Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

• Published in: Nature communications Vol. 8; no. 1; p. 14841
• Main Authors: Lin, Jin-Shun, Wang, Fu-Li, Dong, Xiao-Yang, He, Wei-Wei, Yuan, Yue, Chen, Su, Liu, Xin-Yuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-03-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 639/638/403/933; 639/638/549/972; 639/638/77/883; Acids; Humanities and Social Sciences; multidisciplinary; Science; Science (multidisciplinary); Success; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14841

Although great success has been achieved in asymmetric fluoroalkylation reactions via nucleophilic or electrophilic processes, the development of asymmetric radical versions of this type of reactions remains a formidable challenge because of the involvement of highly reactive radical species. Here we report a catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes with commercially available fluoroalkylsulfonyl chlorides as the radical sources, providing a versatile platform to access four types of enantioenriched α-tertiary pyrrolidines bearing β-perfluorobutanyl, trifluoromethyl, difluoroacetyl and even difluoromethyl groups in excellent yields and with excellent enantioselectivity. The key to success is not only the introduction of the CuBr/chiral phosphoric acid dual-catalytic system but also the use of silver carbonate to suppress strong background and side hydroamination reactions caused by a stoichiometric amount of the
in situ
generated HCl. Broad substrate scope, excellent functional group tolerance and versatile functionalization of the products make this approach very practical and attractive.
Methods for the asymmetric introduction of organofluorine groups are often limited by the lack of variability in the starting materials. Here the authors report an asymmetric radical process for the introduction of fluoroalkyl groups using readily available fluoroalkylated sulfonyl chlorides.