Highly stereoselective synthesis of stereochemically defined polyhydroxylated propargylamines by alkynylation of n-benzylimines derived from (R)-glyceraldehyde.

Abstract

The addition of the lithium derivative of tert-butyldimethylsilyl propargyl ether to N-benzylimines derived from (R)-2,3-O-isopropylideneglyceraldehyde has been achieved with acceptable yields and high diastereoselectivities. The syn/anti diastereoselectivity of the addition reaction can be controlled and reversed by the appropriate use of Lewis acids as imine precomplexing agents. Double stereodifferentiation processes using imines derived from (R)-2,3-O-isopropylideneglyceraldehyde and (R)- or (S)--methylbenzylamine as starting materials occur with total stereocontrol to afford syn and anti vic-propargylamino alcohol derivatives with orthogonally protected hydroxymethyl groups on both sides of the central core.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)