Dimethylformamide → 1,1'-[Oxybis(methylene)]bis(4-methoxybenzene)

Participants

Reaction Steps

The starting species, Compound 2a, 4-dimethyl-5a-cholesta-8,14-dien-3b-ol, was prepared from 7-dehydrocholesterol (Sigma Chemical Co., P.O. Box 14508, St. Louis, Mo. 63178) by the method described by Bloch and Gautschi in J. Chem. Soc., 223 (6), 1343 (1958). Treatment of the 8,14-dien-3b-ol (2a) with sodium hydride (Alfa Products, P.O. Box 299, Danvers, Mass. 01923) and 4-methoxybenzyl chloride [prepared by the method described by R. L. Schriner and C. J. Hull in J. Org. Chem., 10, 228 (1945)] in 4 parts of tetrahydrofuran and 1 part of N,N-dimethylformamide at 70° C. afforded the corresponding p-methoxybenzyl ether 2b in near quantitative yield. Hydroxylation of the diene 2b with stoichiometric amount of osmium tetroxide (Alfa) in the presence of 10 equivalents of anhydrous pyridine (Aldrich Chemical Co., Inc., 940 West St., Paul Ave., Milwaukee, Wis. 53233) in benzene provided the 14,15-diol in 82% yield. Opening of the steroid D-ring was achieved by reacting the diol 3b with lead tetraacetate (Aldrich, recrystallized from acetic acid) in benzene to give the corresponding tricyclic enone-aldehyde 4b in quantitative yield. Selective conversion of the enone-aldehyde 4b to a dimethyl acetal 5b by with trimethyl orthoformate (Aldrich) and camphorsulfonic acid (Aldrich) in methanol (>95% yield) ensured the functionalization at C-14 without complication at C-15. The necessary functional groups at 14-position were introduced at this stage by adding various nucleophiles to the carbonyl. Diisobutyl aluminum hydride (Aldrich, 1 molar solution in hexane) reduction of the enone 5b in methyl chloride afforded the alcohol 12b in 85% yield.

Provenance & Evidence