Recently, Professor Shi Dayong's Team at the State Key Laboratory of Microbial Technology of Shandong University published a research paper entitled "Nickel-Catalyzed Stereoselective Cascade C-F Functionalizations of gem-Difluoroalkenes" in ACS Catalysis. PhD Li Xiaowei is the first author. Professor Shi Dayong is the corresponding author, and Shandong University is the first author institution and the corresponding author institution.

The carbon-fluorine (C-F) bonds are among the strongest and most unreactive covalent single bonds owing to the small size and profound electronegativity of fluorine atoms. The selective functionalization of C-F bonds has thus been of long-standing interest in diverse fields of chemistry. Over the past decades, the chemical modification of organic fluorocompounds involving a C-F bond activation has been extensively achieved. However, successively replacing two fluorine atoms from a multi-fluorinated compound while maintaining high chemoselectivity has scarcely been documented to date. In particular, the replacement of two fluorine atoms with different functional groups in one pot remains undeveloped and would thus be of great significance. The key issues are related to the extremely similar high energy between the two C-F bonds, the more crowded steric environment, the difficulty in controlling self-dimerization and cross-selectivity, the poorer stability of alkene reaction partners, as well as chemo- and stereoselectivity.

The easily accessible gem-difluoroalkenes have emerged as valuable synthetic intermediates in various intriguing transformations and can be used as an ideal precursor for dual C-F bond activation. In seeking a solution to achieve catalytic dual C-F bond functionalization of gem-difluoroalkenes, we were drawn to reductive cross-coupling reactions. In this study, the authors achieved the first nickel-catalyzed cascade alkenylation/deuteration of gem-difluoroalkenesin one pot by successive defluorination using manganese powder as a reducing agent and alkenyl triflates and D₂O as bifunctionalization reagents. In addition, deuterated compounds play an important role in numerous areas, including pharmaceutical discovery and development, mechanistic investigations, and spectroscopic studies. Since alkenes are one of the most basic and prevalent substructures in drugs and bioactive molecules, the synthetic procedures of deuterated alkenes as building blocks are of considerable importance. This methodology offers facile access to various deuterated1, 3-dienes with broad functional group compatibility and (E)-selectivity under mild conditions, providing a new option for the synthesis of diverse deuterated alkenes. Moreover, the application in the modification of complex molecules,gram-scale reactions, and synthetic transformations clearly proved the synthetic utility of this process.

This work was supported by the Funded by National Program for Support of Top-Notch Young Professionals, the National Key Research and Development Program of China, the Joint Fund of Shandong Natural Science Foundation, Qingdao Science and Technology Benefit People Demonstration Guide Special Project, Qingdao emerging industry cultivation project, and Basic and Applied Basic Research Foundation of Guangdong Province. We thank Sui Haiyan and Li Xiaoju from Shandong University Core Facilities for Life and Environmental Sciences for their help with the NMR.

Link to the article:https://pubs.acs.org/doi/full/10.1021/acscatal.3c00047

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