Approaches to the total synthesis of vernolepin

Abstract

The basic goal of this study was the development of an efficient approach to the total synthesis of vernolepin. Special attention was paid to the development of an efficient synthesis of bicycle[4.3.1]-dec-3-en-9,10-diones 9 and the synthesis of various 4-alkoxycrotonates. [Figure1] The reaction of the morpholine enamine of 4-cycloheptenone with 4-allyloxycrotonyl chloride produced dione 46. Dione 46 was readily converted to enone 72 by treatment with phenyltrimethylammonium tribromide followed by dehydrohalogenation utilizing N,N-dimethylformamide, lithium carbonate and lithium bromide. Enone 72 was converted to enone 73 by treatment with ethylene glycol, benzene and a trace of p-toluenesulfonic acid. Enone 73 was readily converted to adduct 76, which is a bisnorvernolepin synthon, by utilization of a divinyl cuprate. [Figure2]