Remote -C-H functionalization medium-sized cyclopalladation

• Published in: Chemical communications (Cambridge, England) Vol. 58; no. 13; pp. 234 - 24
• Main Authors: Mingo, Mario Martínez, Rodríguez, Nuria, Arrayás, Ramón Gómez, Carretero, Juan C
• Format: Journal Article
• Published: 10.02.2022
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/d1cc05310h

Compared to the tremendous progress made in directed ortho -C-H functionalization via five- or six-membered cyclopalladation, protocols with the ability to selectively activate more remote C-H bonds through the intermediacy of larger, less favorable, seven- or eight-membered metalacycles are particularly challenging and remain rare. However, such a strategy would provide new retrosynthetic opportunities for generating structural diversity and complexity. Intense recent research based on the use of either mono-anionic bidentate or monodentate directing groups is characterizing this approach as an increasingly viable tool for selective C-C and C-X bond-forming reactions. This short review provides an overview of these strategies with an emphasis on mechanistic details, synthetic applicability, limitations, and key challenges. Remote ortho -C-H bond activation via seven- or eight-membered metalacycles is particularly challenging and remains rare. This highlight provides an overview of recent advances using palladium catalysis, with an emphasis on mechanistic details.