The reaction mechanism of gold(I)-catalyzed cascade reaction of aminaloalkynes involving PetasisFerrier arrangement was studied with the aid of density functional theory calculations. Our study showed that two mechanisms proposed by the Patil group and by us are possible. With the substrate bearing a -C≡C-H component the mechanism by us is preferred in which the reaction undergoes first a Petasis-Ferrier rearrangement. With the substrate bearing a -C≡C-Ar component the mechanism by the Patil group is preferred in which the reaction undergoes first a protodeauration step. In summary, both reaction mechanisms are related and reaction substrate governs which pathway is followed.

Density functional theory (DFT) calculations have been conducted to unravel the mechanisms and chemoselectivities of Au-catalyzed diazo-based couplings with phenyl unsaturated aliphatic alcohols: the propargyl alcohol Ba resulting in the [4 + 1]-cycloaddition product P4a and the allyl alcohol Db giving the [2,3]-σ rearrangement species P5b. P4a formation involves a catalyst interaction with phenyldiazoacetate, N2 release, a hydroxyl O nucleophilic attack of Ba, a [1,4]-H shift, coordination isomerization, 5-endo-dig cyclization, a [4,1]-H shift and a H2O-assisted [1,3]-H shift. After the [4,1]-H shift, the slightly less favorable five-membered ring-opening possibly follows to afford trace P5a ([2,3]-σ rearrangement product), which would be kept in solution due to subsequent irreversible evolution. In addition, the Ba-involved chemoselectivity was probed and explained as follows: (i) both large HIJhydroxyl)⋯C(carbene) electrostatic repulsion and strong three-membered ring strain involved

Reactions of thiocarboxylic acids and dithiocarbamate-terminal amines provide a linker-traceless method for amide bond formation under mild conditions, whereas the reaction mechanism is not clear. A systematic study was performed herein with density functional theory (DFT) calculations to elucidate the detailed mechanism, the substitution effect on the proposed CS2-releasing 1,3-acyl transfer and the differences between CS2- and CO2-releasing 1,3-acyl transfer. Relevant results indicate that this type of reaction proceeds via the nucleophilic addition of an in situ generated dithiocarbamic acid on thiocarboxylic acid, H2S elimination, rate-determining 1,3-acyl transfer and CS2 release. For the generation of secondary amides via the 1,3-acyl transfer, a thiocarboxylic acid- or dithiocarbamic acid-assisted pathway, in which both the carbonyl group and amide nitrogen are activated, is the most favored. For the generation of tertiary amides, MeOH-assisted carbonyl-activation is the most fa

Pd-catalyzed C(sp3)−H activation/alkylation of 2-tert-butylaryl halides with alkyl halides and CH2Br2 represents an advantageous strategy for the C−H functionalization with halogens as traceless directing groups. Several possible mechanisms were proposed for the reactions, but no further evidence was available to judge their relative feasibilities. Herein, a mechanistic study was performed with the aid of density functional theory (DFT) methods. Calculations indicate that the coupling of aryl bromides with alkyl chlorides is likely to generate alkylated benzocyclobutenes via aryl−Br oxidative addition on Pd(0) catalysts, C(sp3)−H activation, alkyl−Cl oxidative addition, aryl−alkyl reductive elimination, aryl−H activation, and aryl−C(sp3) reductive elimination. The coupling of aryl iodides with CH2Br2 is likely to generate indane derivatives via aryl−I oxidative addition, C(sp3)−H activation, alkyl−Br oxidative addition, aryl−CH2Br reductive elimination, alkyl−Br oxidative addition, C(s

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.