Carboamination of Unactivated Alkenes through Three‐Component Radical Conjugate Addition

Abstract

Two‐component Giese type radical additions are highly practical and established reactions. Herein, three‐component radical conjugate additions of unactivated alkenes to Michael acceptors are reported. Amidyl radicals, oxidatively generated from α‐amido oxy acids using redox catalysis, act as the third reaction component which add to the unactivated alkenes. The adduct radicals engage in Giese type additions to Michael acceptors to provide, after reduction, the three‐component products in an overall alkene carboamination reaction. Transformations which can be conducted under practical mild conditions feature high functional group tolerance and broad substrate scope.

Intermolecular radical carboamination of alkenes

“…Sequential fragmentation of 47 with the extrusion of CO 2 and acetone generates the amidyl radical 48, which then adds to the carbon-carbon double bond of the alkene to provide the adduct radical 49. EBX reagent traps the C-radical 49 to give alkene 64 Commonly used N-protecting groups installed at the starting a-amido-oxy acids were tolerated and the corresponding carboamination products were obtained in satisfactory yields (51a-h). N-Methyl a-amido-oxy acids bearing electron deficient protecting groups (Troc or Tfoc) also worked well as N-radical precursors in this transformation (51i, 51j).…”

Bromine as a Visible-Light-Mediated Polarity-Reversal Catalyst for the Functionalization of Aldehydes

“…Multi-component radical cascade reactions play a privileged role in organic synthesis and enable direct construction of complex and diverse molecular scaffolds. 7,[43][44] The failure of hydroacylation with acrylates 4 and the radical nature of this PRC led us to search for a possible bromine-catalyzed threecomponent coupling reaction. We speculated that the bromine-induced nucleophilic acyl radicals from aldehydes would preferentially add to electron-de cient acylates in the presence of vinyl arenes.…”

Exploiting Imine Photochemistry for Masked N‐Centered Radical Reactivity

“…Nitrogen‐centered radicals have drawn a great deal of interest in recent years, largely driven by photochemical innovation . Prominent alternatives to amine radical cations include amidyl or imidyl radicals arising from oxidation of N−H bonds via proton‐coupled electron transfer (PCET) or from N−X bonds via homolysis, reduction, or even oxidation by employing α‐aminoxy carboxylic acid auxiliaries popularized by the groups of Leonori and Studer . Alternatively, it was hypothesized that initiation of our desired fragmentation‐cyclization sequence could be accomplished not from a discrete N‐centered radical but a temporaneous N‐centered radical.…”

“…[24,25] Prominent alternatives to amine radical cations include amidyl or imidyl radicals arising from oxidation of N À Hbonds [26,27] via proton-coupled electron transfer (PCET) [28] or from NÀXb onds via homolysis, [29][30][31] reduction, [32] or even oxidation [33] by employing a-aminoxy carboxylic acid auxiliaries popularized by the groups of Leonori [34,35] and Studer. [36,37] Alternatively,i tw as hypothesized that initiation of our desired fragmentation-cyclization sequence could be accomplished not from a discrete N-centered radical but a temporaneous N-centered radical. More specifically,acyclopropylimine would serve as am asked N-centered radical, revealing the nitrogen-based radical character only upon excitation.…”