The Lewis acidic B(C6F5)3 was recently demonstrated to be effective for the C−H alkylation of phenols with diazoesters. The method avoids the general hydroxyl activation in transition-metal catalysis. Ortho-selective C−H alkylation occurs regardless of potential para-selective C−H alkylation and O−H alkylation. In the present study, a theoretical calculation was carried out to elucidate the reaction mechanism and the origin of chemo- and regio-selectivity. It is found that the previously proposed B(C6F5)3/N or B(C6F5)3/C bonding-involved mechanisms are not favorable, and a more favored one involves the B(C6F5)3/CO bonding, ratedetermining N2 elimination, selectivity-determining electrophilic attack, and proton transfer steps. Meanwhile, the new mechanism is consistent with KIE and competition experiments. The facility of the mechanism is attributed to two factors. First, the B(C6F5)3/CO bonding reduces the steric hindrance during electrophilic attack. Second, the bonding forms the co

The Rh(III)-catalyzed oxidative coupling of oxime ether (S1) and cyclopropanol (S2) with Cu(II) as the oxidant features the combination of C−H activation and strained ring opening. The sequential order of C−H activation versus ring opening was investigated with the aid of density functional theory calculations. Prior ring opening due to the release of ring strain is found to be favored over the prior C−H activation. For the prior ring-opening mechanisms, the outer-sphere concerted metalation− deprotonation (CMD) mechanism in C−H bond activation is energetically favored. The outer-sphere CMD mechanism proposed in this work favors solvent effects and affords the N→Rh binding that allows a directing role of the Schiff base group. In conclusion, the reaction was suggested to undergo prior ring opening followed by C−H activation via the outer-sphere CMD mechanism.

A mechanistic study on Rh-catalyzed synthesis of stereospecific Z-enamide from salicyladehydes and isoxazoles has been performed with DFT calculations. The aldehydic CeH bond activation was found directed by anionic phenolic group rather than neutral phenolic hydroxyl, which reasonably rationalizes the reversibility of the CeH bond activation. Direct ring-opening rather than NeO oxidative addition of isoxazole, and subsequent CeC reductive elimination generate the stable tripodal intermediate that has been demonstrated by LC-MS analysis. Finally, sequential amino and phenolic protonations of the tripodal species produce the product Z-enamide. Stereospecificity of Z-enamide can be attributed to the rigid carbon-carbon double bond formed by direct ringopening of isoxazole. The rate-determining process is found to include the directing ring-opening and CeN reductive elimination with an overall barrier of 26.7 kcal/mol.

The condensation of carboxylic acids and amines mediated by silane derivatives provided a straightforward and sustainable method for amide bond formation with minimal waste. However, the detailed mechanism and structure–activity relationship of substrates, the topics that are of interest for both academic and industrial applications, were not clear. Herein, a systematic computational study was conducted to solve the two questions. We found that the two previously proposed mechanisms involving intramolecular acyl transfer or silanolate were less likely because the associated silanone intermediate and zwitterion adducts were too unstable with higher overall energy barriers. By comparison, the mechanism involving deprotonation of carboxylic acids, addition of carboxylates on silane reagents, dihydrogen formation to afford an acyloxysilane intermediate, carboxylic-acid-assisted addition of amines, and concerted proton transfer/amide formation, was found to be more favorable with overall en

Cu-catalyzed aerobic epoxidation offers cost-effective access to epoxides, a class of versatile chemical building blocks. Herein, a computational mechanistic study was performed to investigate Cu-catalyzed aerobic epoxidation of tertiary allylic alcohols and ethers. In contrast to the previously proposed solvent−O2 cascade activation and the O2-activation mechanisms, a substrate− O2−solvent cascade activation mechanism was revealed for not only high-strained substrates but also low- and nonstrained substrates tested herein. Specifically, it involves an induction period for the in situ generation of the actual catalyst, a Cu(II)- alkylperoxide complex derived from solvent 1,4-dioxane. Three substrate-activation pathways, depending on the substrate strain and the presence or absence of an allylic hydroxyl group, were found to be operative in this period. For the actual catalytic epoxidation, the mononuclear Cu(II) pathway was found to be favored over the dinuclear Cu(III)-oxo pathway and

1,4-Dicarbonyl motifs are notoriously difficult to synthesize, yet the mechanistic underpinnings of conventional electron donor– acceptor (EDA) strategies remain contentious. Here, we unambiguously resolve this debate and disprove the hydrogenbonding EDA (H-EDA) mechanism for decarboxylative acylation of activated alkenes with α-keto acids, establishing a concerted proton-coupled electron transfer (PCET) pathway as the exclusive operative mechanism. A combination of spectroscopic, electrochemical, photophysical, and computational studies provides definitive evidence against EDA/H-EDA formation and electron transfer, while DFT calculations revealed an exceptionally low activation barrier for concerted PCET (ΔG‡/ΔE‡ = 5.1–11.6 kcal mol-1), consistent with high efficiency under mild conditions. This photocatalyst- and base-free visible-light protocol enables rapid assembly of diverse 1,4-dicarbonyl compounds, with broad substrate scope, exceptional functional group compatibility, and reli

Here, an unpresented non-C1 synthon function of CO2 is reported to facilitate electrochemical defluorination. The introduction of CO2 modulates the electron distribution of the radical anion intermediate generated through one-electron reduction, thereby weakening the reduction potential and facilitating reduction and defluorination. CO2 is released subsequently via spontaneous decarboxylation to complete its promotion role. The presented results shed light on a distinctive utilization of CO2, which may stimulate interest in developing non-C1 synthon functions of CO2.

A KOtBu-mediated C2-benzylation of quinoline N-oxides with benzylboronates under mild reaction conditions has been developed. The reaction shows broad scope for both of the quinoline N-oxides and benzylboronates, especially, secondary and tertiary benzylboronates are also compatible with this reaction. DFT calculations indicate that the reaction is promoted by the nucleophilic addition of KOtBu to boronate rather than the deprotonation of benzylic C−H bond with KOtBu.

Cu-catalyzed aerobic epoxidation offers cost-effective access to epoxides, a class of versatile chemical building blocks. Herein, a computational mechanistic study was performed to investigate Cu-catalyzed aerobic epoxidation of tertiary allylic alcohols and ethers. In contrast to the previously proposed solvent−O2 cascade activation and the O2-activation mechanisms, a substrate− O2−solvent cascade activation mechanism was revealed for not only high-strained substrates but also low- and nonstrained substrates tested herein. Specifically, it involves an induction period for the in situ generation of the actual catalyst, a Cu(II)- alkylperoxide complex derived from solvent 1,4-dioxane. Three substrate-activation pathways, depending on the substrate strain and the presence or absence of an allylic hydroxyl group, were found to be operative in this period. For the actual catalytic epoxidation, the mononuclear Cu(II) pathway was found to be favored over the dinuclear Cu(III)-oxo pathway and

1,4-Dicarbonyl motifs are notoriously difficult to synthesize, yet the mechanistic underpinnings of conventional electron donor– acceptor (EDA) strategies remain contentious. Here, we unambiguously resolve this debate and disprove the hydrogenbonding EDA (H-EDA) mechanism for decarboxylative acylation of activated alkenes with α-keto acids, establishing a concerted proton-coupled electron transfer (PCET) pathway as the exclusive operative mechanism. A combination of spectroscopic, electrochemical, photophysical, and computational studies provides definitive evidence against EDA/H-EDA formation and electron transfer, while DFT calculations revealed an exceptionally low activation barrier for concerted PCET (ΔG‡/ΔE‡ = 5.1–11.6 kcal mol-1), consistent with high efficiency under mild conditions. This photocatalyst- and base-free visible-light protocol enables rapid assembly of diverse 1,4-dicarbonyl compounds, with broad substrate scope, exceptional functional group compatibility, and reli

Here, an unpresented non-C1 synthon function of CO2 is reported to facilitate electrochemical defluorination. The introduction of CO2 modulates the electron distribution of the radical anion intermediate generated through one-electron reduction, thereby weakening the reduction potential and facilitating reduction and defluorination. CO2 is released subsequently via spontaneous decarboxylation to complete its promotion role. The presented results shed light on a distinctive utilization of CO2, which may stimulate interest in developing non-C1 synthon functions of CO2.

A KOtBu-mediated C2-benzylation of quinoline N-oxides with benzylboronates under mild reaction conditions has been developed. The reaction shows broad scope for both of the quinoline N-oxides and benzylboronates, especially, secondary and tertiary benzylboronates are also compatible with this reaction. DFT calculations indicate that the reaction is promoted by the nucleophilic addition of KOtBu to boronate rather than the deprotonation of benzylic C−H bond with KOtBu.