The Role of 1,2-Palladium Migration/Insertion on C(Sp3)–H Functionalization Publisher



Karimtabar MS ; Mohammadkhani Y ; Mahdavic M ; Rashidi Ranjbar P
Source: ACS Organic and Inorganic Au Published:2025

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)2being 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. © 2025 Elsevier B.V., All rights reserved.