Zhang Xingang, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, and Kendall n. Houk, UCLA, have made new progress in metal Difluorocarbene chemistry

Zhang Xingang group of Shanghai Key Laboratory of organic chemistry, Chinese Academy of Sciences and Kendall n Houk group of Los Angeles University, California, USA, have completed the regulation of Difluorocarbene nucleophilic and electrophilic reactivity through palladium metal for the first time, which can be used in organic synthesis in a controlled way, thus realizing the "control" of Difluorocarbene The nucleophilic and electrophilic PD Difluorocarbene ([PD] = CF 2) can coexist in the same reaction system through the valence regulation of Pd metal, and can control the catalytic cycle to selectively generate different reaction products This work was recently published in nature Chemistry (DOI: 10.1038 / s41557-019-0331-9) Researcher Zhang Xingang and Professor Kendall n Houk are co correspondents, and Dr Fu Xiaping and Dr Xue Xiaosong, visiting scholars of the research group of Professor Houk and Shanghai Institute of organic chemistry, Chinese Academy of Sciences, are co first authors Professor Houk and Dr Xue Xiaosong are responsible for theoretical calculation, and Shanghai Institute of organic chemistry, Chinese Academy of Sciences is the first communication unit Difluorocarbene is an important intermediate in chemical industry Its preparation route is mature and it is widely used in the synthesis of fluorine-containing materials, such as Teflon From the perspective of organic synthesis route design, Difluorocarbene will be an important synthon if it has the reaction diversity similar to the traditional non-fluorocarbene intermediates It is widely used in the efficient synthesis of fluorine-containing pharmaceuticals, pesticides and materials with special properties and different structures However, the intrinsic high electrophilicity of Difluorocarbene makes its reaction type rather limited, and its active reactivity makes it difficult for Difluorocarbene to be used in controllable organic synthesis reactions Therefore, how to "tame" and "control" Difluorocarbene, a wild horse, and realize its wide application in organic synthesis through reactive regulation has always been a challenging problem in organic fluorine chemistry Theoretically, the complexation of transition metals with Difluorocarbene will change the electron cloud distribution of Difluorocarbene, thus providing the possibility for its reactivity regulation However, it is known that the separated transition metal Difluorocarbene complexes are inert, and the catalytic cycle reactions in which Difluorocarbene is involved are rarely reported, and there is a lack of theoretical understanding and understanding in the industry, so that the use of Difluorocarbene has not been realized in the widely used catalytic coupling reactions Until 2016, Zhang Xingang group of Shanghai Institute of organic Sciences, Chinese Academy of Sciences, used palladium as catalyst to discover the first case of catalytic coupling reaction (medic) involving metal Difluorocarbene (org Lett 2016, 18, 44), and realized the first case of efficient catalytic conversion of dichlorodifluoromethane (nature chemistry 2017, 9, 918) On the basis of the above research, the research group realized the regulation of Difluorocarbene reactivity by changing the valence of central transition metal for the first time, making Difluorocarbene have nucleophilic or electrophilic reactivity under different metal valence, and then realized the catalytic controllable synthesis of different fluorine-containing compounds Based on this concept, they used palladium as a catalyst to obtain brcf 2PO (OET) 2 As the precursor of Difluorocarbene, the selective fluoroalkylation of arylboric acid compounds is realized; through the fine control of reaction conditions, the controllable synthesis of four fluorine-containing compounds can be realized, including difluoromethyl, tetrafluoroethyl aromatic compounds, aryldifluoromethyl and aryltetrafluoroethyl ketones This series of metal Difluorocarbene participated in the controllable catalytic coupling reaction with excellent functional group compatibility, which can selectively modify the complex medicine and pesticide molecules in the later stage, and can synthesize different fluorine-containing compounds in one pot at the same time, providing an efficient and simple method for the research and development of new drugs Combined with elementary reaction, computational chemistry and separation of key metal reaction intermediates, it is found that nucleophilic and electrophilic [PD] = CF 2 species exist in the reaction system at the same time, in which, for the first time, they separated the zero valent palladium Difluorocarbene complex [PD 0] = CF 2, and proved that it is highly nucleophilic and can react with water molecules in protonation This is the only metal Difluorocarbene species that can be protonated with water However, PD Difluorocarbene complex [PD II] = CF 2 is electrophilic and can react with water to form Co These findings lay an important theoretical foundation for the catalytic coupling reaction of PD Difluorocarbene, provide a new perspective for understanding other metal Difluorocarbene chemistry, and open a new path for the regulation of Difluorocarbene reactivity The research was supported by the National Natural Science Foundation of China and the strategic leading science and technology program of the Chinese Academy of Sciences (category B)