Radical α,β-Dehydrogenation of Saturated Amides via α-Oxidation with TEMPO under Transition Metal-Free Conditions

Abstract

A transition metal-free radical process for the selective α,β-dehydrogenation of saturated amides under mild conditions is developed. Utilizing radical activation strategy, the challenging issue associated with the low α-acidity of amides is resolved. For the first time, α,β-unsaturated Weinreb amides and acrylamides could be efficiently prepared directly from corresponding saturated amides. Mechanistic studies confirm the radical nature of this transformation. Two gram scale α,β-dehydrogenation have also been performed to demonstrate the utility of this method.

Transition‐Metal‐Free Multiple Functionalization of Piperidines to 4‐Substituted and 3,4‐Disubstituted 2‐Piperidinones

“…Although it seems reasonable that the third C−H oxidation step occurs through a radical process, as depicted in Scheme ( I → M → N ), a base‐mediated anionic elimination process is a possibility that needed to be reviewed . Accordingly, a radical‐clock experiment was designed.…”

Synthesis and odor characteristics of N‐substituted pyrrolyl ketones derived from N‐substituted acetylpyrroles and alcohols

“…Radical anion B is a pyrrolylacetyl radical, which might be converted into the corresponding pyrrolyl ketone D by single electron transfer to release radical anion C. In addition, the elimination of pyrrolyl ketone D would lead to the formation of pyrrolyl chalcone E under the basic conditions, which was observed by GC-MS in the process of the reaction and isolated in a 20% yield. Subsequently, the enone intermediate is reduced to generate radical anion F via single electron transfer [32]. Radical anion F reacts with benzyl alcohol to afford the product propyl 1-methylpyrrolyl ketone 3a, along with the generation of radical anion A.…”

Photoinduced Desaturation of Amides by Palladium Catalysis

“…In addition, they also serve as versatile building blocks to prepare complex nitrogen-containing molecules . Among various methods known to prepare α,β-unsaturated amides, direct desaturation of amides represents a straightforward approach. , Conventional approaches involve installation of a leaving group at the amide α position, followed by an elimination process, which generally require multiple steps . Recently, Newhouse has developed a suite of catalytic dehydrogenation methods with esters, amides, nitriles, ketones, and carboxylic acids through in situ generation of the corresponding enolate, followed by transmetalation and β-hydrogen elimination (Scheme a) .…”