Photoredox-Catalyzed Intramolecular Aminodifluoromethylation of Unactivated Alkenes

Abstract

A photoredox catalyzed aminodifluoromethylation of unactivated alkenes has been developed in which HCF2SO2Cl is used as the HCF2 radical source. Sulfonamides were active nucleophiles in the final step of a tandem addition/oxidation/cyclization process to form pyrrolidines, and esters were found to cyclize to form lactones. Thus, a variety of pyrrolidines and lactones were obtained in moderate to excellent yield. In order for the cyclization reactions to be efficient, a combination of a copper catalyst (Cu(dap)2Cl) and silver carbonate was crucial to suppressing a competing chloro, difluoroalkylation process.

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

“…of NaHCO 3 as a base to neutralize the equivalent of HCl generated during the reaction based on our initial hypothesis, and we were encouraged to observe a significant increase in product yield (up to 91%) and with good enantioselectivity (82% ee) and found that no hydroamination byproduct was observed (entry 2). A thorough evaluation of different inorganic salts indicated that they have significant impact on the efficiency and enantioselectivity; and Ag 2 CO 3 was found to be particularly effective (entries 2–7)37. Noteworthy is that Ag 2 CO 3 was used to improve the product yield of the intramolecular aminofluoroalkylation reaction in racemic form under photoredox catalysis37.…”

“…A thorough evaluation of different inorganic salts indicated that they have significant impact on the efficiency and enantioselectivity; and Ag 2 CO 3 was found to be particularly effective (entries 2–7)37. Noteworthy is that Ag 2 CO 3 was used to improve the product yield of the intramolecular aminofluoroalkylation reaction in racemic form under photoredox catalysis37. Its good performance compared with other inorganic bases might be due to the generation of the highly insoluble AgCl and weaker carbonic acid to ensure unselective background reactivity is minimal.…”

“…Within the burgeoning field of radical fluoroalkyl reagents21222324252627, great progress has been made in the direct 1,2-difunctionalization-type fluoroalkylation of alkenes by employing stable fluoroalkylsulfonyl chlorides as the radical sources to in situ generate the desired fluoroalkyl radicals3536373839. For the efficient collection of fundamental yet synthetically formidable chiral β-fluoroalkyl amine-building blocks directly from readily available materials and particularly intrigued by our recent success in asymmetric radical aminotrifluoromethylation of alkenes using a dual-catalytic system of Cu(I) and CPA34, we envisaged the possibility of realizing an unprecedented asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes with various fluoroalkylsulfonyl chlorides through such a dual-catalytic system (Fig.…”

“…Several challenges are associated with the development of this reaction, such as (1) stoichiometric amount of strong achiral Brønsted acid HCl would be generated, which might not only result in strong background reactions against the chiral acid-catalysed process but also lead to competitive hydroamination of alkene as previous report40; (2) it is not easy to search for a uniform catalytic system broadly applicable to a variety of electronically distinct fluoroalkylsulfonyl chlorides, such as perfluoroalkyl, trifluoromethyl, difluoroacetyl and even difluoromethyl radical precursors. Most notable is that difluoromethylsulfonyl chloride is only used as the suitable radical source for the intramolecular aminofluoroalkylation reaction in racemic form under photoredox catalysis37. Herein we describe our efforts toward the development of the dual Cu(I)/CPA-catalysed asymmetric radical intramolecular aminofluoroalkylation of alkenes with various fluoroalkylsulfonyl chlorides.…”

Recent advances in dual transition metal–visible light photoredox catalysis

“…The reaction involves a C-N bond forming step which is the result of the interaction of the unsaturated C=C bond and the difluoromethyl radical generated from HCF 2 SO 2 Cl by copper based Cu(dap) 2 Cl photocatalyst and visible light (Figure 10). 41 Alkenes (26), having tosylated terminal amino-function are converted into 2-difluoroethyl-pyrrolidines (28), except those bearing better nucleophiles, such as carboxylate-substituents which afforded the corresponding lactones.…”