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Tuning the Regioselectivity of Palladium-Catalyzed Direct Arylation of Azoles by Metal Coordination

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journal contribution
posted on 22.02.2016, 06:27 by Serge I. Gorelsky
Cleavage of C–H bonds of free and CuI-bound N-methylimidazole and oxazole via a concerted metalation–deprotonation (CMD) pathway was evaluated, and the distortion–interaction analysis was performed to quantify the various contributions to the CMD transition states. Metal binding to the N3 atom for these azoles imparts an increase of C–H bond acidities and, thus, enhances CMD reactivity for all C–H bonds, leading to a reliable C2 > C5 > C4 reactivity compared to a bias for C5 > C2 arylation for noncoordinated azoles. This type of substrate activation and tuning of regioselectivity by metal coordination to heteroarenes can be used for many other classes of substrates for direct arylation reactions.