A Unified Strategy for the Stereocontrolled Construction of Structurally Unusual Sesquiterpene Lactones. Asymmetric Synthesis of Vulgarolide and Deoxocrispolide

Abstract

The bicyclic ketone (+)-17b reacts with vinylmagnesium bromide from its exo face, thus enabling exploitation of the anionic oxy-Cope rearrangement and direct alkylation of the enolate so formed with ethyl iodoacetate to provide 24 in an efficient, stereocontrolled manner. Tricyclic lactone 26b, readily produced from 24, proved to be a common precursor to both synthetic targets. The construction of vulgarolide (9) proceeded by transforming the SEM group in 26b into a mesylate for the purpose of conversion to epoxy acid 39 in advance of oxidative cleavage of the double bond. This transformation resulted in direct conversion to 9 and its epimer 42. Central to the companion synthesis of deoxocrispolide (4) was the ability of 37 to undergo the Michael addition of methoxide ion and of 54 to experience regiocontrolled dehydration to bridgehead olefin 55 in a protocol that involves the smooth translocation of bridgehead unsaturation with concomitant functionalization as an allylic alcohol.