α-Amino Radical-Mediated Diverse Difunctionalization of Alkenes: Construction of C–C, C–N, and C–S Bonds

Abstract

A general catalytic methodology for 1,2-RF/Y-difunctionalization of conjugated alkenes is reported. Diverse functionalized carbon radicals (RF•), which are generated through copper­(I)-initiated selective halogen atom abstraction via a tert-butyl hydroperoxide-induced α-amino radical process, undergo regiocontrolled addition to carbon–carbon double bonds. The newly formed carbon radicals combine with Y = CN, N3, or NCS from TMSY in a copper­(I)-promoted process to form a broad spectrum of α-cyano-, α-azido-, and α-thiocyano-β-substituted products with additional functionalities in RF in high yields. Conversion of the reaction products to functionalized cyclopropane, amide, amine, triazole, thiol, and tetrazole highlights the potential utility of this method.

Precise Introduction of the −CHnX3–n (X = F, Cl, Br, I) Moiety to Target Molecules by a Radical Strategy: A Theoretical and Experimental Study

“…To verify the prediction in the map of radicals, the reported relevant reactions are collected in Figure (a) for comparison. The α-aminoalkyl radicals were found to abstract Cl, Br, and I atoms selectively. − The aryl radical, methyl radical, and ethyl radicals have been reported to abstract H atoms. ,,, These experimental atom transfer agents meet the specific HAT and XAT reaction criteria in Figures S13 and S14. Besides, our computations predict the selective abstraction of Br and I atoms from CH 2 Br 2 and CH 2 I 2 , respectively, by an α-aminoalkyl radical, which is verified by the experiments in Figure (b).…”

“…The • CHCl 2 radical that is formed in this way was shown by Doyle and co-workers to add regioselectively to the carbon−carbon double bond of styrene (see Scheme 1(b)). 25,26 This process is also suitable for halogen atom abstraction of methyl halides such as CHBr 3 , CHI 3 , or CHBrCl 2 to form diverse α-peroxy-β-substituted ethylbenzene products.…”

Merging Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Suzuki–Miyaura-Type Cross-Coupling of Alkyl Iodides and Organoborons

“…This blueprint for radical generation can be exploited in different settings, which include the coupling of alkyl iodides with N-nucleophiles to assemble S N 2-elusive C(sp 3 )–N bonds. 13 This reactivity paradigm is possible by merging XAT with copper catalysis so that an alkyl radical is generated and then captured by a copper-bound N fragment.…”

Application of α-Aminoalkyl Radicals as Reaction Activators

“…Subsequently, Doyle and co-workers extended their aminoalkyl-radical-mediated XAT strategy to the diverse difunctionalization of conjugated alkenes (Scheme 6). 25 The combination of a copper catalyst, an amine, TBHP, organic halides and TMS-Y (Y = CN, N 3 or NCS) realized the carbocyanation, carboazidation and carbothiocyanation of styrene derivatives. A broad spectrum of -cyano-, -azido-and -thiocyano--substituted products with additional functionalities on R 2 were synthesized in good to high yields.…”