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NB_MS-SI_07152020.pdf (13.83 MB)

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

submitted on 16.07.2020 and posted on 21.07.2020 by Notashia Baughman, Novruz G. Akhmedov, Jeffrey L. Petersen, Brian Popp
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 NHC ligand IPr (IPr = 1,3-Bis(2,6-di-isopropylphenyl)-4,5-dihydroimidazol-2-ylidine), were isolated and characterized. In situ 1H NMR timecourse studies and subsequent Hammett analysis (p) 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 electron-poor trifluoromethyl-substituted benzyl-copper complex (benzyl = CH2Arp-CF3) was accelerated upon addition of exogenous PPh3. Conversely, the additive inhibited reactions of 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 meta-stable 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.


National Science Foundation CHE-1752986

National Science Foundation CHE-1228336

National Science Foundation CHE-1336071

National Science Foundation OAC-1726534


Email Address of Submitting Author


West Virginia University


United States of America

ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no competing financial interests.

Version Notes

Version 07.15.2020