Ligand‐Enabled Stereoselective Coupling of Methylene C(sp ³ )─H Bonds With Alkenyl Bromide via Pd ^II /Pd ⁰ /Pd ^II Catalysis

Abstract

ABSTRACT Utilizing C(sp 3 )─H bonds as coupling partners for the formation of C(sp 3 )─C(sp 2 ) bonds remains a significant challenge despite the progress in the past two decades. Notably, the previously reported coupling reactions of C(sp 3 )─H bonds with vinyl halides employing Pd II /Pd IV catalysis are highly limited in two ways: activated alkenyl halides and strong external directing groups were typically required. Here, we report stereoselective C(sp 3 )─C(sp 2 ) cross‐coupling of methylene C(sp 3 )─H bonds from aliphatic acids with alkenyl bromides via Pd II /Pd 0 /Pd II 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(sp 3 )─C(sp 2 ) 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(sp 3 )─C(sp 2 ) coupling reaction with respect to both the sp 3 carbon center and the double bond configuration is a valuable feature.