Asymmetric three-component olefin dicarbofunctionalization enabled by photoredox and copper dual catalysis

• Published in: Nature communications Vol. 12; no. 1; pp. 1815 - 10
• Main Authors: Wang, Peng-Zi, Gao, Yuan, Chen, Jun, Huan, Xiao-Die, Xiao, Wen-Jing, Chen, Jia-Rong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 639/638/403/933; 639/638/403/934; 639/638/77/888; Alkenes; Asymmetry; Carbon; Catalysis; Copper; Cross coupling; Enantiomers; Esters; Humanities and Social Sciences; Ketones; multidisciplinary; Optical activity; Oxime esters; Radicals; Science; Science (multidisciplinary); Single electrons
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22127-x

The intermolecular three-component alkene vicinal dicarbofunctionalization (DCF) reaction allows installation of two different carbon fragments. Despite extensive investigation into its ionic chemistry, the enantioseletive radical-mediated versions of DCF reactions remain largely unexplored. Herein, we report an intermolecular, enantioselective three-component radical vicinal dicarbofunctionalization reaction of olefins enabled by merger of radical addition and cross-coupling using photoredox and copper dual catalysis. Key to the success of this protocol relies on chemoselective addition of acyl and cyanoalkyl radicals, generated in situ from the redox-active oxime esters by a photocatalytic N-centered iminyl radical-triggered C-C bond cleavage event, onto the alkenes to form new carbon radicals. Single electron metalation of such newly formed carbon radicals to TMSCN-derived L1 Cu(II)(CN) 2 complex leads to asymmetric cross-coupling. This three-component process proceeds under mild conditions, and tolerates a diverse range of functionalities and synthetic handles, leading to valuable optically active β –cyano ketones and alkyldinitriles, respectively, in a highly enantioselective manner (>60 examples, up to 97% ee). Vicinal dicarbofunctionalization (DCF) reactions of alkenes have been extensively explored in ionic chemistry but the enantioselective radical mediated version of DCF remains largely unexplored. Here, the authors demonstrate a radical vicinal DCF reaction of olefins by merging of radical addition and cross-coupling using photoredox and copper dual catalysis.