Two-Stage Syntheses of Clionastatins A and B

A concise and divergent synthesis of the polychlorinated marine steroids clionastatin A and B from inexpensivetestosterone has been achieved through a unique two-stage chlorination-oxidation strategy. Key features of the two-stage synthesisinclude (1) conformationally controlled, highly stereoselective dichlorination at C1 and C2 and C4-OH-directed C19 oxygenationfollowed by a challenging neopentyl chlorination to install three chlorine atoms; (2) desaturation through one-pot photochemicaldibromination-reductive debromination and anti-Markovnikov olefin oxidation by photoredox-metal dual catalysis to enhance theoxidation level of the backbone; and (3) Wharton transposition to furnish the D-ring enone. This synthesis proved that theintroduction of the C19 chloride in the early stage of the synthesis secured the stability of the backbone against susceptibility toaromatization during the oxidation stage