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

Article abstract of DOI:10.1016/S0040-4020(98)00810-2

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 1,6-asymmetric induction. 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 allyltrimetylsilane at -100 °C, the selectivity of acetal fission is 10:1 and that of nucleophilic attack is 12:1. This reaction is successfully applied to a total synthesis of marine antibiotics, (-)-malyngolide.