Benzene ring functionalization provides useful alternatives to access indole derivatives and has received much attention in recent years. In this work, the mechanism of Pt(II)-catalyzed cyclization/alkynylation of benziodoxole with pyrrole homopropargylic ethers to generate C5-alkenylated indole derivatives has been studied with the aid of density functional theory (DFT) calculations. We found that fivemembered-ring cyclization/six-membered-ring cyclization is competitive in the formation of an indole skeleton. The following aromatization stage prefers the reaction sequence bicarbonate-assisted deprotonation at the C3a position, H2CO3-promoted methoxy elimination at the C7 position, and bicarbonate-assisted deprotonation at the C6 position. In the last alkynylation stage, the oxidative substitution mechanism assisted by H2CO3 is found to be favored over the previously proposed 1,2-iodo shift and oxidative addition. The overall ratedetermining step is oxidative substitution. Additionall

The couplings of carboxylic acids and amines promoted by dichlorosilane derivatives provide a promising tool for amide synthesis and peptide coupling, in which an unprecedented mechanism was proposed for the amide bond formation process. To investigate this mechanistic proposal and enrich the understanding of this novel reaction, a theoretical study was conducted herein. The formation and interconversion of silylamine and silyl ester intermediates were calculated to be kinetically feasible under the experiment conditions. However, the subsequent amidation via direct elimination on the AcO-Si(L)(L′)-NHMe intermediate was found to involve a high energy barrier due to the formation of an unstable silanone. By contrast, the in situ generated salts can promote the amidation process by generating a silanol as the temporary product. Similarly, the anhydride formation mechanism can proceed via direct elimination or salt-assisted elimination on the AcO-Si(L)(L′)-OAc intermediate but is less fav

The Pd-catalyzed cross-coupling of aryl iodide, benzoic anhydride and ethyl acrylate provided a useful alternative to synthesize alkenylated aryl ketones with good selectivity and functional-group tolerance. In this manuscript, density functional theory (DFT) calculations were performed to address the detailed reaction mechanism. Computational results support the experimentally proposed Pd(0)–Pd(II)–Pd(IV) catalytic cycle and further clarify that the rate-determining step is the oxidative addition of benzoic anhydride, the regioselectivity-determining step is the migratory insertion of ethyl acrylate and the following β-H elimination determines the stereoselectivity. The regioselectivity can be attributed to the steric and electronic effect of ethyl acrylate and the stereoselectivity can be explained by the steric repulsion between the toluene moiety and the CO2Et moiety. Furthermore, we found that norbornene not only acts as the removable scaffold in Catellani–Lautens type reactions,

An enamide-based 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS) method was recently disclosed for the synthesis of peptide thioesters. In this manuscript, density functional theory (DFT) calculations were performed to provide deeper mechanistic insights into this reaction. The calculation results clarified the detailed mechanisms of the relevant N-to-S acyl transfer and hydrolysis, the overall rate-determining step, the role of trifluoroacetic acid (TFA), as well as the influence of the stereo-configuration of amide bond and C]C bond on reaction rate.

A tris(4-methoxyphenyl)amine (TMPA)-catalyzed paired-electrolysis sulfonylation is reported. TMPA first serves as the electron donor, thereby facilitating the reduction of sulfonyl chloride; subsequently, the resulting TMPA•+ oxidizes the benzyl radical intermediate. TMPA and the chloride anion also act as a Brønsted base to promote deprotonation at the α-carbon of the sulfonyl group. The current results elucidate a novel paradigm of triarylamine multiple activation, which may stimulate continuous exploration of multiple action modes of other mediators.

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 tris(4-methoxyphenyl)amine (TMPA)-catalyzed paired-electrolysis sulfonylation is reported. TMPA first serves as the electron donor, thereby facilitating the reduction of sulfonyl chloride; subsequently, the resulting TMPA•+ oxidizes the benzyl radical intermediate. TMPA and the chloride anion also act as a Brønsted base to promote deprotonation at the α-carbon of the sulfonyl group. The current results elucidate a novel paradigm of triarylamine multiple activation, which may stimulate continuous exploration of multiple action modes of other mediators.

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.