Structure of reactive aggregate of lithium reagents and its application to the generation of highly-activated reagents.

• Project/Area Number: 20790007
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: YAMAMOTO Yasutomo Kyoto University, 薬学部, 助教 (10452278)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 有機リチウム / NMR / 構造解析 / 多成分錯体 / 不斉反応

Research Abstract

Organolithiums are one of the most frequently-used reagents in synthetic chemistry. To better understand their reactivity and reaction mechanisms, it is necessary to elucidate the structure of reactive organolithium reagents. We found that a ternary complex reagent of lithium ester enolate-chiral diether-lithium diisopropylamide was formed in an equimolar mixture of these reagents in toluene based on low-temperature NMR spectroscopy. This complex shows high reactivity and enantioselectivity in an asymmetric Michael reaction.

Research Products

• [Journal Article] Rhodium-Catalyzed Asymmetric Phenylation of N-Phosphinoylarylimines with Triphenylborane (2011)
  • Author(s): Xinyu Hao
  • Journal Title: Catal.Sci.Tech. Volume: 1 Pages: 62-64
  • Peer Reviewed
• [Journal Article] NMR Studies of a Ternary Complex Reagent of Lithium Ester Enolate, Chiral Diether, and Lithium Diisopropylamide in an Asymmetric Michael Reaction. (2010)
  • Author(s): Yasutomo Yamamoto, Yorinobu Yasuda, Hassan Oulyadi, Jacques Maddaluno, Kiyoshi Tomioka
  • Journal Title: Tetrahedron 66(13) Pages: 2470-2473
  • Peer Reviewed
• [Journal Article] Stereoselective Formal Synthesis of (+)-Allokainic Acid via Thiol-mediated Acyl Radical Cyclization. (2010)
  • Author(s): Ken-ichi Yamada
  • Journal Title: Chem.Pharm.Bull. Volume: 58 Pages: 1511-1516
  • Peer Reviewed
• [Journal Article] NMR Studies of a Ternary Complex Reagent of Lithium Ester Enolate, Chiral Diether, and Lithium Diisopropylamide in an Asymmetric Michael Reaction (2010)
  • Author(s): 山本康友, 安田順信, Hassan Oulyadi, Jacques Maddaluno, 富岡清
  • Journal Title: Tetrahedron 66 Pages: 2470-2473
  • Peer Reviewed
• [Journal Article] Asymmetric Construction of Binaphthyl by the Chiral Diether-Mediated Conjugate Addition of Naphthyllithium to Naphthalenecarboxylic Acid BHA Ester. (2009)
  • Author(s): Mitsuru Shindo, Yasutomo Yamamoto, Ken-ichi Yamada, Kiyoshi Tomioka
  • Journal Title: Chem.Pharm.Bull. 57(7) Pages: 752-754
  • Peer Reviewed
• [Journal Article] Asymmetric Construction of Three Contiguous Stereogenic Centers by Conjugate Addition-Alkylation of Lithium Ester Enolate. (2009)
  • Author(s): Yasutomo Yamamoto, Yorinobu Yasuda, Hiroyuki Nasu, Kiyoshi Tomioka
  • Journal Title: Org.Lett. 11(9) Pages: 2007-2009
  • Peer Reviewed
• [Journal Article] Enantioselective Conjugate Addition of a Lithium Ester Enolate Catalyzed by Chiral Lithium Amides : a Possible Intermediate Characterized. Baptiste Lecachey, Nicolas Duguet, Hassan Oulyadi, Catherine Fressigne, Anne Harrison-Marchand (2009)
  • Author(s): Yasutomo Yamamoto, Kiyoshi Tomioka, Jacques Maddaluno
  • Journal Title: Org.Lett. 11(9) Pages: 1907-1910
  • Peer Reviewed
• [Journal Article] Asymmetric Construction of Quaternary Carbon Centers by Sequential Conjugate Addition of Lithium Amide and in situ Alkylation : Utility in the Synthesis of (-)-Aspidospermidine. (2009)
  • Author(s): Mayuko Suzuki, Yoshito Kawamoto, Takeo Sakai, Yasutomo Yamamoto, Kiyoshi Tomioka
  • Journal Title: Org.Lett. 11(3) Pages: 653-655
  • Peer Reviewed
• [Journal Article] Aminolithiation of Carbon-Carbon Double Bonds as A Powerful Tool in Organic Synthesis. (2009)
  • Author(s): Kiyoshi Tomioka, Takeo Sakai, Tokutaro Ogata, Yasutomo Yamamoto
  • Journal Title: Pure Appl.Chem. 81(2) Pages: 247-253
  • Peer Reviewed
• [Journal Article] Asymmetric Construction of Three Contiguous Stereogenic Centers by Conjugate Addition-Alkylation of Lithium Ester Enolate (2009)
  • Author(s): 山本康友, 安田順信, 那須裕之, 富岡清
  • Journal Title: Organic Letters 11 Pages: 2007-2009
  • Peer Reviewed
• [Journal Article] Aminolithiation of Carbon-Carbon Double Bonds as A Powerful Tool in Organic Synthesis (2009)
  • Author(s): 富岡清, 坂井健男, 尾形篤太郎, 山本康友
  • Journal Title: Pure and Applied Chemistry 81 Pages: 247-253
  • Peer Reviewed
• [Journal Article] Consecutive Cyclization of Allylaminoalkene by Intramolecular Aminolithiation-Carbolithiation. (2008)
  • Author(s): Susumu Tsuchida, Atsunori Kaneshige, Tokutaro Ogata, Hiromi Baba, Yasutomo Yamamoto, Kiyoshi Tomioka
  • Journal Title: Org.Lett. 10(16) Pages: 3635-3638
  • Peer Reviewed
• [Journal Article] A Ternary Complex Reagent for An Asymmetric Michael Reaction of Lithium Ester Enolates with Enoates. (2008)
  • Author(s): Yasutomo Yamamoto, Hirokazu Suzuki, Yorinobu Yasuda, Kiyoshi Tomioka
  • Journal Title: Tetrahedron Lett. 49(31) Pages: 4582-4584
  • Peer Reviewed
• [Journal Article] A ternary complex reagent_for an asymmetric Michael reaction of lithium ester enolates with enoates (2008)
  • Author(s): 山本康友, 鈴木寛和, 安田順信, 飯田彰, 富岡清
  • Journal Title: Tetrahedron Letters 49 Pages: 4582-4584
  • Peer Reviewed
• [Presentation] リチウムアミド-キラルジエーテル複合反応剤のNMR構造 (2011)
  • Author(s): 山本康友
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] NMR Studies of a Ternary Complex Reagent of Lithium Ester Enolate, Chiral Diether, and Lithium Diisopropylamide in an Asymmetric Michael Reaction (2010)
  • Author(s): 山本康友
  • Organizer: Pacifichem 2010
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2010-12-16
• [Presentation] NMR Studies of a Ternary Complex Reagent of Lithium Ester Enolate, Chiral Diether, and Lithium Diisopropylamide in an Asymmetric Michael Reaction (2010)
  • Author(s): 山本康友
  • Organizer: Pacifichem2010
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2010-12-16
• [Presentation] 高活性複合系リチウム反応剤の不斉共役付加反応と構造研究 (2010)
  • Author(s): 山本康友
  • Organizer: 第60回日本薬学会近畿支部総会・大会(支部会奨励賞受賞者講演)
  • Place of Presentation: 摂南大学
  • Year and Date: 2010-10-30
• [Presentation] 高活性複合系リチウム反応剤の不斉共役付加反応と構造研究 (2010)
  • Author(s): 山本康友
  • Organizer: 第60回日本薬学会近畿支部総会・大会
  • Place of Presentation: 摂南大学(支部会奨励賞受賞者講演)
  • Year and Date: 2010-10-30
• [Presentation] 高活性複合系リチウム反応剤の不斉Michael付加反応と構造研究 (2009)
  • Author(s): 山本康友
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2009-11-17
• [Presentation] 高活性複合系リチウム反応剤の不斉Michael付加反応と構造研究 (2009)
  • Author(s): 山本康友
  • Organizer: 第59回日本薬学会近畿支部大会
  • Place of Presentation: 近畿大学
  • Year and Date: 2009-10-24
• [Presentation] 4級炭素の不斉構築を鍵とする(一)-Aspidospermidine の不斉全合成 (2009)
  • Author(s): 山本康友
  • Organizer: 第51回天然有機化合物討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-10-07
• [Presentation] リチウムエステルエノラート三成分反応剤の高選択的不斉Michael付加反応 (2008)
  • Author(s): 山本康友
  • Organizer: 第58回日本薬学会近畿支部大会
  • Place of Presentation: 神戸薬科大学
  • Year and Date: 2008-10-25
• [Presentation] A Ternary Complex Reagent for An Asymmetric Michael Reaction of Lithium Ester Enolates with Enoates (2008)
  • Author(s): 山本康友
  • Organizer: The 20th French-Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: Bordeaux, France
  • Year and Date: 2008-09-08
• [Presentation] A ternary complex reagent for-an asymmetric Michael reaction of lithium ester enolates with enoates (2008)
  • Author(s): 山本康友, 鈴木寛和, 安田順信, 富岡清
  • Organizer: 20th French-Japanese Symposium on Medicinal and Fine Chemistry
  • Place of Presentation: Bordeaux, France
  • Year and Date: 2008-09-08
• [Presentation] A Ternary Complex Reagent for An Asymmetric Michael Reaction of Lithium Ester Enolates with Enoates (2008)
  • Author(s): 山本康友
  • Organizer: The First international Symposium on Process Chemistry
  • Place of Presentation: 京都国際会館
  • Year and Date: 2008-07-30
• [Presentation] A ternary complex reagent for an asymmetric Michael reaction of lithium ester enolates with enoates (2008)
  • Author(s): 山本康友, 鈴木寛和, 安田順信, 富岡清
  • Organizer: 第1回プロセス化学国際シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-07-30
• [Presentation] A ternary complex reagent for an asymmetric Michael reaction of lithium ester enolates with enoates (2008)
  • Author(s): 山本康友, 鈴木寛和, 安田順信, 富岡清
  • Organizer: 17th International Conference on Organic Synthesis (ICOS 17)
  • Place of Presentation: Daejeon, Korea
  • Year and Date: 2008-06-24
• [Presentation] A Ternary Complex Reagent for An Asymmetric Michael Reaction of Lithium Ester Enolates with Enoates
  • Author(s): 山本康友
  • Organizer: 17th International Conference on Organic Chemistry
  • Place of Presentation: Daejeon, Korea
• [Book] 使える!有機合成反応241実践ガイド (2010)
  • Author(s): 山本康友(分担執筆)
  • Publisher: 化学同人
• [Book] 使える!有機合成反応241 実践ガイド (2010)
  • Author(s): 山本康友
  • Publisher: 化学同人