The Role of 1,2-Palladium Migration/Insertion on C(sp3)-H Functionalization.

Abstract

Selective functionalization of C-(sp³)-H bonds remains challenging yet crucial for researchers. A frequently used approach by chemists to tackle this challenge involves leveraging 1,2-metal migration/insertion, which enables the selective activation and cleavage of a specific C-(sp³)-H bond adjacent to or distant from the directing group. Palladium is among the most commonly employed catalysts for C-(sp³)-H functionalization through metal migration/insertion, with Pd-(OAc)₂ being the predominant palladium complex utilized in these processes. 1,2-Palladium migration is a key strategy for achieving selective C-(sp³)-H functionalization. After palladium coordinates to a directing group, its migration can activate the nearby C-(sp³)-H bond. With subsequent migrations, more distant C-(sp³)-H bonds can be targeted and transformed into C-(sp³)-functional groups. During the 1,2-insertion of palladium, the migration of palladium takes place following the activation of the C-(sp³)-H bond. This migration step typically involves the palladium inserting into a double bond, which links the C-(sp³)-H bond to a C-(sp²)-H bond, thereby progressing the reaction. Ultimately, this review highlights that C-(sp³)-H functionalization via 1,2-palladium migration/insertion has the potential to selectively modify both proximal and remote C-H bonds in organic molecules, offering a valuable tool for researchers to synthesize a wide range of organic compounds in future studies. This account encompasses all types of 1,2-palladium migration/insertion and examines their impact on C-(sp³)-H functionalization. It provides a detailed analysis of the mechanisms involved and explores how these migrations enable the activation of both remote and proximal C-(sp³)-H bonds with the directing group.