METHYLATION AND HYDROXYMETHYLATION OF ALLYLIC ALCOHOLS VIA RADICAL CYCLIZATION - METHODOLOGY FOR STEREOSELECTIVE CONSTRUCTION OF AN ALIPHATIC CHAIN IN APPLICATION TO STEROL SYNTHESIS

Reductive free-radical cyclization of (bromomethyl)dimethylsilyl derivatives (6b-9b) of allylic alcohols (6a-9a) was studied to evaluate the scope of a novel method of methylation and hydroxymethylation of allylic alcohols. Treatment of (bromomethyl)dimethylsilyl derivatives of primary alcohols 6a and 7a with tri-n-butyltin hydride in the presence of azobisisobutyronitrile, followed by protiodesilylation of the respective cyclization products, gave in both cases a mixture of saturated methyl derivatives 11a and 12a in a ca. 1:1 ratio. Under analogous conditions (bromomethyl)dimethylsilyl derivatives of secondary alcohols 8a and 9a afforded the methylation products—sterols 13 and 14, respectively. Treatment of (bromomethyl)dimethylsilyl derivative of allylic alcohol 6a with tri-n-butyltin hydride and azobisisobutyronitrile, followed by oxidation (H202-KF-dimethylformamide) of the intermediate product, gave diol 21; the latter product was transformed via oxetane 22 into (20S)-25-hydroxycholesterol 26. Starting allylic alcohols 6a-9a were synthesized from α,β-unsaturated ester 15. Inversion of configuration at the double bond in 15, leading to Z isomer 18, was accomplished by means of phenylselenylation of saturated ester 16 and fragmentation of the corresponding phenylselenyl oxide. Regio- and stereoselectivity of radical cyclization is discussed. © 1990, American Chemical Society. All rights reserved.