Abstract
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.
Published Version
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