Pd-catalyzed regioselective activation of C(sp2)–H and C(sp3)–H bonds

Differentiating between two highly similar C–H bonds in a given molecule remains a fundamental challenge in synthetic organic chemistry. Directing group assisted strategies for the functionalisation of proximal C–H bonds has been known for the last few decades. However, distal C–H bond functionalisation is strenuous and requires distinctly specialised techniques. In this review, we summarise the advancement in Pd-catalysed distal C(sp²)–H and C(sp³)–H bond activation through various redox manifolds including Pd(0)/Pd(II), Pd(II)/Pd(IV) and Pd(II)/Pd(0). Distal C–H functionalisation, where a Pd-catalyst is directly involved in the C–H activation step, either through assistance of an external directing group or directed by an inherent functionality or functional group incorporated at the site of the Pd–C bond is covered. The purpose of this review is to portray the current state of art in Pd-catalysed distal C(sp²)–H and C(sp³)–H functionalisation reactions, their mechanism and application in the late-stage functionalisation of medicinal compounds along with highlighting its limitations, thus leaving the field open for further synthetic adjustment.