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

The 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 .