1998 年度実績報告書

多段階ワンポットプロセスの開発と天然物の触媒的不斉合成への応用

研究課題

研究課題/領域番号	10125207
研究機関	東京大学
研究代表者	柴崎正勝東京大学, 大学院・薬学系研究科, 教授 (30112767)
研究分担者	金井求東京大学, 大学院・薬学系研究科, 助手 (20243264) 飯田剛彦東京大学, 大学院・薬学系研究科, 助手 (40292958)
キーワード	触媒的不斉ヘック反応 / PI3キナーゼ阻害剤 / ワートマンニン / Tol-BINAP-パラジウム錯体 / 速度論的分割 / 相対配置 / 鈴木クロスカップリング / ワンポット触媒的不斉プロセス
研究概要	触媒的不斉ヘック反応を鍵工程とする、PI3キナーゼ阻害剤ワートマンニンの不斉全合成を目的として研究を行った。その結果20mol%のTol-BINAP-パラジウム錯体の制御によりラセミ体原料の速度論的分割が高エナンチオ選択的に進行し、鍵中間体であるヘック反応成績体力96%eeで得られることを見出した。すなわち、ラセミ体原料を20mol%の酢酸パラジウム、40mol%のTol-BINAP、250mol%の炭酸カリウムの存在下、トルエン溶媒中100度で反応させることにより、分子内ヘック反応の進行した3環性鍵中間体が収率20%、96%ee、ジアステレオ選択性11:1で得られた。本反応は触媒的不斉ヘック反応を速度論的分割に応用したはじめての例であり、さらに相対配置までを高度に選択している点で評価される。今後、鈴木クロスカップリング反応と組み合わせて鈴木クロスカップリング-ヘックワンポット触媒的不斉プロセスの開発により、より高効率な合成法を確立すると同時に、ワートマンニンの全合成に向けて研究を続けていく予定である。

研究成果

(27件)

すべてその他

すべて文献書誌 (27件)

[文献書誌] T.Arai,H.Sasai,K.Yamaguchi and M.Shibasaki: "Regioselective Catalytic Asymmetric Reation of Horner-Wadsworth-Emmons Reagents with Enones:The Odyssey of Chiral Aluminum Catalysts" J.Am.Chem.Soc.120. 441-442 (1998)
[文献書誌] M.Sodeoka,M.A.Arai,K.Adachi,K.Uotsu and M.Shibasaki: "Rational Design,Synthesis,and Evaluation of a New Type of PKC inhibitor" J.Am.Chem.Soc.120. 457-458 (1998)
[文献書誌] S.Y.Cho and M.Shibasaki: "Synthesis and Evaluation of a New Chiral Ligand:2-diphenylarsino-2´-diphenylphosphino-1,1´-binaphthyl(BINAPAs)" Tetrahedron Lett.39. 1773-1776 (1998)
[文献書誌] A.Kojima,T.Takemoto,M.Sodeoka and M.Shibasaki: "Catalytic Asymmetric Sythesis of Halenaquinone and Halenaquinol" Synthesis. 581-589 (1998)
[文献書誌] H.Groger,Y.Saida,H.Sasai,K.Yamaguchi,J.Martens and M.Shibasaki: "A New and Highly Efficient Asymmetric Route to Cyclic α-Amino Phosphonates:The First Catalytic Enantioselective Hydrophosphonylation of Cyclic Imines Catalyzed by Chiral Heterobimetallic Lanthanoid" J.Am.Chem.Soc.120. 3089-3103 (1998)
[文献書誌] E.Emori,T.Arai,H.Sasai and M.Shibasaki: "A Catalytic Michael Addition of Thiols to α,β-Unsaturated Carbonyl Compounds:Asymmetric Protonations" J.Am.Chem.Soc.120. 4043-4044 (1998)
[文献書誌] M.Shibasaki,T.Iida,Y.M.A.Yamada: "Development of Multifunctional Asymmetric Catalysts and Their Application to Practical Organic Synthesis" 有機合成化学協会誌. 56. 344-356 (1998)
[文献書誌] T.Morita,T.Arai,H.Sasai and M.Shibasaki: "Utilization of heterobimetallic complexes as Lewis acids" Tetrahedron:Asymmetry. 9. 1445-1450 (1998)
[文献書誌] M.Sodeoka and M.Shibasaki: "Asymmetric synthesis using palladium catalysts" Pure & Appl.Chem.70. 411-414 (1998)
[文献書誌] K.Yamada,Y.Arai,H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of II-Deoxy-PGF_<1α> Using ALB,a Heterobimetallic Multifunctional Asymmetric Complex" J.Org.Chem.63. 3666-3672 (1998)
[文献書誌] Y.M.A.Yamada and M.Shibasaki: "Direct Catalytic Asymmetric Aldol Reactions Promoted by a Novel Barium Complex" Tetrahedron Letters.39. 5561-5564 (1998)
[文献書誌] M.Shibasaki,H.Sasai,T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)
[文献書誌] M.Shibasaki and K.Uotsu: "PKC activations and inhibitors" IGAKUSHOIN. 49. 290-295 (1998)
[文献書誌] K.Uotsu,M.Sodeoka and M.Shibasaki: "Photoaffinity Labeling of PKC lsozymes by Phorbol Ester Derivatives" Bioorg.& Med.Chem.6. 1117-1126 (1998)
[文献書誌] H.Groes,E.M.Vogl and M.Shibasaki: "New Catalytic Concepts for the Asymmetric Aldol Reation" Chem.Eur.J.4. 1137-1141 (1998)
[文献書誌] T.Iida,N.Yamamoto,H.-G.Woo and M.Shibasaki: "Enantioselective Ring Opening of Epoxides with 4-Methoxyphenol Catalyzed by Gallium Heterobimetallic Complexes:An Efficient Method for the Synthesis of Optically Active 1,2-Diol Monoethers" Angew.Chem.Int.Ed.Engl.37. 2223-2226 (1998)
[文献書誌] M.Shibasaki,H.Sasai T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)
[文献書誌] E.M.Vogl,S.Matsunaga,M.Kanai,T.Iida and M.Shibasaki: "Linking BINOL:C_2-Symmetric Ligands for Investigations on Asymmetric Catalysis" Tetrahedron Letters. 39. 7917-7920 (1998)
[文献書誌] F.Miyazaki,K.Uotsu and M.Shibasaki: "Silver Salt Effects on an Asymmetric Heck Reation.Catalytic Asymmetric Total Synthesis of (+)-Xestoquinone." Tetrahedron. 54. 13073-13078 (1998)
[文献書誌] S.Shimizu,K.Ohori,T.Arai,H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of Tubifolidine" J.Org.Chem.63. 7547-7551 (1998)
[文献書誌] K.Funabashi,Y.Saida,M.Kanai.T.Arai,H.Sasai and M.Shibasaki: "Catalytic Asymmetric Michael Adition of Nitromethane to Enones Controlled by (R)-LPB" Tetrahedron Letters. 39. 7557-7558 (1998)
[文献書誌] S.Watanabe,Y.Kobayashi,T.Arai,H.Sasai,M.Bougauchi and M.Shibasaki: "Water vs.Desiccant.Improvement of Yb-BINOL Complex Catalyzed Enantioselective Epoxidation of Enones" Tetrahedron Letters. 39. 7353-7356 (1998)
[文献書誌] M.Shibasaki,A.Kojima and S.Shimizu: "Catalytic Asymmetric Synthesis of Natural Products with Heterocyclic Rings" J.Heterocyclic Chem.35. 1057-1064 (1998)
[文献書誌] S.Watanabe,T.Arai,H.Sasai,M.Bougauchi and M.Shibasaki: "The First Catalytic Enatioselective Synthesis of cis-Epoxyketones from cis-Enones" J.Org.Chem.63. 8090-8091 (1998)
[文献書誌] S,Y.Cho and M.Shibasaki: "The symmetric of cyclopentane derivatives by palladium-catalyzed coupling of prochiral alkylboron" Tetrahedron:Asymmetry. 9. 3751-3754 (1998)
[文献書誌] S.Yamasaki,T.Iida and M.Shibasaki: "Direct Catalytic Asymmetric Mannich-type Reaction of Unmodified Ketones Utilizing the Cooperation of an AlLibis(binaphthoxide) Complex and La(OTY), nH_2O" Tetrahedron Lett.40. 307-310 (1999)
[文献書誌] S.Honzawa,T.Mizutani and M.Shibasaki: "Synthetic Studies on (+)-Wortmannin An Asymmetric Construction of an Allylic Quaternary Carbon Center by a Heck Reaction" Tetrahedron Lett.40. 311-314 (1999)

1998 年度 実績報告書

多段階ワンポットプロセスの開発と天然物の触媒的不斉合成への応用

研究代表者

柴崎 正勝 東京大学, 大学院・薬学系研究科, 教授 (30112767)

研究成果

[文献書誌] T.Arai,H.Sasai,K.Yamaguchi and M.Shibasaki: "Regioselective Catalytic Asymmetric Reation of Horner-Wadsworth-Emmons Reagents with Enones:The Odyssey of Chiral Aluminum Catalysts" J.Am.Chem.Soc.120. 441-442 (1998)

[文献書誌] M.Sodeoka,M.A.Arai,K.Adachi,K.Uotsu and M.Shibasaki: "Rational Design,Synthesis,and Evaluation of a New Type of PKC inhibitor" J.Am.Chem.Soc.120. 457-458 (1998)

[文献書誌] S.Y.Cho and M.Shibasaki: "Synthesis and Evaluation of a New Chiral Ligand:2-diphenylarsino-2´-diphenylphosphino-1,1´-binaphthyl(BINAPAs)" Tetrahedron Lett.39. 1773-1776 (1998)

[文献書誌] A.Kojima,T.Takemoto,M.Sodeoka and M.Shibasaki: "Catalytic Asymmetric Sythesis of Halenaquinone and Halenaquinol" Synthesis. 581-589 (1998)

[文献書誌] E.Emori,T.Arai,H.Sasai and M.Shibasaki: "A Catalytic Michael Addition of Thiols to α,β-Unsaturated Carbonyl Compounds:Asymmetric Protonations" J.Am.Chem.Soc.120. 4043-4044 (1998)

[文献書誌] M.Shibasaki,T.Iida,Y.M.A.Yamada: "Development of Multifunctional Asymmetric Catalysts and Their Application to Practical Organic Synthesis" 有機合成化学協会誌. 56. 344-356 (1998)

[文献書誌] T.Morita,T.Arai,H.Sasai and M.Shibasaki: "Utilization of heterobimetallic complexes as Lewis acids" Tetrahedron:Asymmetry. 9. 1445-1450 (1998)

[文献書誌] M.Sodeoka and M.Shibasaki: "Asymmetric synthesis using palladium catalysts" Pure & Appl.Chem.70. 411-414 (1998)

[文献書誌] K.Yamada,Y.Arai,H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of II-Deoxy-PGF_<1α> Using ALB,a Heterobimetallic Multifunctional Asymmetric Complex" J.Org.Chem.63. 3666-3672 (1998)

[文献書誌] Y.M.A.Yamada and M.Shibasaki: "Direct Catalytic Asymmetric Aldol Reactions Promoted by a Novel Barium Complex" Tetrahedron Letters.39. 5561-5564 (1998)

[文献書誌] M.Shibasaki,H.Sasai,T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)

[文献書誌] M.Shibasaki and K.Uotsu: "PKC activations and inhibitors" IGAKUSHOIN. 49. 290-295 (1998)

[文献書誌] K.Uotsu,M.Sodeoka and M.Shibasaki: "Photoaffinity Labeling of PKC lsozymes by Phorbol Ester Derivatives" Bioorg.& Med.Chem.6. 1117-1126 (1998)

[文献書誌] H.Groes,E.M.Vogl and M.Shibasaki: "New Catalytic Concepts for the Asymmetric Aldol Reation" Chem.Eur.J.4. 1137-1141 (1998)

[文献書誌] T.Iida,N.Yamamoto,H.-G.Woo and M.Shibasaki: "Enantioselective Ring Opening of Epoxides with 4-Methoxyphenol Catalyzed by Gallium Heterobimetallic Complexes:An Efficient Method for the Synthesis of Optically Active 1,2-Diol Monoethers" Angew.Chem.Int.Ed.Engl.37. 2223-2226 (1998)

[文献書誌] M.Shibasaki,H.Sasai T.Arai and T.Iida: "Heterobimetallic asymmetric catalysts Developments and applications" Pure & Appl.Chem.70. 1027-1034 (1998)

[文献書誌] E.M.Vogl,S.Matsunaga,M.Kanai,T.Iida and M.Shibasaki: "Linking BINOL:C_2-Symmetric Ligands for Investigations on Asymmetric Catalysis" Tetrahedron Letters. 39. 7917-7920 (1998)

[文献書誌] F.Miyazaki,K.Uotsu and M.Shibasaki: "Silver Salt Effects on an Asymmetric Heck Reation.Catalytic Asymmetric Total Synthesis of (+)-Xestoquinone." Tetrahedron. 54. 13073-13078 (1998)

[文献書誌] S.Shimizu,K.Ohori,T.Arai,H.Sasai and M.Shibasaki: "A Catalytic Asymmetric Synthesis of Tubifolidine" J.Org.Chem.63. 7547-7551 (1998)

[文献書誌] K.Funabashi,Y.Saida,M.Kanai.T.Arai,H.Sasai and M.Shibasaki: "Catalytic Asymmetric Michael Adition of Nitromethane to Enones Controlled by (R)-LPB" Tetrahedron Letters. 39. 7557-7558 (1998)

[文献書誌] S.Watanabe,Y.Kobayashi,T.Arai,H.Sasai,M.Bougauchi and M.Shibasaki: "Water vs.Desiccant.Improvement of Yb-BINOL Complex Catalyzed Enantioselective Epoxidation of Enones" Tetrahedron Letters. 39. 7353-7356 (1998)

[文献書誌] M.Shibasaki,A.Kojima and S.Shimizu: "Catalytic Asymmetric Synthesis of Natural Products with Heterocyclic Rings" J.Heterocyclic Chem.35. 1057-1064 (1998)

[文献書誌] S.Watanabe,T.Arai,H.Sasai,M.Bougauchi and M.Shibasaki: "The First Catalytic Enatioselective Synthesis of cis-Epoxyketones from cis-Enones" J.Org.Chem.63. 8090-8091 (1998)

[文献書誌] S,Y.Cho and M.Shibasaki: "The symmetric of cyclopentane derivatives by palladium-catalyzed coupling of prochiral alkylboron" Tetrahedron:Asymmetry. 9. 3751-3754 (1998)

[文献書誌] S.Yamasaki,T.Iida and M.Shibasaki: "Direct Catalytic Asymmetric Mannich-type Reaction of Unmodified Ketones Utilizing the Cooperation of an AlLibis(binaphthoxide) Complex and La(OTY), nH_2O" Tetrahedron Lett.40. 307-310 (1999)

[文献書誌] S.Honzawa,T.Mizutani and M.Shibasaki: "Synthetic Studies on (+)-Wortmannin An Asymmetric Construction of an Allylic Quaternary Carbon Center by a Heck Reaction" Tetrahedron Lett.40. 311-314 (1999)

1998 年度実績報告書

柴崎正勝東京大学, 大学院・薬学系研究科, 教授 (30112767)