Synthesis of α-Methylene-γ-Butyrolactones

Abstract

The development of natural product synthesis is synonomous with the chemistry of unsaturated carbonyl compounds. Central to numerous steroid, terpene and alkaloid syntheses has been the construction of carbocyclic systems using the conjugated enone functional group (e.g. Robinson annelations, Michael additions and similar reactions).¹ In addition the unsaturated carbonyl group, which is often used for reductive alkylations, extended enolate alkylations and many other important synthetic operations,² has been found to be an integral part of the structure of many naturally occurring compounds. The long standing importance of conjugated olefinic carbonyl compounds has resulted in numerous synthetic studies related to the preparation or incorporation of this functional group into natural products. An interesting new phase of these studies has been generated from the recent isolation of naturally occurring sequiterpenoid α-methylene-γ-butyrolactones many of which possess cytotoxic activity.³ Many researchers have investigated the formation of α-methylene-γ-lactones in order to approach the total

synthesis of the more active members of this group of sesquiterpenes. Reviewed herein are the various techniques that have been developed to prepare these γ-lactones.