Toward the development of a general chiral auxiliary. Enantioselective alkylation and a new catalytic asymmetric addition of silyloxyfurans: application to a total synthesis of (-)-rasfonin.

ABSTRACT

An enantioselective total synthesis of the apoptosis-inducing natural product, (-)-rasfonin, is described. Camphor lactam-mediated asymmetric alkylation reactions enabled the installation of three stereogenic centers with >955 diastereoselectivity. A modified Corey-Peterson olefination was employed in the construction of the (E,E)-diene system. A highly diastereoselective, asymmetric vinylogous Mukaiyama aldol addition was conducted using a chiral cationic oxazaborolidine catalyst. The pyranone core of the natural product was prepared via a DBU-promoted rearrangement of a furanol to its corresponding pyranol with concomitant [1,4]-silyl transfer.