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

A 1,1-hydroboration of alkynylgermanes with unique transGe/B stereochemistry under transition-metal-free conditions is reported. Mechanistic studies suggest that a pathway involving α boration followed by a stepwise 1,2-Ge/H shift on the intermediate structurally lies between an alkyne−Ge+ π complex and a typical vinyl cation. The resulting Ge/B bimetallic modules, along with a Ge*/Ge/B trimetallic variant, can be conveniently transformed into trisubstituted olefins through iterative divergent cross-coupling. This work demonstrates that incorporating metalloids into classical organic reactions may offer unconventional chemical selectivity and efficient synthetic applications.

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.

A 1,1-hydroboration of alkynylgermanes with unique transGe/B stereochemistry under transition-metal-free conditions is reported. Mechanistic studies suggest that a pathway involving α boration followed by a stepwise 1,2-Ge/H shift on the intermediate structurally lies between an alkyne−Ge+ π complex and a typical vinyl cation. The resulting Ge/B bimetallic modules, along with a Ge*/Ge/B trimetallic variant, can be conveniently transformed into trisubstituted olefins through iterative divergent cross-coupling. This work demonstrates that incorporating metalloids into classical organic reactions may offer unconventional chemical selectivity and efficient synthetic applications.

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.