Ketenimines Generated from Ynamides: Versatile Building Blocks for Nitrogen‐Containing Scaffolds

Abstract

Using ynamides as readily available starting materials, a single step can generate highly reactive ketenimines, which can then undergo a variety of transformations. The choice of the method for generating the ketenimine dictates the outcome of the reaction that can, moreover, be precisely steered through minor variations of the starting material. This Concept gives an overview of the different existing methodologies for this objective, showcasing the diverse nitrogen-containing frameworks that can be obtained by this highly versatile strategy.

Ynamides in Free Radical Reactions

“…Then, an intramolecular addition onto the ynamide occurs, via a 5-exo-dig cyclization, generating vinyl radical 6. This is followed by 6-endo-trig cyclization with the pendant aromatic ring (7). Rearomatization occurs through a hydrogen abstraction from the tin hydride to regenerate the tin radical species.…”

“…In particular, the activation of ynamides by electrophilic reagents to generate a key keteniminium intermediate has been the subject of numerous studies. [5] Other modes of reaction, such as their anionic chemistry [6] or the in situ formation of ketenimines, [7] as well as specific types of reactions, in particular cyclizations and cycloadditions, [8][9][10][11][12] have also been exploited and recently covered in several reviews and highlights. Nevertheless, despite the myriad of synthetic opportunities conceivable, the use of ynamides in free radical reactions, notably as radical acceptors (Scheme 1, right), has remained relatively underexplored.…”

“…In particular, the activation of ynamides by electrophilic reagents to generate a key keteniminium intermediate has been the subject of numerous studies [5] . Other modes of reaction, such as their anionic chemistry [6] or the in situ formation of ketenimines, [7] as well as specific types of reactions, in particular cyclizations and cycloadditions, [8–12] have also been exploited and recently covered in several reviews and highlights.…”

Skeletal reorganization divergence of N-sulfonyl ynamides

“…Ynamides are a type of N-substituted electron-rich alkynes that exhibit unique chemical properties and serve as versatile synthons in organic synthesis [33][34][35][36][37][38][39][40][41][42] . For example, ynamides could act as flexible cyclization partners in heterocycle synthesis [43][44][45] , carbene precursors [46][47][48][49] and enamide precursors 50,51 , racemization-free coupling reagents for peptide and macrolide synthesis [52][53][54] and C2 building blocks of multicomponent reactions) [55][56][57] .…”

Skeletal Reorganization Divergence of N-Sulfonyl Ynamides

“…Therefore, it would be interesting to explore a distinct and efficient approach to functionalized thiete sulfones. Ynamides are type of N-substituted electron rich alkynes which exhibit unique chemical properties and serve as versatile synthons in organic synthesis [33][34][35][36][37][38][39][40][41][42] . For example, ynamides could act as flexible cyclization partners in heterocycle synthesis [43][44][45] , carbene precursors [46][47][48][49] and enamides precursors [50][51] , racemization-free coupling reagents for peptide and macrolide synthesis [52][53][54] , C2 building blocks of multicomponent reactions (MCRs) [55][56][57] .…”