Copper-Catalyzed Hydrogen Atom Transfer and Aryl Migration Strategy for the Arylalkylation of Activated Alkenes

Abstract

Herein, we describe the copper-catalyzed arylalkylation of activated alkenes via hydrogen-atom transfer and aryl migration strategy. The reaction was carried out through a radical-mediated continuous migration pathway using N-fluorosulfonamides as the alkyl source. The primary, secondary, and tertiary alkyl radicals formed by intramolecular hydrogen-atom transfer proceeded smoothly. This methodology is an efficient approach for the synthesis of various amide derivatives possessing a quaternary carbon center with good yields and high regioselectivity.

Copper‐Catalyzed Fluoroamide‐Directed Remote C(sp3)‐H Bond Functionalization Through Intramolecular Hydrogen Atom Transfer

“…Recently, the strategy of copper-catalyzed fluoroamide-directed remote CÀ H functionalization has also been successfully applied in the difunctionalization of some types of alkenes, serving as an elegant and robust method to convert easily accessible alkenes into various functionalized molecules. [43,[45][46] In 2022, Li and co-workers developed a copper-catalyzed remote benzylic CÀ H functionalization enabling 1,2-difunctionalization of alkenes with o-methylbenzenesulfamides and nucleophiles, including alcohols, indoles, pyrroles, and the intrinsic amino groups. [43] A broad range of N-fluoro-o-alkylbenzenesulfamides 1, (hetero)aryl alkenes 29, and nucleophiles participated in this transformation to furnish corresponding functionalized dialkyl ethers, 3-alkylindoles, and 3-alkylpyrroles redox-neutral conditions, a wide substrate scope, and broad applications in the late-stage modification of bioactive molecules.…”

“…In the same year, the Liu and Liang group disclosed a copper-catalyzed HAT and aryl migration method for the arylalkylation of activated alkenes. [46] The reactions between aliphatic N-fluorosulfonamides 5 and N-(arylsulfonyl)acrylamides 154 under the catalysis of Cu(Phen)Cl 2 afforded corresponding alkene arylalkylated products 155 in moderate to good yields (Scheme 58). A variety of N-acrylamide derivatives smoothly participated in the transformation under mild conditions.…”

Recent Advances in the Functionalization of Remote C−H Bonds by Hofmann‐Löffler‐Freytag‐type Reactions

“…This reaction can significantly expand the scope of metal-free HLF reactions and provides a convenient strategy for C(sp In 2022, Liang et al developed a strategy for the copper-catalyzed arylalkylation of activated alkenes via HAT and aryl migration (Scheme 43). [47] The reaction uses N-fluorosulfonamides 199 as the alkyl source and proceeds via a radical-mediated sequential migration pathway. This method is effective for the synthesis of various amide derivatives with quaternary carbon centers with good yield and high regioselectivity.…”

Visible-Light-Photocatalyzed Dicarbofunctionalization of Conjugated Alkenes with Ketone-Based Dihydroquinazolinones

“…3 Such transformation involves tandem trifluoromethylation/aryl migration/desulfonylation events in a unified single operation, which encases the advent of an aryl transfer, 4 as well as desulfonylation tactics. 5 Since then, radical dicarbofunctionalization of N-aryl-N-(arylsulfonyl)acrylamides, including arylalkylation and diarylation, has been substantially spurred to enable the rapid construction of sterically congested all-carbon quaternary α-stereocenters, which is, indeed, a formidable task. 6 In this paradigm, the majority of radical dicarbofunctionalizations entail either electrophilic alkyl radical sources 6a −d,f,k,l or nucleophilic alkyl radical precursors 6e,h−j combined with an external sacrificial oxidant (di-tert-butyl peroxide, perdisulfate, etc.).…”