Synthetic study toward 17-thiasteroids: synthesis of the 1-thiahydrinden-5-one subunit using a new annulation procedure and investigation of its reduction

The enantioselective syntheses of ketones 6 and 7 featuring the CD subunit of 17-thiasteroid are described. The key bicyclic 1-thiahydrindenone (S)-5 was assembled in three steps from Michael adduct (S)-12 via β-keto ester 15 using a one-pot sequential process involving cleavage of both the ketal group and the tert-butyl ester group, decarboxylation, and finally intramolecular aldol condensation. Hydridoalkyl cuprate-induced conjugate reduction of 1-thiahydrindenone (S)-5 and its corresponding sulfone (S)-23 gave 1-thiahydrindanones 6 and 7, respectively, which display unexpectedly the unnatural cis-ring junctions.

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