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 Cu-I-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 H-1 NMR time course studies and subsequent Hammett analysis (sigma(p)) of carbon dioxide addition to (beta-borylbenzyl)copper(I) complexes (benzyl = CH2Arp-X ) revealed a linear correlation with a negative rho (rho) 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-CFr3 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 (beta-borylbenzyl)copper(I) yields a metastable intermediate that precedes an S-E-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.

Automated summary

An experimental and computational study was conducted on the carboxylation of vinyl arenes catalyzed by copper(I), revealing different reaction rates under various substitution conditions and the impact of the additive PPh3 on the carboxylation pathway. The study also demonstrated the existence of a metastable intermediate prior to the S-E-carboxylation mechanism, which is kinetically favorable for electron-deficient benzyl-copper species. This research highlights the kinetic complexities and multiple pathways involved in copper-based carboxylation chemistry.