A mild and efficient synthesis of β-peroxy lactones by alkoxy radical β-fragmentation reaction of γ-hydroxy carbonyl compounds is described. Steroidal models 5-hydroxy-4-nor-3-oxa-5α-cholestan-2-one (1), 5-hydroxy-5α-cholestan-2-one (2), and 5,17β-dihydroxy-4-nor-5α-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, I2, 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 β-fragmentation to yield the peroxy ladone radical. Subsequent trapping of this radical results in stable peroxy lactone. In all cases, regiospecific β-fragmentations and stereoselective peroxidation at C-10 radical were observed. This operationally simple multistep radical procedure permitted us to synthesize steroidal β-peroxy lactones 8, 12, and 15 in moderate to good yields.

This work was supported by the Investigation Programme no. PB93-0171 of the Dirección General de Investigación Científica y Técnica. A.B. thanks the Ministerio de Educación y Ciencia, Spain, for a fellowship.

9 pages, 1 table, 7 schemes.-- Supporting information available at: http://pubs.acs.org/doi/suppl/10.1021/jo00130a020