Enantioselective CH Bond Functionalization Triggered by Radical Trifluoromethylation of Unactivated Alkene

• Published in: Angewandte Chemie (International ed.) Vol. 53; no. 44; pp. 11890 - 11894
• Main Authors: Yu, Peng, Lin, Jin-Shun, Li, Lei, Zheng, Sheng-Cai, Xiong, Ya-Ping, Zhao, Li-Jiao, Tan, Bin, Liu, Xin-Yuan
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 27.10.2014; WILEY‐VCH Verlag; Wiley
• Subjects: Activation; Activation analysis; Alkenes; Asymmetry; Bonding; Catalysis; Chemistry; Chemistry, Multidisciplinary; copper; CH activation; enantioselectivity; Olefins; Physical Sciences; radical chemistry; Radicals; reaction mechanisms; Science & Technology; Stereoselectivity; enantioselectivity; ACTIVATION; DESIGN; ASYMMETRIC-SYNTHESIS; HYDROGENATION; REAGENTS; IMINES; reaction mechanisms; ATOM; ETHERS; C-H activation; COPPER-CATALYZED TRIFLUOROMETHYLATION; copper; DERIVATIVES; radical chemistry; CH activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201405401

An asymmetric unactivated alkene/CH bond difunctionalization reaction for the concomitant construction of CCF3 and CO bonds was realized by using a Cu/Brønsted acid cooperative catalytic system, thus providing facile access to valuable chiral CF3‐containing N,O‐aminals with excellent regio‐, chemo‐, and enantioselectivity. Mechanistic studies revealed that this reaction may proceed by an unprecedented 1,5‐hydride shift involving activation of unactivated alkenes and a radical trifluoromethylation to initiate subsequent enantioselective functionalization of CH bonds. Control experiments also suggested that chiral Brønsted acid plays multiple roles and not only controls the stereoselectivity but also increases the reaction rate through activation of Togni’s reagent. En route: The title redox‐neutral reaction provides a convenient route to valuable enantioenriched trifluoromethylated N,O‐aminals in good to excellent yields and with excellent regio‐, chemo‐, and enantioselectivity. The reaction features a CuI/Brønsted acid system and broad substrate scope.