Palladium/Xu-Phos-catalyzed enantioselective cascade Heck/remote C(sp2) –H alkylation reaction

Summary

Over the past 30 years, Heck-type difunctionalization of unactivated alkenes involving C−H bond activation has emerged as a powerful strategy for the construction of synthetically valuable spirocycles; however, the development of asymmetric version has largely lagged behind. Herein, we demonstrate a robust Heck-type difunctionalization of a broad range of unactivated alkenes enabled by the first palladium/Xu-Phos-catalyzed tandem Heck/remote C–H bond alkylation. Moreover, both enantiomers of the product can be efficiently prepared using the same enantiomer of a chiral ligand via a position of the phenyl ring-dependent enantiodivergent synthesis. The salient features of this methodology include operational simplicity, high chemo- and enantio-selectivities, and broad substrate scope. In addition, we first revealed that the C(sp²)–H activation, alkene insertion, and C−I reductive elimination steps are reversible by experiments.