Thorpe-Ingold Effect in Branch-Selective Alkylation of Unactivated Aryl Fluorides

Matthew J O'Neill; Tim Riesebeck; Josep Cornella

doi:10.1002/anie.201804479

Thorpe-Ingold Effect in Branch-Selective Alkylation of Unactivated Aryl Fluorides

Angew Chem Int Ed Engl. 2018 Jul 16;57(29):9103-9107. doi: 10.1002/anie.201804479. Epub 2018 Jun 19.

Authors

Matthew J O'Neill¹, Tim Riesebeck¹, Josep Cornella¹

Affiliation

¹ Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany.

PMID: 29786926
DOI: 10.1002/anie.201804479

Abstract

Presented herein is a general protocol for the alkylation of simple aryl fluorides with unbiased secondary Grignard reagents by means of nickel catalysis. This study revealed a general Thorpe-Ingold effect in the ligand backbone which confers a high degree of selectivity for the secondary carbon center in the C-C coupling event. This protocol is characterized by mild reaction conditions, robustness, and simplicity. Both electron-rich and electron-deficient aryl fluorides are suitable candidates in this transformation. Equally amenable are a variety of heterocycles, permitting the coupling without over alkylation at the electrophilic sites.

Keywords: C−F activation; cross-coupling; heterocycles; isomerization; nickel.