Jian Zhou

We report the highly enantioselective nucleophilic addition reaction of simple ketone-derived hydrazones. Accordingly, a ErCl₃-catalyzed cyanation of both aliphatic and aryl ketone hydrazones is achieved for the facile access of C ^α -tetrasubstituted α-hydrazino nitriles in up to 96% ee, by using the sterically confined pyridinebisoxazoline (PYBOX) ligand featuring a sulfonyl group at the pyridine C4 position. This method enables the shortest catalytic enantioselective total synthesis of L-carbidopa , a drug that could treat the symptoms of Parkinson’s disease, with 82% overall yield in four steps. These adducts are valuable synthons to various α-tertiary hydrazines and related azacycles that are interesting targets for medicinal studies and pesticide research. From our biological analysis, a chiral α-hydrazino nitrile with good insecticidal activity against Aphis gossypii (LC ₅₀ = 15.11 mg∙L ^–1 ) was identified, rivaling commercial insecticides.

Flow chemistry has become an important tool for manufacturing nowadays, driven by the growing demand for safety, efficiency, scale, and sustainability in chemical industries. Building on basic flow chemistry techniques, multistep continuous flow synthesis has emerged as an attractive synthetic process in pharmaceutical, agricultural, and materials synthesis. In practice, numerous issues need to be addressed in multistep continuous flow processes, such as reaction compatibility, step-connection, material transfer, and flow stability. Aiming to establish an industrially viable multistep flow process for tiadinil, methiadinil, emamectin benzoate and other drug molecules in agricultural and pharmaceutical industry, we cooperated with enterprises in the past few years and encountered nearly all the difficulties that may arise in the process, and these difficulties are also long-standing challenges for industry settings. To tackle these barriers faced, we developed and searched for various solutions to address them. These practices further facilitated the formulation of the common solutions for developing a multistep continuous flow process. This perspective will integrate relevant literature with our research to showcase the key challenges in multistep continuous flow synthesis and discuss corresponding solutions. Additionally, general development of flow process usually begins with extensive screenings of reaction conditions in batch before further optimization in flow. Instead, a more efficient approach called de novo flow, defined as performing reaction optimizations primarily in flow after feasibility has been established in batch, has been emerging as a viable strategy. We also present an outlook on the forthcoming development of multistep continuous flow synthesis and point out the key issues to be addressed in the future.

The development of asymmetric catalytic methods using CO2 as a C1 synthon is an important strategy for constructing chiral carboxylic acids and heterocyclic compounds. In recent years, through the design of innovative catalytic systems, efficient and highly selective syntheses of chiral carboxylic acids, spanning central to axial chirality, have been achieved from diverse substrates, including alkenes, alkynes, and organic electrophiles. Concurrently, significant progress has also been made in the synthesis of chiral heterocycles, particularly 2-oxazolidinones and cyclic carbonates. This review systematically summarizes key advances in this field from 2021 to mid-2026. Organized by target product structure, the discussion first addresses chiral carboxylic acids, categorized by substrate type (carbon-carbon unsaturated bonds and organic electrophiles). Key strategies, including carbo-carboxylation, boracarboxylation, hydrocarboxylation, dicarboxylation, and electroreductive carboxylation, are elaborated in detail, along with their stereoselectivity control mechanisms. The discussion then covers chiral heterocycles, summarizing the catalytic asymmetric construction of chiral 2-oxazolidinones and chiral cyclic carbonates. Finally, the major challenges and future directions in this field are discussed.

An electrochemical meta-C-H silylation of pyridines with readily available hydrosilanes is described. The reaction proceeds under mild conditions without noble metal catalysts or external oxidants using N-hydroxyphthalimide as a hydrogen-atom-transfer catalyst. In addition, quinolines and pyrazines are well tolerated, affording the corresponding silyl-functionalized azines.

2-Trifluoromethylated aromatic azacycles such as quinoline and pyridine derivatives are interesting targets for the development of new drugs and agrochemicals. The direct C-H trifluoromethylation of aromatic azacycles using trimethyl(trifluoromethyl)silane (TMSCF ₃ ) constitutes a facile approach for the C2-regioselective incorporation of a trifluoromethyl group into aromatic azacycles, but the yield and substrate scope wait for further improvement. Herein, we report an improved C2-regioselective trifluoromethylation of quinoline derivatives using Me ₂ (CH ₂ Cl)SiCF ₃ . Under a modified condition of Kanai & Kuninobu procedure involving sequential nucleophilic addition/oxidative aromatization process, an array of 2-CF ₃ substituted quinoline derivatives (24 examples) could be obtained in good to excellent yields, obviously higher than those obtained by using TMSCF ₃ (the yield increment of 10 examples was no less than 20%). Obviously enhanced yield is also observed in the 2-trifluoromethylation of naphthyridine and phenanthroline derivatives. These results imply that modifying the methyl group of TMSCF ₃ by a suitable polar substituent may contribute to more powerful silyl trifluoromethylating reagents for the selective incorporation of a CF ₃ group into aromatic azacycles.

This tutorial review discusses the role of C–F⋯H–X hydrogen-bonding interactions in enabling new reactivity, as well as enhancing the regioselectivity and enantioselectivity of organic reactions.

A one-pot tandem aldol/desilylation/CuAAC sequence is developed, allowing facile synthesis of tertiary alcohols featuring an α-difluoroketone moiety and a 1,2,3-triazole at the α position in moderate to good yields, with an operationally friendly manner. While Bi(OTf)₃ was the optimal catalyst for the Mukaiyama-aldol reaction of silyl-α-ketoalkynes and difluoroenoxysilanes, CuCl was found to efficiently mediate the alkyne-azide cycloaddition. Received: 10 July 2025 Accepted after revision: 02 September 2025 Accepted Manuscript online: 19 September 2025 © . Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany