Shi-Liang Shi

C–N axially chiral heterobiaryls are highly valuable yet synthetically challenging scaffolds. Atroposelective hydroarylation represents an ideal strategy for their construction, offering both high step- and atom-economy. Herein, we report an enantio- and regioselective Ni-catalyzed hydroarylation of unactivated alkenes for the efficient synthesis of C–N axially chiral heterobiaryls. The sterically demanding chiral N-heterocyclic carbene (NHC) ligands enable excellent control over regioselectivity and enantioselectivity, affording a broad range of axially chiral products in good to excellent yields with up to 98% ee. The reaction exhibits broad substrate scope and high functional-group tolerance. Furthermore, the catalytic strategy could be extended to the atroposelective hydroarylation of alkynes, providing direct access to axially chiral alkenyl heterobiaryls with excellent chemo-, regio-, enantio- and E/Z-selectivity. Notably, the use of MeONa proved crucial for precise control of alkene geometry. This study provides a robust platform to advance the development of atroposelective hydroarylation reactions, enabling the construction of a series of novel C–N axially chiral scaffolds.

Trifluoromethylated quaternary centers are privileged structural motifs in bioactive molecules, rendering their catalytic asymmetric construction a highly sought-after synthetic target. Herein, we report an N-heterocyclic carbenes (NHC)-catalyzed intermolecular annulation reaction, providing efficient access to trifluoromethyl quaternary stereocenter with high yield, diastereoselectivity and enantioselectivity. The use of ANIPE ligand is crucial in achieving high efficiency and stereocontrol.

Despite the widespread occurrence of enantiomerically enriched tertiary alcohols in bioactive molecules and pharmaceuticals, efficient methods for preparing optically pure α,β-stereogenic tertiary alcohols remain scarce. Here, we report a dynamic kinetic asymmetric allylation of readily available racemic ketones with 2-aza-1,4-dienes. Notably, through the judicious selection of chiral ligands for copper catalysts, both E- and Z-isomers can be accessed with high efficiency and stereocontrol. Density functional theory (DFT) calculations reveal that ligand-controlled face-selective attacks via distinct allylcopper intermediates dictate the stereodivergent E/Z selectivity. This reaction achieves excellent diastereo- and enantioselectivity, accommodates a broad range of heterocyclic substrates, and exhibits extensive functional group tolerance. We demonstrate the utility of this protocol by modifying Profen-type drugs and rapidly synthesizing complex drug molecules. This study provides a versatile and efficient route to diverse chiral tertiary alcohols, offering a powerful tool for pharmaceutical assembly.

Asymmetric carbothiolation of alkenes represents a highly efficient, yet underexplored, strategy for the direct construction of chiral thioethers. Herein, we report a palladium-catalyzed enantio- and regio-selective carbothiolation of alkenes via C−S bond activation and migratory insertion. Leveraging a chiral N-heterocyclic carbene ligand, this method provides access to chiral indole derivatives featuring quaternary stereocenters atom-, step-, and redox-economically. The reaction is applicable to a broad range of substrates, providing the corresponding products in up to 99% yield and up to 97% e.e.. Mechanistic investigations reveal that oxidative addition of the C−S bond is the enantio-determining step, while the subsequent reductive elimination serves as the rate-determining step.

We report a highly enantio- and diastereoselective reductive coupling of unactivated alkenes with aldehydes catalyzed by an N-heterocyclic carbene (NHC)/nickel complex, which provides efficient access to optically active indanol derivatives. Under mild conditions, a broad range of substrates bearing diverse functional groups─including electron-donating, electron-withdrawing, and heteroaromatic substituents─underwent smooth coupling to afford the corresponding products with excellent stereocontrol (all >99:1 dr, up to 97% ee). The method was also successfully extended to ketone substrates, delivering chiral tertiary alcohol derivatives with good enantioselectivity, further demonstrating its synthetic versatility. The use of a bulky chiral NHC ligand proved to be essential for achieving high stereoselectivity in the nickel-catalyzed process.

Grignard reagents—cornerstones of synthetic chemistry—are hindered by enduring limitations in accessing complex architectures, which poses a persistent synthetic bottleneck. Meanwhile, quaternary carbon (stereo)centres, ubiquitous in bioactive molecules and natural products, remain formidable synthetic targets despite decades of research. Here we introduce a nickel-catalysed carbomagnesiation strategy that simultaneously overcomes these challenges through a rare contra-electronegativity transmetallation (Ni to Mg). This approach enables the efficient and modular synthesis of β-quaternary Grignard reagents via carbomagnesiation of 1,1-disubstituted alkenes and 1,3-dienes, employing aryl triflate and PhMgBr as carbon and magnesium sources, respectively. The resulting organomagnesium reagents undergo one-pot reactions with diverse electrophiles, delivering stereochemically complex quaternary centres with high precision. Mechanistically, bulky N-heterocyclic carbene (NHC)-based catalysts divert classical cross-coupling pathways, enforcing a counterintuitive Ni-to-Mg transmetallation that defies conventional electronegativity trends while achieving exceptional regio- and enantiocontrol. This contra-electronegativity transmetallation demonstrates substantial potential to advance carbometallation reactions and open new avenues for cross-coupling chemistry.

Fluorinated small molecules and polymers are widely used in pharmaceuticals, agrochemicals, and materials science. Yet, their unified, highly efficient preparation from abundant feedstocks with excellent atom-, step-, and redox-economy remains elusive. Herein, we report a highly regioselective hydroarylation of diverse alkenes with polyfluoroarenes. This transformation is mediated by a rationally designed unsymmetric N-heterocyclic carbene (NHC) ligand, whose distinct steric profile accelerates both C–H activation and reductive elimination, affording superior reactivity and selectivity. Furthermore, this catalytic paradigm is extended to the direct C–H polyaddition of dienes and diynes, yielding copolymers with exceptional thermal stability and tunable fluorescence properties. Notably, this protocol aligns with the principles of sustainable chemistry, characterized by 100% atom economy, high step economy, and the absence of pre-functionalized reagents. This study establishes a versatile platform for the C–H functionalization and polymerization of polyfluoroarenes, paving the way for advancing polymer synthesis via C–H polyaddition strategies.

The intermolecular carbo-halogenation of alkenes provides a direct method for synthesizing alkyl halides. However, existing methods are largely limited to monosubstituted alkenes, and a general catalytic asymmetric intermolecular variant remains an unsolved challenge. Herein, we report a highly regio- and enantioselective intermolecular carbo-halogenation of 1,1-disubstituted alkenes through a nickel/N-heterocyclic carbene (NHC)-catalyzed carbo-magnesiation/electrophilic halogenation strategy. The use of bulky NHC ligands and haloacetonitriles as halogen sources proved crucial for achieving high reactivity and selectivity, facilitating the efficient synthesis of diverse alkyl halides that feature acyclic or cyclic β-all-carbon quaternary centers. This work significantly advances the field of catalytic asymmetric carbo-halogenation.