Copper Catalyzed Enantioconvergent Nucleophilic Substitutions

• Published in: Chinese journal of chemistry Vol. 42; no. 10; pp. 1161 - 1174
• Main Authors: Huang, Chunxi, Wan, Zilong, Zhu, Aoping, Chen, Caiyou
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 15.05.2024; Wiley Subscription Services, Inc
• Subjects: Anions; Asymmetric catalysis; Binding sites; Catalysis; Catalysts; Copper; Deoxygenation; Electrode potentials; Enantioconvergent; Formations; Guanidine; Halides; Heavy metals; Ligands; Nucleophiles; Nucleophilic substitution; Photocatalysis; Radical reactions; Side reactions; Tertiary; Transition metals
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202300622

Comprehensive Summary As a versatile earth‐abundant transition metal, Cu has long been widely applied in the C—C and C—X bond forming reactions. As for now, low‐valent Cu(I) is known to reduce the redox active electrophiles via an SET pathway to give the corresponding radical and Cu(II) species. The resulting Cu(II) species can interact with the radical via the out‐sphere pathway, affording the coupling product. Alternatively, Cu(II) can trap the radical through the inner‐sphere process to generate Cu(III) species and then realize challenging bond formations due to the facile reductive elimination of Cu(III) intermediate. Although copper catalysis has been widely applied in arylations of various nucleophiles, copper‐catalyzed enantioconvergent nucleophilic substitutions of racemic alkyl electrophiles have been less explored, likely due to the difficulties in overcoming the reduction potential of alkyl electrophiles, elimination of side reactions, and enantiomeric control. In order to overcome the high reduction potential of alkyl electrophiles, the photo‐induced strategy has been developed under mild conditions. An alternative strategy with new anionic tridentate ligands has also been reported in this regard. This review summarizes recent developments in copper‐catalyzed enantioconvergent nucleophilic substitutions of alkyl electrophiles by various nucleophiles to realize C—N, C—C, C—B, C—P and C—O bond formations and their brief mechanistic studies. Key Scientists In 2016, Fu and Peters et al. reported the first photo‐induced Cu‐catalyzed enantiocovergent C—N bond formations of tertiary alkyl halides with N‐hetereocycles, opening the door for the Cu‐catalyzed enantiocovergent nucleophilic substitutions. The photo‐induced strategy has been developed that greatly enhances the reducing power of Cu(I). The Cu‐catalyzed enantioconvergent cyanation (decarboxylative) and borylation were then successively presented by Liu and Ito in 2017 and 2018, respectively. Other than the photo‐induced strategy, Liu et al. in 2019 demonstrated that anionic ligands can also significantly enhance the reducing ability of Cu(I). The cinchona‐based chiral anionic tridentate ligands have been utilized for a series of Cu‐catalyzed enantiocovergent nucleophilic substitutions. Zhang et al. also developed chiral anionic tridentate ligands containing the oxazoline binding sites in 2020. In 2020, Xiao and Lu et al. reported the Cu‐catalyzed enantiocovergent deoxygenative cyanation. Later in 2022, Feng and Liu et al. developed the new guanidine hybrid ligands. This review focuses on the Cu‐catalyzed enantioconvergent nucleophilic substitutions that emerged in recent years.