One-pot asymmetric synthesis of beta-cyanohydroxymethyl alpha-amino acid derivatives: formation of three contiguous stereogenic centers

[reaction: see text] One-pot asymmetric Mannich-hydrocyanation reactions are described. Reaction of unmodified aldehydes with N-PMP-protected alpha-imino ethyl glyoxylate in the presence of catalytic amounts of L-proline followed by the addition of Et(2)AlCN provided highly enantiomerically pure beta-cyanohydroxymethyl alpha-amino acid derivatives possessing three contiguous stereogenic centers as single diastereomers (93-99% ee). Control of reaction temperature during the cyanation step directed whether cyclization of the products to lactones occurred.