Tandem Carbon-Radical Peroxidation−Addition to Carbonyl Groups Reaction. A New Synthesis of Steroidal β-Peroxy Lactones

A mild and efficient synthesis of beta-peroxy lactones by alkoxy radical beta-fragmentation reaction of gamma-hydroxy carbonyl compounds is described. Steroidal models 5-hydroxy-4-nor-3-oxa-5 alpha-cholestan-2-one (1), 5-hydroxy-5 alpha-cholestan-2-one (2), and 5,17 beta-dihydroxy-4-nor-5 alpha-androstan-2-one 17-acetate (3) were synthesized to test the present methodology. These substrates are subjected to photolysis with visible light in the presence of (diacetoxyiodo)benzene, lead tetraacetate, or HgO, I-2, and molecular oxygen to generate the corresponding alkoxy radical. The fragmentation of this radical results in the carbon radical which is trapped by molecular oxygen in the key step to generate a peroxy radical. Intramolecular addition of this peroxy radical to the carbonyl group present in the molecule is followed by beta-fragmentation to yield the peroxy lactone radical. Subsequent trapping of this radical results in stable peroxy lactone. In all cases, regiospecific beta-fragmentations and stereoselective peroxidation at C-10 radical were observed. This operationally simple multistep radical procedure permitted us to synthesize steroidal beta-peroxy lactones 8, 12, and 15 in moderate to good yields.