Experimental and Computational Analysis of CO2 Addition Reactions Relevant to Copper-Catalyzed Boracarboxylation of Vinyl Arenes: Evidence for a Phosphine-Promoted Mechanism

An experimental and computational mechanistic investigation of the key carboxylation step in copper­(I)-catalyzed boracarboxylation of vinyl arenes is presented here. Catalytically relevant intermediates, including a series of CuI-spiroboralactonate complexes with electronically differentiated vinyl arenes and stabilized by the N-heterocyclic carbene (NHC) ligand IPr (IPr = 1,3-bis­(2,6-diisopropylphenyl)­imidazol-2-ylidine), were isolated and characterized. In situ 1H NMR time course studies and subsequent Hammett analysis (σp) of carbon dioxide addition to (β-borylbenzyl)­copper­(I) complexes (benzyl = CH2Arp‑X) revealed a linear correlation with a negative rho (ρ) value. Density functional theory (DFT) calculations support a direct CO2 insertion as the primary mechanism for electron-rich benzyl–copper carboxylation. Kinetically sluggish carboxylation of the electron-poor trifluoromethyl-substituted benzyl–copper complex (benzyl = CH2Arp‑CF3) was accelerated upon the addition of exogenous triphenylphosphine (PPh3). Conversely, the additive inhibited the reactions of the electron-rich tert-butyl-substituted benzyl–copper complex (benzyl = CH2Arp‑tBu). These kinetic observations implied that a second carboxylation pathway was likely operative. DFT analysis demonstrated that prior binding of the electron-rich phosphine additive at (β-borylbenzyl)­copper­(I) yields a metastable intermediate that precedes an SE-carboxylation mechanism, which is kinetically favorable for electron-deficient benzyl–copper species and circumvents the kinetically challenging direct insertion mechanism. The mechanistic picture that emerges from this complementary experimental/computational study highlights the kinetic complexities and multiple pathways involved in copper-based carboxylation chemistry.