Ligand-Enabled Stereoselective Coupling of Methylene C(sp3)─H Bonds With Alkenyl Bromide via PdII/Pd0/PdII Catalysis.

Utilizing C(sp3)─H bonds as coupling partners for the formation of C(sp3)─C(sp2) bonds remains a significant challenge despite the progress in the past two decades. Notably, the previously reported coupling reactions of C(sp3)─H bonds with vinyl halides employing PdII/PdIV catalysis are highly limited in two ways: activated alkenyl halides and strong external directing groups were typically required. Here, we report stereoselective C(sp3)─C(sp2) cross-coupling of methylene C(sp3)─H bonds from aliphatic acids with alkenyl bromides via PdII/Pd0/PdII catalysis. A diverse array of readily available cyclic and acyclic aliphatic acids and various alkenyl bromides were coupled smoothly, affording a versatile method for forging C(sp3)─C(sp2) bonds. Complex acids and the alkenyl bromide coupling partners derived from natural products and pharmaceuticals are compatible, rendering this method amenable to late-stage modification. The stereoselectivity of this C(sp3)─C(sp2) coupling reaction with respect to both the sp3 carbon center and the double bond configuration is a valuable feature.