High Substrate/Catalyst Organocatalysis by a Chiral Brønsted Acid for an Enantioselective Aza-Ene-Type Reaction
Masahiro Terada*, Kyoko Machioka, Keiichi Sorimachi
*Department of Chemistry, Graduate School of Science, Tohoku University,
Aramaki, Aoba-ku, Sendai 980-8578, Japan, Email: mteradamail.tains.tohoku.ac.jp
M. Terada, K. Machioka, K. Sorimachi, Angew. Chem. Int. Ed., 2006, 45, 2254-2257.
DOI: 10.1002/anie.200503477
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Abstract
A highly efficient enantioselective aza-ene-type reaction of N-benzoylimines with enecarbamates has been developed. The reaction can be performed at extremely low loading of a chiral Brønsted acid catalyst without notable loss in enantioselectivity.
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proposed mechanism
Details
This document discusses the development of a highly efficient enantioselective aza-ene-type reaction catalyzed by a chiral Brønsted acid, specifically a binaphthol-derived monophosphoric acid. The research, conducted by Masahiro Terada, Kyoko Machioka, and Keiichi Sorimachi, addresses the challenge of achieving high catalytic efficiency in organocatalysis. The study demonstrates that the reaction of N-benzoylimines with enamides or enecarbamates can be performed with high substrate-to-catalyst (S/C) ratios, up to 2000:1, without significant loss of enantioselectivity. The optimal conditions were found using toluene as the solvent, yielding high enantioselectivity and efficiency. The reaction mechanism involves dual hydrogen-bonding interactions facilitated by the phosphoric acid catalyst. The research also explores the reaction's applicability to various N-benzoylimines, achieving excellent yields and enantioselectivities. Additionally, the study highlights the practical utility of the method through large-scale experiments and the synthesis of C2-symmetric 1,3-diamine derivatives, which are valuable in pharmaceuticals and as chiral ligands. The findings offer a practical route to synthetically useful β-amino-imine derivatives and demonstrate the potential for further development in high S/C organocatalysis.
Key Words
asymmetric synthesis, Brønsted acids, ene reaction, organocatalysis, phosphoric acid, β-amino ketones
ID: J06-Y2006-900