Dong Xing

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.

Here we report a nickel/photo co-catalyzed direct radical Si–H arylation of hydrosilanes with aryl halides.

Here we report a photo/nickel co-catalyzed three-component acylarylation of alkenes using aldehydes and aryl iodides.Tetrabutylammonium decatungstate (TBADT) is used as a hydrogen-atom-transfer (HAT) photocatalyst to cooperate with nickel catalyst for this radical acylarylation. This method provides a versatile and modular strategy for synthesizing β-aryl ketones directly from readily available aldehydes under mild conditions.

The direct use of readily available aldehydes as acyl radical precursors has facilitated diverse three-component acylative difunctionalization reactions of alkenes, offering a powerful route to synthesize β-branched ketones. However, asymmetric three-component acylative difunctionalization of alkenes with aldehydes still remains elusive. Here we report a copper-catalyzed asymmetric three-component radical acylarylation of vinylarenes with aldehydes and aryl boronic acids. This method begins with acyl radical formation from an aldehyde via hydrogen atom transfer. The acyl radical adds to the alkene, forming a new benzylic radical that then undergoes copper-catalyzed enantioselective arylation. A chiral binaphthyl-tethered bisoxazoline ligand is essential for achieving high stereocontrol. This strategy enables the direct synthesis of a range of synthetically valuable chiral β,β-diaryl ketones from aldehydes and vinylarenes.

This paper highlights the latest advancements in asymmetric alkylative difunctionalization of carbon–carbon double bonds by utilizing aliphatic C─H substrates as alkyl radical precursors. By integrating different hydrogen atom transfer (HAT) processes with various transition metal catalytic systems, various alkane substrates can be efficiently converted into corresponding alkyl radicals, which then participate in radical additions to carbon–carbon double bonds followed by stereoselective functionalizations with a third component. These strategies leverage inexpensive, abundant, and readily available alkane feedstocks to rapidly construct complex chiral molecules, demonstrating high step and atom economy. This paper focuses on recent progress and applications in this area, provides a comprehensive perspective on current developments, and suggests future directions in alkane‐involved asymmetric transformations.