A New Total Synthesis of Bulnesol

Abstract

Some years ago we began work on a general hydroazulenic sesquiterpene synthesis based on the known photo-ene product (II) of citral (I).¹ The projected key step, the cyclization of an olefinic aldehyde, has been extensively studied in model systems: the stereochemical outcome, and other data, suggest a concerted electrocyclic mechanism with the carbonyl serving as an enophile.² However application of this reaction to model aldehydes yielding the guaiane skeleton were less encouraging. Aldehyde III (R[dbnd]H), obtained from photocitral-A by two successive homologations using cyanide displacement of tosylate, gave at best a 60% yield of cyclized material—a mixture of olefin isomers and hydroxy epimers. Initial attempts to incorporate a group R suitable for later elaboration into the isopropylol side chain common in guaianes were also discouraging.