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. 2017 Mar 23:8:14841.
doi: 10.1038/ncomms14841.

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

Jin-Shun Lin  1 , Fu-Li Wang  1 , Xiao-Yang Dong  1 , Wei-Wei He  1 , Yue Yuan  1 , Su Chen  1 , Xin-Yuan Liu  1
Affiliations

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

Jin-Shun Lin et al. Nat Commun. .

Abstract

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.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Our proposal.
Dual Cu(I)/CPA-catalysed asymmetric radical aminofluoroalkylation of alkenes.
Figure 2
Figure 2. Versatile transformations.
(a,b) Reduction and hydrolysis reaction. (c) Cyclization reaction. (d) Reduction to a difluoro-containing pyrrolizidine. KHMDS, Potassium bis(trimethylsilyl)amide; PIFA, [Bis(trifluoroacetoxy)iodo]benzene.
Figure 3
Figure 3. Mechanistic study.
(a) Trapping with TEMPO. (b) Radical clock. (c,d) Control reactions. TEMPO, 2,2,6,6-tetramethyl-1-piperidinyloxy.
Figure 4
Figure 4. Mechanistic proposal.
Two pathways were tentatively proposed.
See this image and copyright information in PMC

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