Asymmetric conjugate addition / a,P-Unsaturated esters / Homochiral amidocuprates / P-Amino acids / a-Deuterio p-amino acids Conjugate addition of homochiral amidocuprates based on N-[(R)-1-phenylethyl]trimethylsilylamine or bis[(R)-1-phenylethyllamine to a,p-unsaturated esters provides an efficient methodology for t h e asymmetric synthesis of p-amino acids. Trapping of t h e intermediate enolate with D 2 0 yields a-deuterated p-amino acids with excellent stereoselectivity. Homochiral p-amino acids have become a major target in preparative chemistry [']. They often serve as precursors for p-lactam antibioticd2]], peptidomimeticd3I or various other compounds of biological intere~t[~.~1. For instance, the N-benzoyl-3-phenylisoserine side chain at C-13 of taxol is responsible for its biological ac-tivityL61.
Methods for the preparation of p-amino acids rely on functional group transformation of chiral pool compounds, addition reactions of enolates bonded to homochiral auxiliaries with imines or addition reactions of nitrogen nucleophiles with homochiral a,p-unsaturated esters. One approach, reported to proceed with excellent stereoselectivity, is the Michael addition of homochiral lithium amides or magnesium amides to a,P-unsaturated ester^[^-"].
However, homochiral amidocuprates have not been applied to achieve this type of transformation. Achiral amidocuprates are known to be highly efficient reagents for the diastereoselective synthesis of p-lactams via a reaction sequence consisting of conjugate addition/aldol condensation/P-lactam formation[141.
The Michael addition of lower order amidocuprates derived from N-[(R)-I-phenylethyl]trimethylsilylamine (1) or bis[(R)-Iphenylethyllamine (4)[151 to a,P-unsaturated ethyl esters proceeds stereoselectively to give the corresponding p-amino acid esters 3 or 5 (e. g. derivatives of P-aminobutyric acid, P-phenylalanine. ptyrosine, and p-leucine).