Polarity-Mismatched Addition of Electrophilic Carbon Radicals to an Electron-Deficient Acceptor: Cascade Radical Addition–Cyclization–Trapping Reaction

Abstract

The polarity-mismatched perfluoroalkyl radical addition to electron-deficient alkenes was studied. For this study, several substrates having two polarity-different radical acceptors were employed to investigate the regiochemical courses of cascade reaction. In the case of substrate 1 having a methacryloyl moiety, we found polarity-mismatched perfluoroalkylation giving 15a-e as a major course over the polarity-matched perfluoroalkylation giving 16a-e. Moreover, in the case of substrates 2-7, perfluoroalkyl radicals selectively added to an electron-deficient alkene moiety of 2-7, to give polarity-mismatched perfluoroalkylation products without the formation of regioisomers. Next, the control of enantioselectivity was studied. In the case of substrates 1 and 3, the reaction proceeded with good enantioselectivities by employing a chiral Lewis acid, prepared from chiral box ligand 24 and Zn(OTf)(2). For direct comparison, we also studied the reaction with other carbon radicals, derived from ICH(2)CO(2)Et, ICH(2)CN, BrC(CO(2)Et)(2)Me, and CCl(3)Br, which have electrophilic character.

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

“…In contrast to the great success in developing nucleophilic and electrophilic fluoroalkylation reactions, the corresponding asymmetric radical fluoroalkylation versions remain scarce171819, largely because of the intrinsic reactivity of the involved odd-electron species20. On the other hand, intermolecular addition of fluoroalkyl radicals to unactivated alkenes has emerged as one of the most attractive strategies for the direct 1,2-difunctionalization of alkenes to simultaneously construct two vicinal chemical bonds by using a variety of radical fluoroalkyl precursors in racemic form21222324252627.…”

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

“…Particularly, the substrate 16 having a phenyl group gave the intermediate linear π-radical. Thus, the capture of linear vinyl radical with atom-transfer reagent would be influenced by the steric hindrance around the quaternary carbon atom [43]. …”

“…These approaches can be classified into two categories according to their reaction mechanism (Fig. 1) [37–43]. …”

“…We have also investigated a new type of chiral Lewis acid mediated cyclization approach for cascade bond-forming reactions via sequential radical–radical processes (Fig. 2) [39–43]. In these studies, the control of the enantioselectivities was achieved by the introduction of a hydroxamate ester as a two-point-binding coordination tether into the middle of substrates A , together with the control of the rotamer population of substrates [39,42].…”

Progress in Enantioselective Radical Cyclizations

“…Thus, increasing the amount of Et 3 B to 20 equivalents improved the enantioselectivity to give 85 % ee of 29 , because the slow trapping reaction of the intermediate radical with Et 3 B allows the reversibility, leading to a decrease in the enantioselectivity. Miyabe's group has studied enantioselective cascade reactions with perfluoroalkyl radicals based on this strategy ,…”