Progress toward a Convergent, Asymmetric Synthesis of Jervine.

Abstract

Progress toward a convergent approach for the enantioselective synthesis of the Veratrum alkaloid jervine is presented. The two requisite fragments were stereoselectively and efficiently fashioned from economical and readily available reagents. Key reactions include (a) a highly diastereoselective Ireland-Claisen rearrangement to establish the necessary cis-relationship between the amine and methyl group on the tetrahydrofuran E-ring; (b) a diastereoselective selenoetherification reaction that enabled the assembly of the D/E oxaspiro[4.5]decene in the needed configuration; and (c) an enzymatic desymmetrization of an abundant achiral diol en route to a key four-carbon building block as a practical alternative to a protected Roche ester reduction.