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(sp3)−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. The indane polyketides indidenes A and C were synthesized from a common intermediate through nickel‐catalyzed dehydrogenative coupling and Suzuki–Miyaura coupling, respectively. The common diol intermediate was obtained by palladium‐catalyzed methylene C−H arylation, which was performed in both racemic and enantioselective modes. This study led to the revision of the absolute configuration of indidene C.