Theoretical Study of Cu Carbenoids in C-H Activation Reactions: The Interplay between Metal Back-Donation and Electrophilicity of the Carbon.

Our study is centered on the reactivity of copper(I) carbenoids in C-H activation reactions, particularly the role of the carbenoid carbon. The selective activation of inert C-H bonds, leading to the direct transformation of simple hydrocarbons into functionalized molecules, is a key area of organic chemistry research. Our theoretical density functional theory (DFT) study at the M06-2X/cc-PVTZ/LANL2DZ level provides insights into the catalytic C-H activation and alkyl insertion mechanisms using these copper(I) carbenoids. We analyze the effects of electron-donating (EDG: OH, CH, and NH) and electron-withdrawing groups (EWG: Cl, COOH, CN) on the reactivity, selectivity, and stability of copper carbenoids. Our systematic analysis using conceptual DFT (c-DFT), natural bond orbital (NBO), reaction force (RF), activation strain model (ASM), and energy decomposition analysis (EDA) reveals that the electronic nature of substituents significantly modulates the electrophilicity of the carbenoid carbon, thereby affecting the strength of the Cu-Cα bond, reaction barriers, and the type of mechanism. We identify carbenoids substituted with balanced EDG/EWG pairs as optimal candidates, providing kinetically and thermodynamically favorable pathways for the selective C-H activation via electrophilic substitution involving a σ-complex intermediate.