The structure and function of oestrogens. VIII. Synthesis of 5,5, 10b-Trimethyl-cis-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol from 6-Methoxy-3,4-dihydronaphthalen-1(2H)-one

Abstract

Treatment of 2-hydroxymethylene-6-methoxy-3,4-dihydronaphthalen-1(2H)-one (13a) with p-meth-oxyphenyllead triacetate afforded 93% of 2-formyl-6-methoxy-2-(p-methoxyphenyl)-3,4-dihydro- naphthalen-1(2H)-one (14a) which upon deformylation and methylation gave 60% of 6-methoxy- 2-(p-methoxyphenyl)-2-methyl-3,4-dihydronaphthalen-1(2H)-one (17). An alternative route to the α α'-disubstituted ketone (17) by way of 6-methoxy-2-methyl-3,4-dihydronaphthalen-1(2H)-one (15) and 2-chloro-6-methoxy-2-methyl-3,4-dihydronaphthalen-1(2H)-one (16) was less efficient. Lithium aluminium hydride reduction of the ketone (17) followed by acetylation yielded 80% of 1 ξ acetoxy- 6-methoxy-2-(p-methoxyphenyl)-2-methyl-1,2,3,4-tetrahydronaphthalene (23), treatment of which with the trimethylsilyl enol ether of ethyl 2-methylpropanoate in the presence of zinc iodide afforded 71% of ethyl (1SR,2RS)-2-methyl-2-[6'-methoxy-2'-(p-methoxyphenyl)-2'-methyl-1',2 ',3',4'-tetrahydronaphthalen-yl'ξ-yl]propanoate (26a). Treatment of the ester (26a) or the corresponding acid (26b) with methanesulfonic acid yielded 68 or 82% respectively, of 2*-dimethoxy-5,5,10b-trimethyl- cis-4b,10b,11,12-tetrahydrochrysen-6(5H)-one (27a); Clemmensen reduction of this followed by demethylation with hydrobromicacidin aceticacid gave 49% of cis-5,5,10b-trimethyl-4b,5,6,10b,11,12- hexahydrochrysene-2,8-diol (7a).

The sterochemistry of the ring junction in compound (7a) was established by X-ray crystallography of the corresponding dimethyl ether (27b).