Computational Explorations of Mechanisms and Ligand-Directed Selectivities of Copper-Catalyzed Ullmann-Type Reactions

Abstract

Computational investigations of ligand-directed selectivities in Ullmann-type coupling reactions of methanol and methylamine with iodobenzene by β-diketone-and 1,10-phenanthroline-ligated Cu(I) complexes are reported. Density functional theory (DFT) calculations with several functionals were performed on both the nucleophile formation and aryl halide activation steps of these reactions. The origin of ligand-directed selectivities in N-vs. O-arylation reactions as described in a previous publication (J. Am. Chem. Soc. 2007, 129, 3490-3491) were studied and explained. The selectivities observed experimentally are not derived from initial Cu(I)-nucleophile formation, but from the subsequent steps involving aryl halide activation. The arylation may occur via single-electron transfer (SET) or iodine atom transfer (IAT), depending on the electrondonating ability of the ligand and nucleophile. Mechanisms involving either oxidative addition/ reductive elimination or sigma-bond metathesis are disfavored. SET mechanisms are favored in reactions promoted by the β-diketone ligand; N-arylation is predicted to be favored in these cases, in agreement with experimental results. The phenanthroline ligand promotes O-arylation reactions via IAT mechanisms in preference to N-arylation reactions, which occur via SET mechanisms; this result is also in agreement with experimental results.

Understanding the Heteroatom Effect on the Ullmann Copper-Catalyzed Cross-Coupling of X-Arylation (X = NH, O, S) Mechanism

“…The Gibbs free energy required to transfer the electron from the cooper complexes to the iodobenzene is significantly high, i.e., +107.0, +118.1, and +120.2 kcal/mol for 2-NH, 2-O and 2-S, respectively. The Gibbs energy barriers of this process were estimated using the Marcus-Hush theory [70][71][72][73][74][75][76][77] within the Saveant's model [78][79][80] for the SET coupled with the cleavage of the Ph-I bond (see the Supplementary Materials pages S2-S4 for details) [51]. The activation barriers obtained are +116.0, +131.9, and +135.1 kcal/mol for 2-NH, 2-O, and 2-S, respectively.…”

“…The studies carried out on the reactivity of these complexes, including kinetic studies and radical clock experiments, argued against pathways involving radical intermediates. Conversely, Buchwald and Houk by experimental and computational methods claimed that the SET and HAT mechanisms are energetically more favorable for Ullmann N-and O-arylation of alkyl amines and alcohols with aryl iodides [51]. Further support to these one-electron mechanisms was given by a number of detailed theoretical studies on the N-, O-, and S-arylation reported by Zhang and co-workers [57][58][59][60][61].…”

“…The four most invoked reaction mechanisms of Ullman-type reactions. Single Electron Transfer (SET), Halogen Atom Transfer (HAT), Oxidative Addition-Reductive Elimination (OA-RE) and σ-bond Metathesis (MET) [51].…”

Antagonistic Effect of Acetates in C–N Bond Formation with In Situ Generated Diazonium Salts: A Combined Theoretical and Experimental Study

“…[61] This type of theoretical level has proven its accuracy in the mechanistic investigations of copper-catalyzed C-N bond-forming reactions. [8,[62][63][64][65] The heats of formation of complexes with various numbers of ligands and various conformations were theoretically evaluated (see Table 2). We assumed to start that a neutral Cu I complex is formed (complexes I-V).…”

Current Applications of Computational Chemistry in JACS—Molecules, Mechanisms, and Materials

“…2 Buchwald, Houk, and co-workers investigate computationally the reason for the dependence on catalyst structure of the regioselectivity of N versus O in Ullmann-type reactions and provide a convincing rationalization. 3 Caflisch and co-workers report the results of molecular dynamics (MD) simulations which find that amyloid polymorphism is under kinetic rather than thermodynamic control. 4 On the basis of the results of another type of MD simulation, semiclassical trajectory calculations, Carpenter, Glowacki, and Goldman make a bold prediction about the ring-opening of bicyclo[2.1.0]-pentene.…”