A New Synthesis of Occidol

Abstract

Sodium borohydride reduction of 5,8-dimethyl-3,4-dihydronaphthalen-1-(2H)-one (4) yielded 5,8-dimethyl-1,2,3,4-tetrahydro-1-naphthol (5). The tetralol 5 on Vilsmeier-Haack reaction with N,N-dimethylacetamide yielded 1-(5,8-dimethyl-3,4-dihydro-2-naphthyl)ethan-1-one (7) which on hydrogenation over Pd/C afforded 1-(5,8-dimethyl-1,2,3,4-tetrahydro-2-naphthyl)ethan-1-one (8). The tetralol 5 on Vilsmeier-Haack formylation gave 5,8-dimethyl-3,4-dihydro-2-naphthaldehyde (9) which on reduction with lithium aluminium hydride followed by oxidation with the Jones reagent furnished 5,8-dimethyl-1,2,3,4-tetrahydro-2-naphthoic acid (11). The acid 11 on treatment with excess of methyllithium yielded (±)-occidol (1); with two moles of methyllithium it yielded ketone 8, which on reaction with methyllithium furnished (±)-occidol (1).