Pd-catalyzed hydrophosphorylation of alkynes with P(O)−H compounds provided atom-economical and oxidant-free access to alkenylphosphoryl compounds. Nevertheless, the applicable P(O)−H substrates were limited to those without a hydroxyl group except H2P(O)OH. It is also puzzling that Ph2P(O)OH could co-catalyze the reaction to improve Markovnikov selectivity. Herein, a computational study was conducted to elucidate the mechanistic origin of the phenomena described above. It was found that switchable mechanisms influenced by the acidity of substrates and co-catalysts operate in hydrophosphorylation. In addition, potential side reactions caused by the protonation of PdII−alkenyl intermediates with P(O)−OH species were revealed. The regeneration of an active Pd(0) catalyst from the resulting Pd(II) complexes is remarkably slower than the hydrophosphonylation, while the downstream reactions, if possible, would lead to phosphorus 2- pyrone. Further analysis indicated that the side reactions

The carbon dioxide (CO2) capture and utilization has attracted a great attention in organic synthesis. Herein, an unpresented transient stabilization effect (TSE) of CO2 is disclosed and well applied to the electrochemical hydrogenation of azo compounds to hydrazine derivatives. Mechanistic experiments and computational studies imply that CO2 can capture azo radical anion intermediates to protect the hydrogenation from potential degradation reactions, and is finally released through decarboxylation. The promotion effect of CO2 was further demonstrated to work in the preliminary study of electrochemical reductive coupling of α-ketoesters to vicinal diol derivatives. For the electrochemical reductive reactions mentioned above, CO2 is indispensable. The presented results shed light on a different usage of CO2 and could inspire novel experimental design by using CO2 as a transient protecting group.

A mechanistic investigation of α-alkynylation and α- allenylation of aldehydes under the synergistic catalysis of AuCl/ amine was performed using density functional theory (DFT) calculations. For such a reaction that delivers two products, this study reveals that the reaction undergoes such a mechanistic mode: reactants → alkynyl product → allenyl product, implying that the allenyl product cannot be obtained directly from reactants. The product ratio obtained experimentally was rationalized based on the computed results that both products can reversibly interconvert with AuCl as the catalyst and with N-containing Lewis bases as additives such as 4,5-diazafluorenone. For the relative stability of alkynyl versus allenyl compounds, unsaturated substituents are found to favor the allenyl compounds.

Density functional theory (DFT) calculations have been conducted to study the mechanisms, substituent effects, and the role of bases in Au- and Cu-catalyzed hydroacylation of terminal alkyne with glyoxal derivatives. The two reactions, despite being catalyzed by the same group of transition metals, follow distinctive reaction mechanisms. Through the detailed DFT calculations, insights into the mechanisms are obtained, and the substituent effects and the role of the bases are understood.

Nickel/photoredox dual catalyzed cross-coupling of aryl halides with alkylboron compounds is one of the effective methodologies for the construction of C(sp2) C(sp3) bonds. Although elegant results have been achieved by using alkyl trifluoroborates as alkyl radical precursors, the generation of alkyl radicals from readily available alkyl boronic esters is still limited due to their high oxidation potential. We disclosed here that activation of alkyl boronic esters by MeOLi is highly efficient for the generation of alkyl radicals under photocatalysis conditions. The reaction featured with a wide substrate scope, high functional group tolerance, and late-stage modification of bioactive substances. In addition, the method was also successfully extended to alkyl boronic acids. Experimental and computational mechanistic studies indicated that the crosscoupling likely proceeds via a Ni(I)-catalyzed pathway.

α-Heteroatom-substituted amides are useful as both targets and intermediates but are challenging to synthesize via conventional enolate chemistry. Herein, we describe a general and unified umpolung procedure to prepare α-heteroatom-functionalized secondary amides with various heteroatom-based nucleophiles under redox-neutral conditions. This transformation is a formal oxidation state reshuffle process from -N to -C in the hydroxamate, thereby achieving the umpolung α-heterofunctionalization of carbonyl groups without external oxidants. Regulated by the reshuffle mechanism, functionalization exclusively occurs at the α-position of the hydroxamate and precisely affords the α-functionalized amide with reliable predictability even in complex settings. Density functional theory studies support that soft enolization enabled by Mg2+/DIPEA combination is essential to facilitate the formation of the α-lactam intermediate. This represents the first general protocol to prepare α-functionalized se

The classic Curtius rearrangement provides an efficient method for converting carboxylic acids into amine derivatives but has safety concerns. Herein, we report a general and powerful method for the direct decarboxylative C–N coupling of alkyl and aryl carboxylic acids with dioxazolones in the presence of a base. A diverse array of amides, especially acylated chiral amines, can be synthesized under transition-metal-free conditions at room temperature, offering an alternative to the classic Curtius rearrangement. On the basis of mechanistic investigations, a distinctive mechanism involving multiple nucleophilic addition–eliminations, acyl transfers and a Lossen-type rearrangement is proposed for this unpredicted stereoretentive transformation.

Flavin-dependent catalysts are widely applied to aerobic monooxygenation/oxidation reactions. In contrast, flavin-catalyzed aerobic dioxygenation reactions exhibit higher atomic economy but are less reported, not to mention the relevant mechanistic studies. Herein, a density functional theory study on flavin-catalyzed aerobic epoxidation-oxygenolysis of alkenyl thio-esters was performed for the first time. Different from the previous mechanistic proposal, a pathway featuring two catalytic stages, monoanionic flavin-C(4a)-peroxide/oxide intermediates, and a reverse reaction sequence (epoxidation goes prior to oxygenolysis) was revealed. In comparison, the pathways involving dianionic flavin catalysts, monoanionic flavin-N(5)-(hydro)peroxide/C-(10a)-peroxide, or neutral flavin-C(4a)-hydroperoxide/hydroxide/N(5)-oxide, and the pathways where oxygenolysis goes prior to epoxidation are less favored. Epoxidation goes through intramolecular substitution of the O−O bond of anionic flavin-C(4a)

Nickel/photoredox dual catalyzed cross-coupling of aryl halides with alkylboron compounds is one of the effective methodologies for the construction of C(sp2) C(sp3) bonds. Although elegant results have been achieved by using alkyl trifluoroborates as alkyl radical precursors, the generation of alkyl radicals from readily available alkyl boronic esters is still limited due to their high oxidation potential. We disclosed here that activation of alkyl boronic esters by MeOLi is highly efficient for the generation of alkyl radicals under photocatalysis conditions. The reaction featured with a wide substrate scope, high functional group tolerance, and late-stage modification of bioactive substances. In addition, the method was also successfully extended to alkyl boronic acids. Experimental and computational mechanistic studies indicated that the crosscoupling likely proceeds via a Ni(I)-catalyzed pathway.

α-Heteroatom-substituted amides are useful as both targets and intermediates but are challenging to synthesize via conventional enolate chemistry. Herein, we describe a general and unified umpolung procedure to prepare α-heteroatom-functionalized secondary amides with various heteroatom-based nucleophiles under redox-neutral conditions. This transformation is a formal oxidation state reshuffle process from -N to -C in the hydroxamate, thereby achieving the umpolung α-heterofunctionalization of carbonyl groups without external oxidants. Regulated by the reshuffle mechanism, functionalization exclusively occurs at the α-position of the hydroxamate and precisely affords the α-functionalized amide with reliable predictability even in complex settings. Density functional theory studies support that soft enolization enabled by Mg2+/DIPEA combination is essential to facilitate the formation of the α-lactam intermediate. This represents the first general protocol to prepare α-functionalized se

The classic Curtius rearrangement provides an efficient method for converting carboxylic acids into amine derivatives but has safety concerns. Herein, we report a general and powerful method for the direct decarboxylative C–N coupling of alkyl and aryl carboxylic acids with dioxazolones in the presence of a base. A diverse array of amides, especially acylated chiral amines, can be synthesized under transition-metal-free conditions at room temperature, offering an alternative to the classic Curtius rearrangement. On the basis of mechanistic investigations, a distinctive mechanism involving multiple nucleophilic addition–eliminations, acyl transfers and a Lossen-type rearrangement is proposed for this unpredicted stereoretentive transformation.

Flavin-dependent catalysts are widely applied to aerobic monooxygenation/oxidation reactions. In contrast, flavin-catalyzed aerobic dioxygenation reactions exhibit higher atomic economy but are less reported, not to mention the relevant mechanistic studies. Herein, a density functional theory study on flavin-catalyzed aerobic epoxidation-oxygenolysis of alkenyl thio-esters was performed for the first time. Different from the previous mechanistic proposal, a pathway featuring two catalytic stages, monoanionic flavin-C(4a)-peroxide/oxide intermediates, and a reverse reaction sequence (epoxidation goes prior to oxygenolysis) was revealed. In comparison, the pathways involving dianionic flavin catalysts, monoanionic flavin-N(5)-(hydro)peroxide/C-(10a)-peroxide, or neutral flavin-C(4a)-hydroperoxide/hydroxide/N(5)-oxide, and the pathways where oxygenolysis goes prior to epoxidation are less favored. Epoxidation goes through intramolecular substitution of the O−O bond of anionic flavin-C(4a)