The chemistry of thujone. IX. Thujone as a chiral synthon for the synthesis of optically active steroid analogues. The vinylpicoline route

Abstract

AbstractThe thujone‐derived enone 1, upon base‐catalyzed reaction with 2‐methyl‐6‐vinylpyridine is converted to the pyridine analogue 5 (Scheme 1). Catalytic reduction of the latter to 6 generates two new centers of chirality which eventually become C(8) and C(14) in the ultimate synthetic steroid analogue 12. An X‐ray analysis of 6 establishes the structure and absolute configuration so as to determine its suitability in subsequent synthetic studies. The acetal derivative 7, via Birch reduction, hydrolysis, and internal aldol cyclization, is converted into the cyclohexenone analogue 10 (Scheme 2). This ‘one‐pot’ process affords an efficient conversion of the pyridine ring into a cyclohexenone system required for A‐ring construction of the steroid skeleton. Finally, conversion of 10, via the unsaturated diketone 11, provides the chiral steroid analogue 12.