Methylene C(sp3)-H Arylation Enables the Stereoselective Synthesis and Structure Revision of Indidene Natural Products.

The divergent synthesis of two indane polyketides of the indidene family, namely (±)-indidene A (11 steps, 1.7%) and (+)-indidene C (13 steps, 1.3%), is reported. The synthesis of the trans-configured common indane intermediate was enabled by Pd0-catalyzed methylene C(sp3)-H arylation, which was performed in both racemic and enantioselective (e.r. >99:1) modes. Further elaboration of this common intermediate by Ni-catalyzed dehydrogenative coupling allowed the rapid installation of the aroyl moiety of (±)-indidene A. In parallel, the biphenyl system of (±)- and (+)-indidene C was constructed via Suzuki-Miyaura coupling. These investigations led us to revise the structures of indidenes B and C.