Gold-catalyzed cyclization of 2-alkynyl-N-propargylanilines provides a step-economic method for the construction of three-dimensional indolines. In this article, the M06 functional of density functional theory was employed to gain deeper insights into the reaction mechanism and the associated intriguing experimental observations. The reaction was found to first undergo Au(I)-induced cyclization to form an indole intermediate, 1,3-propargyl migration, and substitution with the substrate 2-alkynyl-N-propargylaniline (R1) to generate the intermediate product P1, an allene species. Subsequently, Au(I)-catalyzed conversion of P1 into the final product P2, an indoline compound, occurs first through direct cyclization rather than via the previously proposed four-membered carbocycle intermediate. Thereafter, water-assisted oxygen heterocycle formation and proton transfer generate the final product. The calculated activation free energies indicate that P1 formation is 5.9 times slower than P2 f

Vanadium-catalyzed deoxydehydration (DODH) reactions provide a cost-effective approach for the conversion of vicinal diols to olefin and polycyclic aromatic hydrocarbons. In this paper, density functional theory (DFT) calculations employing M06 and M06-L methods were conducted to clarify the mechanism of Vcatalyzed DODH. Three types of mechanisms generally proposed for transition-metal-catalyzed DODH, associated with the previously omitted spin crossover processes, were considered herein. As a result, a different catalytic cycle including a new olefin-formation mechanism was located, which is in contrast to the findings of a recent study. We found that the favorable mechanism involves the condensation of diols to form vanadium(V) diolate, reduction of the vanadium(V) diolate by PPh3, and spincrossover steps to form a triplet vanadium(III) diolate. Thereafter, single C−O bond cleavage occurs followed by another spin crossover to form a singlet alkylvanadium(V) intermediate. The final co

The introduction of a 4-mercaptan substituent was recently reported to be effective to improve the reactivity of C-terminal prolyl thioesters in native chemical ligation (NCL). To elucidate the origin of the high reactivity of 4-mercaptoprolyl thioesters, a theoretical study was performed on the transthioesterification of NCL herein with the aid of density functional theory (DFT) methods. The calculation results support a transthioesterification mechanism involving two stages. The first stage is the intramolecular transthioesterification of 4-mercaptoprolyl thioesters to form a bicyclic thiolactone intermediate and the second stage is the intermolecular transthioesterification of the thiolactone intermediate with N-terminal cysteine. The two stages proceed both via nucleophilic attack of the thiolate and proton-donor-assisted thiolate release. The thiolate release in the first stage is the ratedetermining step of the whole transthioesterification of 4-mercaptoprolyl thioesters. Based o

Efficient depolymerization methods are critical to the sustainable production of fuels and chemicals from biomass. Ligandcontrolled selective C(sp3)−O and Ar−C(sp3) cleavages of β-O-4 lignin model compounds were realized with vanadium catalysts under redox-neutral conditions or air atmosphere. To clarify the mechanism and the origin of selectivity, a joint theoretical and experimental study was performed herein. First, with the aid of density functional theory (DFT) calculations, an updated mechanism involving VV, VIV, and VIII complexes was discovered for the C(sp3)−O cleavage process catalyzed by the Schiff base vanadium complexes with an overall free energy barrier of 34.9 kcal/mol. Meanwhile, a detailed catalytic cycle involving novel stepwise O−O/Ar−C(sp3) cleavage was clarified for the Ar− C(sp3) cleavage process catalyzed by the bis(8-oxyquinolate) coordinated vanadium complexes, having an overall free energy barrier of 28.8 kcal/mol. Further analysis based on the energetic span

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.