The reaction features combination of C–H activation and ring opening of cyclopropanol was studied with the aid of DFT calculations. With the reaction of N-pyrimidylindoline and 1-benzylcyclopropanol as an example to accomplish the alkylation, we found the order of C–H activation/ring opening is difficult to occur. Instead, the order of ring opening/C–H activation is predicted to be more reasonable, which circumvents the N→Rh bond breaking. Two catalytic cycles were suggested. The first cycle relates to the catalytic oxidation of cyclopropanol by Cu(II) to generate an intermediate product, the vinyl ketone. The mechanism mainly involves prior ring opening of cyclopropanol and β-H elimination. The second cycle relates to the product formation from the resultant intermediate product, in which the C–H activation of N-pyrimidylindoline, C– –C bond insertion of the intermediate product and protonation are included. The insights gained in this study are expected to be pertinent in other react

The control of regioselectivities has been recognized as the elementary issue for alkene hydroboration. Despite considerable progress, the specificity of alkene substrates or the adjustment of ligands was necessary for specific regioselectivities, which restrict the universality and practicability. Herein, we report a ligand-free iron-catalyzed regiodivergent hydroboration of aliphatic terminal alkenes that obtains both Markovnikov and anti-Markovnikov hydroboration products in high regioselectivities. Notably, solvents and bases were shown to be crucial factors influencing the regioselectivities and further studies suggested that the iron−boron alkoxide ate complex is the key intermediate that determines the unusual Markovnikov regioselectivity. Terminal alkenes with diverse structures (monosubstituted and 1,1-disubstituted, open-chain and exocyclic) underwent the transformation smoothly. The reaction does not require the addition of auxiliary ligands and it can be performed on a gram

Ru-catalyzed cross-coupling of secondary alcohols with only byproducts H2 and H2O provides a green synthetic strategy to prepare β-disubstituted ketones. Density functional theory (DFT) calculations were performed with the coupling of 1-phenylethanol and cyclohexanol as a model reaction to gain deeper mechanistic insights herein. The mechanistic details of the main reaction and the key steps of possible side reactions were clarified, and the obtained results are consistent with reported selectivity. Hydrogenation of α,β-unsaturated ketones and dehydrogenation of ruthenium hydride intermediate are direct chemoselectivity-determining stages. The hydrogenation via 1,4-addition generates more stable intermediates, being favored over that via 1,2-addition, and thus avoids the formation of alkene products. The conjugation and π−π stacking effects of phenyl and the weak electronic effect of alkyls explain the dominance of specific ketone products in the hydrogenation stage. Hydrogenation of k

An efficient and eco-friendly protocol for the construction of naphtho[2,1-d]thiazol-2-amines through visible-light photoredoxcatalyzed C(sp2)–H/S–H cross-dehydrogenative coupling reactions between 2-isothiocyanatonaphthalenes and amines was established. In this reaction, the new C–N and C–S bonds are formed simultaneously in a single step. This new method provides a straightforward approach for constructing valuable sulfur-containing compounds.

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.