Enantioselective Organocatalytic Amine Conjugate Addition
The first enantioselective organocatalytic amine conjugate addition has been successfully developed. The application of LUMO-lowering iminium catalysis has enabled the highly chemo- and enantioselective 1,4-addition of a rationally designed N-silyloxycarbamate nucleophile (HOMO-raised) to α,β-unsaturated aldehydes. Imidazolidinone 2•pTSA was found to catalyze the addition of various orthogonally N-protected silyloxycarbamate nucleophiles to a range of α,β-unsaturated aldehydes, affording synthetically useful β-amino aldehyde intermediates. The synthetic utility of the protocol was demonstrated in the rapid synthesis of enantioenriched β-amino acids in one operation and 1,3-amino alcohol derivatives in three operations.
© 2006 American Chemical Society. Received May 10, 2006. Publication Date (Web): June 30, 2006. Financial support was provided by the NIHGMS (R01 GM66142-01) and kind gifts from Amgen and Merck. Y.K.C. thanks the National Cancer Institute for a postdoctoral fellowship (1 F32 CA108376-01).Attached Files
Supplemental Material - ja063267ssi20060615_113955.pdf