Stereoselective synthesis of a 2,2,5-trisubstituted tetrahydropyran chiron via 1,3- and 1,6-asymmetric induction:: A total synthesis of (-)-malyngolide

A new mode of synthesizing chiral 2,2,5-trisubstituted tetrahydropyran is described, in which two chiral centers are simultaneously introduced via facial and group selective nucleophilic acetal cleavage reaction of a bicyclic acetal 1, thereby accomplishing 1,3- and 16-asymmetric induct ion. It is revealed that acetal cleavage of the pro-R C-O bond and nucleophilic attack opposite the cleaved bond proceed preferentially. With TiCl4 and at lyltrimetyl silane at -100 degrees C, the selectivity of acetal fission is 10:1 and that of nucleophilic at tack is 12:1. This reaction is successfully applied to a total synthesis of marine antibiotics, (-)-malyngolide. (C) 1998 Elsevier Science Ltd. All rights reserved.