Distant C-H Activation/Functionalization: A New Horizon of Selectivity Beyond Proximity

Abstract

Activation/functionalization of inert C-H bond has undergone rapid growth in last decade and provides novel retro-synthetic disconnections for the synthesis of valuable molecules. The selectivity is often achieved by the use of directing group and is mainly limited to the proximal C-H bond. Initially, meta C-H activations were based on electronic or steric control and now it can be achieved by employing nitrile-based end-on-template as the directing group. The compilation of the remote C-H activation strategy will provide the useful linkage to the scientific community. This article is focused on recent progress in remote C-H activation, mechanistic understanding, and its applications in the field of total synthesis of targeted molecules.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…In recent years, the application of nitriles as DGs has been dominated by directing functionalisation of an aromatic system meta to the DG. 270 – 273 …”

Decarboxylative Arylation of Pyridine 1‐Oxides and Anilides with Benzoic Acid via Palladium‐Catalyzed C–H Functionalization

“…During the early decades, the inert C–H bonds activation to prepare compounds with various properties was a great challenge for organic chemists But nowadays, there are many reports in the literatures about transition metals‐catalyzed C–H or C–Heteroatom activation to replace hydrogen or heteroatom with different functional groups . Transition metal catalyzed C–H activation is a powerful tool for the selective C–H functionalization using various active directing groups such as imines, amides, carbonyls, heterocycles, etc , .…”

Palladium‐Catalyzed Spirocyclization through C−H Activation and Regioselective Alkyne Insertion

“…[1] Thev ast majority of progress made in this field has relied on the use of ap reinstalled directing group that greatly improve selectivity and reactivity. [2][3][4] Thef unctionalization of C À Hb onds in an intramolecular fashion, wherein oxidative addition to acarbon-halogen bond situates the metal center in af avorable position to interact with ac hosen CÀHb ond have also been reported. [5] Despite the remarkable progress made in this field, selective functionalization remains achallenge.Inthis regard, the application of C À Hfunctionalization in adomino process has extended the versatility and applicability of the reaction since it enables the metal center to interact with remote bonds that may otherwise be unreactive.…”