Catalytic Asymmetric Alkylation and Protonation of Lithium Enolates

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12470478
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: KOGA Kenji Nara Institute of Science and Technology, Research & Eduction Center for Materials Science, Professor, 物質科学教育研究センター, 教授 (10012600)
• Co-Investigator(Kenkyū-buntansha): SHIRAI Ryu-ichi Nara Institute of Science and Technology, Research & Education Center for Materials Science, Associate Professor, 物質科学教育研究センター, 助教授 (80183838)
• Project Period (FY): 2000 – 2002
• Keywords: Catalytic Asymmetric Deprotonation / Catalytic Asymmetric Alkylation / Catalytic Asymmetric Protonation / Tetradentate Chiral Amine / Bidentate Achiral Amine

Research Abstract

Enolates are prepared by deprotonation of carbonyl compounds, and are important intermediates in organic synthesis to give a variety of products by the reactions with various electro-philes. The purpose of the present study is to design and synthesize various mutidentate chiral amines, and to devise methods to carry out efficiently enantioselective asymmeric alkylation and protonation rectons of achiral lithium enolates using these chiral multidentate amines as chiral auxiliries. The final object of the present research is to make these reactions catalytic as to the chiral amines employed.
(1) Catalytic Asymmetric Alkylation : Examinations on the enantioselective asymmetric alkylation of prochiral lithium enolates prepared by deprotonation of cyclohexanone and 1-tetralone have shown that the chemical yields of the reactions are highly dependent on the coordination numbers of the chiral multidentate amines examined, lower by using bidentate amines, while very high by using tetradentate chiral amines. Based on this finding, catalytic asymmetric alkylation reaction was realized by using 0.05 equivalent of a tetradentate chiral amine in the presence of 2 equivalents of a bidentate achiral amine.
(2) Catalytic Asymmetric Protonation : Proton is an electrophile, and protonation reaction of lithium enolates is known to be a very fast reaction. To realize catalytic asymmetric protonation of prochiral lithium enolates, examinations were made to protonate the lithium enolates slowly by adding proton source to the reaction mixture very slowly. It is now shown that catalytic asymmetric protoantion of prochiral lithium enolates can be carried out efficiently by the reaction conditions similar to those described above for catalytic asymmetric alkylation.