One-pot asymmetric synthesis of β-cyanohydroxymethyl α-amino acid derivatives:: Formation of three contiguous stereogenic centers

[GRAPHICS] One-pot asymmetric Mannich-hydrocyanation reactions are described. Reaction of unmodified aldehydes with MPMP-protected alpha-imino ethyl glyoxylate in the presence of catalytic amounts of L-proline followed by the addition of Et2AlCN 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.