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Site‐Selective C−H Arylation of Diverse Arenes Ortho to Small Alkyl Groups

Jyoti Dhankhar, Micha D. Hofer, Anthony Linden, Ilija Čorić

2022Angewandte Chemie International Edition21 citationsDOIOpen Access PDF

Abstract

Abstract Catalytic systems for direct C−H activation of arenes commonly show preference for electronically activated and sterically exposed C−H sites. Here we show that a range of functionally rich and pharmaceutically relevant arene classes can undergo site‐selective C−H arylation ortho to small alkyl substituents, preferably endocyclic methylene groups. The C−H activation is experimentally supported as being the selectivity‐determining step, while computational studies of the transition state models indicate the relevance of non‐covalent interactions between the catalyst and the methylene group of the substrate. Our results suggest that preference for C(sp 2 )−H activation next to alkyl groups could be a general selectivity mode, distinct from common steric and electronic factors.

Topics & Concepts

AlkylChemistryMedicinal chemistryStereochemistryCombinatorial chemistryOrganic chemistryCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsCatalytic Cross-Coupling Reactions