Quassinoid Synthesis. 2. Preparation of a Tetracyclic Intermediate Having the Bruceantin Tetrahydrofuran Ring

Article abstract of DOI:10.1021/jo00385a008

A synthetic approach to the quassinoid compound bruceantin is described.Tricyclic acid 5, prepared from 2-(methoxycarbonyl)cyclohexanone in one step by the method of Fuchs, is converted into ketal lactone 6 and thence into diol 7.The primary hydroxyl may be selectively protected to give any of several derivatives, including the tetrahydropyranyl derivative 10.Allylic oxidation of this substance provides enone 13, which is dehydrated by treatment with 4-(dimethylamino)pyridine in refluxing acetic anhydride to obtain 16.Lithium/ammonia reduction of 16 yields saturated ketone 23, which is carboxylated by the Stiles procedure to obtain the enolic β- keto ester 26.This material is dehydrogenated to 28 by a novel procedure wherein the enol is heated with thionyl chloride and collidine in refluxing carbon tetrachloride.It is proposed that the dehydrogenation occurs by sulfenylation on carbon, followed by pyrolytic elimination of the resulting sulfenyl chloride ( Scheme III ).The elements of the eventual tetrahydropyranone ring are introduced at this stage by reaction of 28 with silyl ketene acetal 29 at high pressure.The product, enol silane 31, is deprotected by treatment with pyridinium p-toluenesulfonate in warm ethanol to obtain 39.Bromocyclization of this material upon treatment with N-bromosuccinimide in tetrahydrofuran affords bromo eter 40, which rearranges to tetrahydrofuran 41 upon being heated at reflux in N,N-dimethylformamide solution.Deprotection of the latter material provides the β-keto ester 42, a viable intermediate for a bruceantin synthesis.