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 alpha,beta-unsaturated aldehydes. Imidazolidinone 2*pTSA was found to catalyze the addition of various orthogonally N-protected silyloxycarbamate nucleophiles to a range of alpha,beta-unsaturated aldehydes, affording synthetically useful beta-amino aldehyde intermediates. The synthetic utility of the protocol was demonstrated in the rapid synthesis of enantioenriched beta-amino acids in one operation and 1,3-amino alcohol derivatives in three operations.
Chen
Young K
YK
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Yoshida
Masanori
M
MacMillan
David W C
DW
D000447:Aldehydes / Q000138:chemical synthesis; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure
D000447:Aldehydes; D000588:Amines