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 palladium(0)-catalyzed methylene C(sp(3))-H arylation, which was performed in both racemic and enantioselective (e.r. 99 : 1) modes. Further elaboration of this common intermediate by nickel-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 by Suzuki-Miyaura coupling. These investigations led us to revise the structures of indidenes B and C.