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

Abstract

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 (σ 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 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.

Ambiphilic Al−Cu Bonding

“… [16–24] None of these species, however, has been identified as a source of nucleophilic copper. Indeed, this prospect has been explicitly excluded by DFT analysis of both the deoxygenative reactivity shown in Scheme 2 and related Cu/B addition to carbonyl‐ and imine‐containing small molecules [25–28] …”

“…Indeed, this prospect has been explicitly excluded by DFT analysis of both the deoxygenative reactivity shown in Scheme 2 and related Cu/ B addition to carbonyl-and imine-containing small molecules. [25][26][27][28] Heavier group 13 species featuring unsupported Cu À M bonding are limited to three compounds containing direct copper-aluminium interactions and several reports of copper gallyl complexes. [29][30][31][32][33] [31,32] More recently, Power and co-workers have described [{( Mes BDI)Cu- Al( Dipp BDI)}] (X, Scheme 2, Mes BDI = N,N'-bis(2,4,6-trimethylphenyl)pentane-2,4-diiminate; Dipp BDI = N,N'-bis(2,6-diisopropylphenyl)pentane-2,4-diiminate), which features a terminal Cu À Al bond.…”

Stereodivergent Nucleophilic Additions to Racemic β-Oxo Acid Derivatives: Fast Addition Outcompetes Stereoconvergence in the Archetypal Configurationally Unstable Electrophile

“…Para -electron donating substituents such as substrate 3v gave the desired product in good yield as a 1:1.2 mixture of diastereomers, although it was necessary to increase the catalyst loading to achieve full conversion. We believe the lower reactivity observed for 3v can be rationalized by the poor electrophilicity of the styrenyl electrophile and destabilization of the benzylic copper intermediate by electron-rich arenes …”

“…To distinguish between these two possibilities, chirality was use as a probe. 16 The synthesis of trifluoromethylphenyl ketone (R)-3c allowed us to track changes in the stereoisomeric composition of the starting material and products in situ using 1 H and 19 F NMR spectroscopy (Scheme 6). (−)-Menthol was incorporated into the substrate design to allow spectroscopic differentiation of intermediates.…”

From Simple Alkenes and CO2 to Fluorinated Carboxylic Acids: Computational Studies and Predictions

“…In recent years, different metal‐catalyzed systems have been reported to introduce CO 2 onto organic substrates, [28–31] often on multiple C−C bonds [32–34] . One of these systems, reported by Skrydstrup and Nielsen, [35] was originally devised for hydroboration/carboxylation of disubstituted alkenes and terminal alkynes but could serve as well for the obtention of fluorinated species relevant to biological and medical applications.…”