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

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 σ(p) 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.

A potential role of a substrate as a base for the deprotonation pathway in Rh-catalysed C–H amination of heteroarenes: DFT insights

“…1). A base-assisted deprotonation step (here, the base is 2pb) is modelled for the cyclometallation (rhodacycle formation), in which a second substrate (basic) molecule acts as a base to abstract the proton; this step is similar to the CMD mechanism reported by Fagnou [18][19][20] (or the AMLA mechanism reported by Macgregor 16,17 ) in which deprotonation occurs from a coordinated ligand (e.g., CH3COO…”

Modulation of Benzene or Naphthalene Binding to Palladium Cluster Sites by the Backside‐Ligand Effect

“…[5,6] The lack of solution-stable benzene-Pd complexes would have raised a question on the involvement of benzene-Pd p-adducts in Pd-catalyzed benzene transformations. [7] The m 3 -benzene coordination to molecular Pd clusters is unprecedented, while the potential ability of Pd clusters to bind benzene may be indicated by the Pd surface chemistry; that is, it has been proposed that adsorbed benzene on Pd surface adopts m 3 -or m 4 -bridging coordination modes. [8] Our laboratory recently addressed the arene binding ability of Pd 3 clusters, [9] and disclosed that [2.2]paracyclophane, which is a distorted and intramolecularly p-stacking arene having much stronger coordinating ability than benzene, afforded the m 3 -arene Pd 3 3 ] in the presence of the cyclophane.…”

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

“…[89] It should also be mentioned that, in 2011, Gorelsky, Lapointe and Fagnou investigated experimentally and computationally the C-5 arylation of 2-substituted thioA C H T U N G T R E N N U N G phenes with aryl bromides, which were performed in DMA at 100 8C in the presence of K 2 CO 3 as the base and using a catalyst system consisting of 1 mol% the palladium complex 113 and 30 mol% pivalic acid (Scheme 52). [95] It was found that the reactivity of the examined thiophenes was not in agreement with S E Ar reactivity. Thiophenes bearing electron-withdrawing groups at C-2 resulted to be the most reactive substrates along with thiophenes containing the strong electron-donating N-pyrrolidine substituent.…”