI: 10.1002/anie.201308303
  • Peer Reviewed
• [Journal Article] Enantioselective Transfer Hydrogenation of Difluoromethyl Ketimines Using Benzothiazoline as a Hydrogen Donor in Combination with Chiral Phosphoric Acid (2013)
  • Author(s): Sakamoto, T.; Horiguchi, K.; Saito, K.; Mori, K.; Akiyama, T.
  • Journal Title: Asian J. Org. Chem. Volume: 2 Issue: 11 Pages: 943-946
  • DOI: 10.1002/ajoc.201300174
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prediction of suitable catalyst by 1H NMR: asymmetric synthesis of multisubstituted biaryls by chiral phosphoric acid catalyzed asymmetric bromination (2013)
  • Author(s): Mori, K.; Ichikawa, Y.; Kobayashi, M.; Shibata, Y.; Yamanaka, M.; Akiyama, T.
  • Journal Title: Chem. Sci. Volume: 4 Issue: 11 Pages: 4235-4239
  • DOI: 10.1039/c3sc52142g
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chiral Phosphoric Acid Catalyzed Oxidative Kinetic Resolution of Indolines Based on Transfer Hydrogenation to Imines (2013)
  • Author(s): Saito, K.; Shibata, Y.; Yamanaka, M.; Akiyama, T.
  • Journal Title: J. Am. Chem. Soc. Volume: 135 Issue: 32 Pages: 11740-11743
  • DOI: 10.1021/ja406004q
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enantioselective Synthesis of Multisubstituted Biaryl Skeleton by Chiral Phosphoric Acid Catalyzed Desymmetrization/Kinetic Resolution Sequence (2013)
  • Author(s): Mori, K.; Ichikawa, Y.; Kobayashi, M.; Shibata, Y.; Yamanaka, M.; Akiyama, T.
  • Journal Title: J. Am. Chem. Soc. Volume: 135 Issue: 10 Pages: 3964-3970
  • DOI: 10.1021/ja311902f
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Kinetic Resolution in Chiral Brønsted Acid Catalyzed Aldol Reaction : Enantioselective Robinson-type Annulation Reaction (2012)
  • Author(s): Yamanaka, M.; Hoshino, M.; Katoh, T.; Mori, K.; Akiyama, T
  • Journal Title: Eur. J. Org. Chem Volume: 2012 Issue: 24 Pages: 4508-4514
  • DOI: 10.1002/ejoc.201200338
  • Peer Reviewed
• [Journal Article] Phosphoric Acid Catalyzed Enantioselective Transfer Deuteration of Ketimines by Use of Benzothiazoline as a Deuterium Donor : Synthesis of Optically Active Deuterated Amines (2012)
  • Author(s): Sakamoto, T.; Mori, K.; Akiyama, T
  • Journal Title: Org. Lett Volume: 14 Issue: 13 Pages: 3312-3315
  • DOI: 10.1021/ol3012869
  • Peer Reviewed
• [Journal Article] Enantioselective Organocatalytic Reductive Amination of Aliphatic Ketones by Benzothiazoline as Hydrogen Donor (2012)
  • Author(s): Saito, K.; Akiyama, T.
  • Journal Title: Chem. Commun Volume: 48 Issue: 38 Pages: 4573-4575
  • DOI: 10.1039/c2cc31486j
  • Peer Reviewed
• [Journal Article] Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation : A Facile Synthetic Access to Highly Optically Active Trifluoromethylated Amines (2011)
  • Author(s): Henseler, A.; Kato, M.; Mori, K.; Akiyama, T
  • Journal Title: Angew. Chem. Int. Ed Volume: 50 Issue: 35 Pages: 8180-8183
  • DOI: 10.1002/anie.201103240
  • Peer Reviewed
• [Journal Article] Selective Activation of Enantiotopic C(sp3)-Hydrogen by Means of Chiral Phosphoric Acid: Asymmetric Synthesis of Tetrahydroquinoline Derivatives (2011)
  • Author(s): Mori, K.; Ehara, K.; Kurihara, K.; Akiyama, T. J
  • Journal Title: Am. Chem. Soc Volume: 133 Issue: 16 Pages: 6166-6169
  • DOI: 10.1021/ja2014955
  • Peer Reviewed
• [Journal Article] Chiral Phosphoric Acid Catalyzed Enantioselective Synthesis of β-Amino-α,α-difluoro Carbonyl Compounds (2011)
  • Author(s): Kashikura, W.; Mori, K.; Akiyama, T
  • Journal Title: Org. Lett Volume: 13 Issue: 7 Pages: 1860-1863
  • DOI: 10.1021/ol200374m
• [Journal Article] Expeditious Construction of a Carbobicyclic Skeleton via a sp3-C-H Functionalization: Hydride Shift from an Aliphatic Tertiary Position in an Internal Redox Process (2011)
  • Author(s): Mori, K.; Sueoka, S.; Akiyama T
  • Journal Title: J. Am. Chem. Soc Volume: 133 Issue: 8 Pages: 2424-2426
  • DOI: 10.1021/ja110520p
  • Peer Reviewed
• [Presentation] Oxidative Kinetic Resolution of Indolines based on Transfer Hydrogenation to Ketimines by means of Chiral Phosphoric Acid (2013)
  • Author(s): Akiyama, T.; Saito, K
  • Organizer: International Symposium on Catalysis and Fine Chemicals 2013 (C&FC 2013), (Renmin University of China)
  • Place of Presentation: Beijing, China
• [Presentation] Oxidative Kinetic Resolution of Indolines base on Transfer Hydrogenation of Ketimines by means of Chiral Phoshoric Acid (2013)
  • Author(s): Akiyama, T.; Saito, K
  • Organizer: The 11th International Symposium on Organic Reactions (ISOR 2011 Taipei)
  • Place of Presentation: Taipei, Taiwan
• [Presentation] キラルブレンステッド酸触媒反応の新展開 (2013)
  • Author(s): 秋山隆彦
  • Organizer: 第30回有機合成セミナー
  • Place of Presentation: 瀬戸内児島ホテル ,倉敷, 岡山
• [Presentation] Enantioselective Transfer Hydrogenation of Ketimines by Use of Benzothiazoline as a Hydrogen Donor (2013)
  • Author(s): 秋山隆彦
  • Organizer: 文部科学省科学研究費補助金「新学術領域研究(研究領域提案型)」「有機分子触媒による未来型分子変換」第1回国際会議(兼)第6回有機触媒シンポジウム
  • Place of Presentation: 大津プリンスホテル, 大津
• [Presentation] キラルブレンステッド酸触媒を用いた不斉合成反応 (2013)
  • Author(s): 秋山隆彦
  • Organizer: Symposium on Molecular Chirality 2013,第20回記念シンポジウム モレキュラー・キラリティー2013
  • Place of Presentation: 京都大学, 京都
• [Presentation] キラルブレンステッド酸触媒を用いた不斉合成反応 (2013)
  • Author(s): 秋山隆彦
  • Organizer: モレキュラー・キラリティー2013
  • Place of Presentation: 京都
  • Invited
• [Presentation] キラルブレンステッド酸触媒反応の新展開 (2013)
  • Author(s): 秋山隆彦
  • Organizer: 有機合成化学協会関東支部ミニシンポジウムつくば2013
  • Place of Presentation: 筑波大学
  • Invited
• [Presentation] キラルブレンステッド酸触媒反応の新展開 (2013)
  • Author(s): 秋山隆彦
  • Organizer: 有機合成化学協会関西支部有機合成夏期セミナー
  • Place of Presentation: 大阪科学技術センター
  • Invited
• [Presentation] キラルブレンステッド酸触媒反応の新展開 (2013)
  • Author(s): 秋山隆彦
  • Organizer: 第30回有機合成セミナー
  • Place of Presentation: せとうち児島ホテル
  • Invited
• [Presentation] Oxidative Kinetic Resolution of Indolines based on Transfer Hydrogenation to Ketimines by means of Chiral Phosphoric Acid (2013)
  • Author(s): Takahiko Akiyama, Kodai Saito
  • Organizer: International Symposium on Organic Reactions 2013 (ISOR 2013),
  • Place of Presentation: Taipei, Taiwan
  • Invited
• [Presentation] Oxidative Kinetic Resolution of Indolines based on Transfer Hydrogenation to Ketimines by means of Chiral Phosphoric Acid (2013)
  • Author(s): Takahiko Akiyama and Kodai Saito
  • Organizer: International Symposium on Catalysis and Fine Chemicals 2013 (C&FC 2013)
  • Place of Presentation: Beijing, China
  • Invited
• [Presentation] Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation of Trifluorimethylated Ketimines (2013)
  • Author(s): Takahiko Akiyama
  • Organizer: 21st Winter Fluorine Conference(招待講演)
  • Place of Presentation: St. Pete Beach, Florida, USA
  • Invited
• [Presentation] Enantioselective Transfer Hydrogenation by Use of Benzothiazoline (2012)
  • Author(s): Akiyama, T.
  • Organizer: Japan-US Organocatalytic Symposium in Hawaii 2012
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2012-12-17
• [Presentation] キラルリン酸触媒による非対称化/速度論的光学分割を伴う不斉臭素化反応を鍵とする光学活性ビアリールの不斉合成研究 (2012)
  • Author(s): 森啓二・市川夕貴・小林真奈人・柴田幸大・山中正浩・秋山隆彦
  • Organizer: 第101回有機合成シンポジウム
  • Place of Presentation: 東京(慶應義塾大学薬学部)
• [Presentation] Enantioselective Synthesis of Organofluorine Compounds by Means of Chiral Brønsted Acid Catalyt (2012)
  • Author(s): Takahiko Akiyama
  • Organizer: Valencia Fluorine Days(招待講演)
  • Place of Presentation: Valencia, Spain
  • Invited
• [Presentation] Enantioselective Transfer Hydrogenation of Ketimines by Use of Benzothiazoline as a Novel Hydrogen Donor (2012)
  • Author(s): Takahiko Akiyama
  • Organizer: Cambodian Malaysian Chemical Conference (CMCC) 2012(招 待講演)
  • Place of Presentation: Siem Reap, Cambodia
  • Invited
• [Presentation] キラルリン酸触媒を用いた不斉合成反応の新展開 (2012)
  • Author(s): 秋山隆彦
  • Organizer: 有機合成化学協会九州山口支部平成24年度有機合成化学講 演会(招待講演)
  • Place of Presentation: 北九州
  • Invited
• [Presentation] Enantioselective Transfer Hydrogenation by Use of Benzothiazoline (2012)
  • Author(s): Takahiko Akiyama
  • Organizer: Japan-US Organocatalytic Symposium in Hawaii (2012)(招待 講演)
  • Place of Presentation: Honolulu, Hawaii
  • Invited
• [Presentation] Enantioselective Synthesis of Organofluorine Compounds by Means of Chiral Brønsted Acid Catalyt (2012)
  • Author(s): Takahiko Akiyama
  • Organizer: Valencia Fluorine Days
  • Place of Presentation: Valencia, Spain
  • Invited
• [Presentation] Enantioselective Transfer Hydrogenation of Ketimines by Use of Benzothiazoline as a Novel Hydrogen Donor (2012)
  • Author(s): Takahiko Akiyama
  • Organizer: Cambodian Malaysian Chemical Conference (CMCC) 2012
  • Place of Presentation: Siem Reap, Cambodia
  • Invited
• [Presentation] キラルリン酸触媒を用いた不斉合成反応の新展開 (2012)
  • Author(s): 秋山隆彦
  • Organizer: 有機合成化学協会九州山口支部平成24年度有機合成化学講演会
  • Place of Presentation: 北九州
  • Invited
• [Presentation] Enantioselective Transfer Hydrogenation by Use of Benzothiazoline (2012)
  • Author(s): Takahiko Akiyama
  • Organizer: Japan-US Organocatalytic Symposium in Hawaii (2012)
  • Place of Presentation: Honolulu, Hawaii
  • Invited
• [Presentation] Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation of Trifluorimethylated Ketimines (2012)
  • Author(s): Takahiko Akiyama
  • Organizer: 21st Winter Fluorine Conference
  • Place of Presentation: St. Pete Beach, Florida, USA
  • Invited
• [Presentation] Enantioselective Transfer Hydrogenation of Ketimines by Means of Benzothiazoline as Novel Hydrogen Donor (2011)
  • Author(s): Akiyama, T
  • Organizer: International Symposium on Catalysis and Fine Chemicals 2011 (C&FC2011). Nara Prefectual New Public Hall
  • Place of Presentation: Nara
  • Year and Date: 2011-12-08
• [Presentation] Recent Progress in the Chiral Phosphoric Acid Catalyzed Reactions (2011)
  • Author(s): Akiyama, T
  • Organizer: 10th International Symposium on Organic Reactions (ISOR 10). Keio University
  • Place of Presentation: Yokohama
  • Year and Date: 2011-11-24
• [Presentation] Chiral Phosphoric Acid Catalyzed C(sp3)-H Bond Activation" (2011)
  • Author(s): Akiyama, T.
  • Organizer: First German-Japan Organocatalytic Symposium
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-10-15
• [Presentation] Chiral Phosphoric Acid Catalyzed C(sp3)-H Bond Activation (2011)
  • Author(s): Takahiko Akiyama
  • Organizer: First German-Japan Organocatalytic Symposium
  • Place of Presentation: 京都
  • Invited
• [Presentation] Recent Progress in the Chiral Phosphoric Acid Catalyzed Reactions (2011)
  • Author(s): Takahiko Akiyama
  • Organizer: 10th International Symposium on Organic Reactions (ISOR 10)
  • Place of Presentation: 横浜
  • Invited
• [Presentation] Enantioselective Transfer Hydrogenation of Ketimines by Means of Benzothiazoline as Novel Hydrogen Donor (2011)
  • Author(s): Takahiko Akiyama
  • Organizer: International Symposium on Catalysis and Fine Chemicals 2011 (C&FC2011)
  • Place of Presentation: 奈良
  • Invited
• [Presentation] Oxidative Kinetic Resolution of Indolines based on Transfer Hydrogenation to Ketimines by means of Chiral Phosphoric Acid
  • Author(s): Akiyama, T.
  • Organizer: Asymmetric Synthesis Conference (Zing Conference)
  • Place of Presentation: Nerja, Spain
• [Presentation] Development of Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid
  • Author(s): Akiyama T.
  • Organizer: Indo-Japanese Conference on Process Chemistry R&D
  • Place of Presentation: Juhu Mumbai, India
• [Book] The Bimolecular and Intramolecular Mannich and Related Reactions, in Comprehensive Organic Synthesis, 2nd Edition, Volume 2, Edited by Molander, G. A.; Knochel, P. Oxford (2014)
  • Author(s): Akiyama, T
  • Publisher: Elsevier
• [Book] Brønsted Acids : Chiral Phosphoric Acid Catalys in Asymmetric Synthesis, in Volume 2, Comprehensive Enantioselecitve Organocatalysis, Edited by Dalko, P. I. Wiley-VCH (2013)
  • Author(s): Mori, K.; Akiyama, T.
  • Publisher: Weinheim, Germany
• [Book] Phosphoric Acid Catalyzed Reactions of Imines, Section 2.1.1. Asymmetric Organocatalysis, Science of Synthesis, Edited by Maruoka, K. Georg Thime Verlag KG (2012)
  • Author(s): Akiyama, T
  • Publisher: Stuttgart, Germany
• [Book] Synthesis without Metals, in "Handbook of Green Chemistry, Edited by Li, C.-J. Wiley-VCH (2012)
  • Author(s): Akiyama, T
  • Publisher: Weinheim, Germany
• [Book] Asymmetric C-C Bond Formation Using Chiral Phoshoric Acid, in Asymetric Synthesis II, Edited by Christmann, M.; Bräse, S. Wiley-VCH (2012)
  • Author(s): Akiyama, T
  • Publisher: Weinheim, Germany
• [Book] 6.3 C-C Bond Formation : Mannich Reaction, in Volume 6: Synthetic Methods V -Organocatalysis, Comprehensive Chirality, Edited by Maruoka, K. (2012)
  • Author(s): Akiyama, T
  • Publisher: Elsevier
• [Book] Georg Thime Verlag KG (2012)
  • Author(s): Takahiko Akiyama
  • Publisher: Section 2.1.1. Asymmetric Organocatalysis, Science of Synthesis, Edited by Keiji Maruoka,
• [Book] Wiley-VCH (2012)
  • Author(s): Takahiko Akiyama
  • Publisher: Synthesis without Metals, in "Handbook of Green Chemistry
• [Book] Wiley-VCH (2012)
  • Author(s): Takahiko Akiyama
  • Publisher: C-C Bond Formation Using Chiral Phoshoric Acid, in Asymetric Synthesis II
• [Book] Elsevier (2012)
  • Author(s): Takahiko Akiyama
  • Publisher: C-C Bond Formation : Mannich Reaction, in Volume 6: Synthetic Methods V -Organocatalysis, Comprehensive Chirality
• [Remarks]
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• [Remarks] 学習院大学理学部化学科秋山研究室
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