Remote ortho-C-H functionalization via medium-sized cyclopalladation
Mario Martínez Mingo1, Nuria Rodríguez1,2, Ramón Gómez Arrayás1,2
1Department of Organic Chemistry, Universidad Autónoma de Madrid (UAM), Facultad de Ciencias, Cantoblanco, 28049, Madrid, Spain. n.rodriguez@uam.es.
Abstract:
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.
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