Stereoselective, Oxidative C−C Bond Coupling of Naphthopyran Induced by DDQ: Stereocontrolled Total Synthesis of Deoxyfrenolicin

A formal total synthesis of pyranonaphthoquinone natural product deoxyfrenolicin 1 is described. The key step in the synthesis involves the use of stereoselective 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-induced C−C bond coupling of the naphthopyran 10 with allyltriphenyltin to give exclusively 1,3- trans naphthopyran derivative 23 . The naphthopyran 10 was obtained via oxa-Pictet−Spengler cyclization of substituted naphthalene 22, which was derived by regioselective benzannulation of chromium carbene complex 12 with acetylene 18 . This newly developed synthetic route employing a tandem benzannulation/oxa-Pictet−Spengler cyclization/DDQ-induced coupling strategy should also be applicable to the synthesis of other pyranonaphthoquinone natural products such as kalafungin 4 and nanaomycin 5 .