Steroids: Ix. The Solvolysis of 4,4-Diethylcholesteryl Methanesulfonate

Abstract

The acetol~sis of 4,4-diethylcholesteryl mesylate gave 11% 3,4-dialkyl (A), 39% 3a,5-cyclo (C), and 50% A-norcholestene (B) derivatives. The corresponding yield for the 4-4,dimethyl series is 25, < 11.6, and > 61.4%.Knowledge of the mechanism of solvolysis of cholesteryl derivatives does not permit one to predict with reasonable accuracy the solvolytic reactions of 4-monomethyl (2, 3) or 4,4-dimethyl (4, 5, 6) cholesteryl derivatives. Since small changes in structure seem to have a fairly large effect on the reactions, we undertook a study of the reactions of 4,4-diethylcholesteryl mesylate, expecting to obtain a product distribution similar to that observed in the solvolysis of 4,4-dimethylcholesteryl tosylate. In that reaction (6), one isolates products fornlally derived from carbonium ions A, B, and C in the yields indicated.Since the results obtained are somewhat unexpected, me would like to report on them.Cholest-4-en-3-one (7) was converted to 4,4-diethylcholest-5-en-3-one (11) by appropriately modifying the procedure described by Woodward, Barton, and co-workers (8). Lithium aluminium hydride reduction (8) of ketone I1 gave 4,4-diethylcholesterol (111) in quantitative yield. When ketone I1 \vas reduced with sodium borohydride in N,Ndimethylformamide (9) and the resulting inixture separated on alumina, there was obtained the starting material, 3a-alcohol IV, and 3p-alcohol I11 in 63.5, 1.2, and 15.1% yields respectively. The stereochemical assignment of the two epiineric alcohols was based on the relative yield of products obtained and the relative ease of elution on alumina (10).