Copper‐Catalyzed Enantioselective C(sp3)−SCF3 Coupling of Carbon‐Centered Benzyl Radicals with (Me4N)SCF3

• Published in: Angewandte Chemie International Edition Vol. 63; no. 11; pp. e202319850 - n/a
• Main Authors: Zhang, Wei, Tian, Yu, Liu, Xiao‐Dong, Luan, Cheng, Liu, Ji‐Ren, Gu, Qiang‐Shuai, Li, Zhong‐Liang, Liu, Xin‐Yuan
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 11.03.2024; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkenes; benzyl halides; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Copper; copper catalysis; Cross coupling; Enantiomers; Halides; Physical Sciences; radical reaction; Radicals; Reagents; Science & Technology; Steric effects; HALIDES; REAGENTS; radical reaction; REACTIVITY; benzyl halides; alkenes; BROMIDES; NUCLEOPHILIC TRIFLUOROMETHYLTHIOLATION; MILD; copper catalysis; ARYL BORONIC ACIDS; ROLES; cross-coupling; DERIVATIVES; ACCESS
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202319850

In contrast with the well‐established C(sp2)−SCF3 cross‐coupling to forge the Ar−SCF3 bond, the corresponding enantioselective coupling of readily available alkyl electrophiles to forge chiral C(sp3)−SCF3 bond has remained largely unexplored. We herein disclose a copper‐catalyzed enantioselective radical C(sp3)−SCF3 coupling of a range of secondary/tertiary benzyl radicals with the easily available (Me4N)SCF3 reagent. The key to the success lies in the utilization of chiral phosphino‐oxazoline‐derived anionic N,N,P‐ligands through tuning electronic and steric effects for the simultaneous control of the reaction initiation and enantioselectivity. This strategy can successfully realize two types of asymmetric radical reactions, including enantioconvergent C(sp3)−SCF3 cross‐coupling of racemic benzyl halides and three‐component 1,2‐carbotrifluoromethylthiolation of arylated alkenes under mild reaction conditions. It therefore provides a highly flexible platform for the rapid assembly of an array of enantioenriched SCF3‐containing molecules of interest in organic synthesis and medicinal chemistry. A copper‐catalyzed enantioselective radical C(sp3)−SCF3 coupling of secondary/tertiary benzyl radicals with the easily available (Me4N)SCF3 reagent was developed to afford enantioenriched trifluoromethylthiolated molecules. The key to the success lies in the utilization of chiral phosphino‐oxazoline‐derived anionic N,N,P‐ligands for the reaction initiation and enantioselectivity.