Applications of Olefination Reactions to Cassiol Synthesis

Abstract

Olefination reactions directed to the synthesis of cassiol from compounds 2-5 will be discussed.

Introduction

Cassiol (1), which exhibits a potent antiulcer activity, contains a functionalized cyclohexenone mo-eity with a quaternary stereogenic center at C-4 and a 2-vinyl-1,3-diol chain, which is connected at the C-3 position. Because of its structural features and pharmacological activity, a number of synthesis have been recorded [1]. Our approach toward the synthesis of 1 involves the C-1’- C-2’ double bond disconnection through a carbonyl olefination procedure [2]. This sequence allow us to explore the ole-fination reaction in two differents ways, switching the polarity of the coupling partners as shown in the following scheme.

By following approach a, a precursor of cassiol (1) was obtained in our laboratory, but unfortu-nately in an unsatisfactory low yield [3]. In order to improve the yield of the coupling reaction, com-pounds 2-5 were then selected for study.

Experimental

Compounds 2-5 were prepared according to standard methods.

Discussion

Due to lack of success in the coupling of 4-5 with 2 and 3 by using differents conditions of solvents and bases we turned our attention to approach b.Starting with compound 4, the diol 6 has been ob-tained. Treatment of 6 with mercaptobenzothiazole provided the corresponding sulfide 7. Starting with 7 and through the corresponding sulfone 8 we hope to improve the yield of the coupling product, on the basis of the recent report of Hart and Kozikowski et al [4].