Xiaoming Feng

Professor Tang Youqi was a distinguished Chinese physical chemist and educator and one of the pioneers of structural chemistry and crystal chemistry in China

Catalytic C─H alkylation of pyrazoles with internal alkenes represents an ideal strategy for constructing functionalized pyrazoles. However, such a transformation has remained underexplored to date, likely due to the inherently low reactivity of internal alkenes and the lack of suitable catalysts. In this study, we describe a lanthanum‐catalyzed highly regioselective C─H alkylation of N ‐aryl pyrazoles with internal alkenes. The key to success of this unprecedented transformation is the use of a cationic imidazolin‐2‐iminato lanthanum catalyst, whose large ionic radius and less steric hindrance provide an open coordination environment that facilitates the coordination of sterically demanding internal alkenes to the metal center and subsequent alkene migratory insertion. Besides internal alkenes, 1,1‐disubstituted styrenes and terminal alkenes were amenable to the reaction. This protocol offers a straightforward and atom‐efficient route for the synthesis of a new family of N ‐(( ortho‐ alkyl)aryl) pyrazole derivatives (94 examples, up to 99% yield, >19:1 rr). The scale‐up synthesis and further transformation to hedgehog enzyme inhibitor analog highlight the potential application of this method. Combined experimental and computational studies elucidated the reaction mechanism and the influence of metal ion size on the turnover‐limiting alkene migratory insertion step.

Catalytic C─H alkylation of pyrazoles with internal alkenes represents an ideal strategy for constructing functionalized pyrazoles. However, such a transformation has remained underexplored to date, likely due to the inherently low reactivity of internal alkenes and the lack of suitable catalysts. In this study, we describe a lanthanum‐catalyzed highly regioselective C─H alkylation of N ‐aryl pyrazoles with internal alkenes. The key to success of this unprecedented transformation is the use of a cationic imidazolin‐2‐iminato lanthanum catalyst, whose large ionic radius and less steric hindrance provide an open coordination environment that facilitates the coordination of sterically demanding internal alkenes to the metal center and subsequent alkene migratory insertion. Besides internal alkenes, 1,1‐disubstituted styrenes and terminal alkenes were amenable to the reaction. This protocol offers a straightforward and atom‐efficient route for the synthesis of a new family of N ‐(( ortho‐ alkyl)aryl) pyrazole derivatives (94 examples, up to 99% yield, >19:1 rr). The scale‐up synthesis and further transformation to hedgehog enzyme inhibitor analog highlight the potential application of this method. Combined experimental and computational studies elucidated the reaction mechanism and the influence of metal ion size on the turnover‐limiting alkene migratory insertion step.

Dearomative photocycloaddition reactions of (hetero)arenes offer a powerful route to three-dimensional molecular scaffolds with high value in medicinal chemistry. Summarized here are recent progress on strain-release accelerated dearomative photocycloaddition with bicyclo[1.1.0]butanes and highly regio- and enantioselective [2 + 2] cycloadditions of quinolines and indole derivatives. Key to the success of the reaction is the strategic design of chiral N,N′-dioxide/metal Lewis acid catalysts with tailored steric bulk that can modulate the chiral pocket to adapt to the varied electronic and steric characteristics of different substrate substituents. The catalyst’s role and the origin of stereoselectivities were elucidated based on experimental studies and theoretical calculation.

The oxidative coupling of alkenylphenols is widespread in nature, yet chemical methods for this transformation remain underexplored. The oxidative coupling of ortho-alkenylphenols is a key step in the synthesis of benzoxanthenones; however, an enantioselective version of this process remains elusive. Here, we report an efficient bioinspired asymmetric catalytic synthesis of benzoxanthenone skeletons through the development of a type of chiral manganese-oxo catalyst. The reaction performed well using both silver oxide and air as oxidative sources for the oxidative cross-coupling of ortho-alkenyl phenols. In aerobic oxidative conditions, light was found to accelerate the generation of active high-valent manganese(IV)-oxo species, and the oxidative coupling process as well. Through various mechanistic experiments and DFT calculations, the multiple roles of the manganese-oxo catalyst are disclosed, involving HAT for vinyl radical generation, then radical-anion cross-coupling via inner-sphere one-electron oxidation, and a diastereoselective hetero-Diels–Alder reaction. The biomimetic catalytic system could find applications in other radical cyclization and redox processes.

Semisaturated heterocycles are privileged scaffolds in natural products and pharmaceuticals, yet a general and versatile catalytic strategy to access these chiral architectures remains a formidable challenge. Herein, we report a unified synthetic platform utilizing the earth‐abundant cobalt coupled with a chiral N , N ′‐dioxide ligand to unlock the tandem reactivity of vinyl carbenes for the enantioselective construction of diverse semisaturated heterocycles. We have achieved three distinct cascade transformations for modular and efficient access to 2,3‐disubstituted dihydrobenzofurans, 1,2,3‐trisubstituted indolines, and 2,3,4‐trisubstituted benzomorpholines in excellent yields, exceptional enantioselectivities, and high diastereoselectivities, respectively. Mechanistic investigations, including kinetic studies and density functional theory (DFT) calculations, have elucidated that the cascade pathway involves vinylougous C(sp ² )−H or N−H insertion of carbenoids, followed by an intramolecular conjugate addition cascade.The practical utility of this protocol is further highlighted by gram‐scale syntheses and versatile product derivatizations, offering a powerful and practical tool for the synthesis of chiral heterocycles.

Semisaturated heterocycles are privileged scaffolds in natural products and pharmaceuticals, yet a general and versatile catalytic strategy to access these chiral architectures remains a formidable challenge. Herein, we report a unified synthetic platform utilizing the earth‐abundant cobalt coupled with a chiral N , N ′‐dioxide ligand to unlock the tandem reactivity of vinyl carbenes for the enantioselective construction of diverse semisaturated heterocycles. We have achieved three distinct cascade transformations for modular and efficient access to 2,3‐disubstituted dihydrobenzofurans, 1,2,3‐trisubstituted indolines, and 2,3,4‐trisubstituted benzomorpholines in excellent yields, exceptional enantioselectivities, and high diastereoselectivities, respectively. Mechanistic investigations, including kinetic studies and density functional theory (DFT) calculations, have elucidated that the cascade pathway involves vinylougous C(sp ² )−H or N−H insertion of carbenoids, followed by an intramolecular conjugate addition cascade.The practical utility of this protocol is further highlighted by gram‐scale syntheses and versatile product derivatizations, offering a powerful and practical tool for the synthesis of chiral heterocycles.