Copper(II)salen catalysed, asymmetric synthesis of α,α-disubstituted amino acids

Cu(salen) complex 1 was found to be a versatile catalyst for the asymmetric alkylation of a range of enolates derived from a-amino acids, leading to alpha,alpha-disubstituted amino acids. The enantioselectivity of the process decreases as the size of the amino acid sidechain increases, but functionalized amino acids such as allylglycine and aspartic acid are substrates for the process. Benzylic bromides are found to be more enantioselective alkylating agents than propargylic bromides. As an example of the utility of this chemistry, an a-propargylic allylglycine derivative is prepared and subjected to ene-yne metathesis using Grubbs' catalyst to give a non-racemic cyclopentenyl amino acid. (C) 2003 Elsevier Ltd. All rights reserved.