PubAg

Main content area

Analysis of the Palladium-Catalyzed (Aromatic)C–H Bond Metalation–Deprotonation Mechanism Spanning the Entire Spectrum of Arenes

Author:
Gorelsky, Serge I., Lapointe, David, Fagnou, Keith
Source:
Journal of organic chemistry 2012 v.77 no.1 pp. 658-668
ISSN:
1520-6904
Subject:
Lewis bases, aromatic hydrocarbons, catalysts, catalytic activity, chemical bonding, chemical structure, cleavage (chemistry), cross-coupling reactions, equations, guidelines, organic chemistry, palladium, thiophenes
Abstract:
A comprehensive understanding of the C–H bond cleavage step by the concerted metalation–deprotonation (CMD) pathway is important in further development of cross-coupling reactions using different catalysts. Distortion–interaction analysis of the C–H bond cleavage over a wide range of (hetero)aromatics has been performed in an attempt to quantify the various contributions to the CMD transition state (TS). The (hetero)aromatics evaluated were divided in different categories to allow an easier understanding of their reactivity and to quantify activation characteristics of different arene substituents. The CMD pathway to the C–H bond cleavage for different classes of arenes is also presented, including the formation of pre-CMD intermediates and the analysis of bonding interactions in TS structures. The effects of remote C2 substituents on the reactivity of thiophenes were evaluated computationally and were corroborated experimentally with competition studies. We show that nucleophilicity of thiophenes, evaluated by Hammett σₚ parameters, correlates with each of the distortion–interaction parameters. In the final part of this manuscript, we set the initial equations that can assist in the development of predictive guidelines for the functionalization of C–H bonds catalyzed by transition metal catalysts.
Agid:
5498706