A formal total synthesis of (±)-herbertene

Abstract

Methylation of the α,β-unsaturated ketone (2) in presence of lithium di-isopropylamide and hexamethylphosphoramide complex yielded the methylated ketone (3). Reduction of ketone (3) with sodium borohydride yielded the alcohol (4) whose tosyl derivative (5) on heating with dimethylformamide and lithium bromide afforded the diene (18). Oxidation of (18) with chromic acid produced the dienone (19) and the alcohol (23). Treatment of the dienone (19) with TosMIC (tosylmethyl isocyanide) and potassium t-butoxide yielded the nitrite derivative (20) which on reduction with di-isobutylaluminium hydride (DIBAL) followed by further reduction with sodium borohydride adsorbed on alumina yielded the alcohol (22). Oxidation of theα,β-unsaturated ketone (2) with dichlorodicyanobenzoquinone in dioxane afforded the dienone (15) which on hydrocyanation afforded principally the nitrite derivative (6) which was converted into the alcohol (22) by a seven-step sequence (reduction, oxidation, tetrahydropyranylation, methylation, reduction, tosylation, and detosylation).