A New Synthesis of Occidol

Abstract

Sodium borohydride reduction of 5,8-dimethyl-3,4-dihydronaphthalen-1-(2 H )-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 ).