20 Years of Forging N-Heterocycles from Acrylamides through Domino/Cascade Reactions

Abstract

Acrylamides are versatile building blocks easily obtained from readily available starting materials. During the last 20 years, these valuable substrates bearing a nucleophilic nitrogen atom and an electrophilic double bond have proved to be efficient domino partners leading to a wide variety of complex aza-heterocycles of synthetic relevance. In this non-exhaustive review, metal free and metal triggered reactions followed by an annulation will be presented, these two approaches allowing a good modulation of the reactivity of the polyvalent acrylamides.

Visible-Light-Promoted Radical Cascade Cyclization of 2-Vinyl Benzimidazoles: Access to Benzo[4,5]imidazo[1,2-b]isoquinolin- 11(6H)-ones

“…In this context, it is crucial for its success to rationally design radical acceptors. To this end, N- acrylamides, N- cyanamides, pendent olefins, and nitriles have been well developed, allowing diversity-oriented synthesis of numerous potentially bioactive compounds. Given the significance of benzimidazole-based heterocyclic systems, our interest in heterocycle construction and radical chemistry prompted us to create a novel radical acceptor, N -aroyl 2-vinyl benzimidazole, for radical cascade cyclization.…”

Organocatalytic cascade nucleophilic/aza-Michael addition reactions: metal-free catalytic strategy for the synthesis of hydantoins

“…Organocatalytic aza-nucleophilic addition triggered cascade reactions have attracted considerable attention in the past few years and provide a reliable tool for the synthesis of nitrogen-containing heterocycles. 22 In the case of N -alkoxy acrylamides, the nucleophilicity of the amide nitrogen atom was enhanced by α-effect, which is beneficial for the first step of nucleophilic attack. On the one hand, N -alkoxy acrylamides (R = H, alkyl or aryl groups) are preferable to function as 1,4- N , C β -synthon to furnish [4 + 2] annulation reactions.…”

Lewis base-catalyzed cascade [4 + 2]-annulation reaction of N-alkoxy acrylamides and acyl isothiocyanates: facile access to 2-imino-1,3-thiazinone derivatives

“…In the past decades, acrylamides have emerged as versatile building blocks for the construction of various functionalized nitrogen-containing heterocycles. 15 The use of N -alkoxy acrylamides in Lewis base-catalyzed aza-nucleophilic addition to trigger cascade annulation reactions has been explored in great detail. In these reactions, N -alkoxy acrylamide acts as a 1,4- N , C β -synthon or a 1,3- N , C α -synthon.…”