Synthesis of α-Amidoketones through the Cascade Reaction of Carboxylic Acids with Vinyl Azides under Catalyst-Free Conditions

Abstract

An efficient synthesis of α-amidoketone derivatives through the cascade reactions of carboxylic acids with vinyl azides is presented. Compared with literature protocols, notable features of this new method include catalyst-free conditions, broad substrate scope, good tolerance of a wide range of functional groups, and high efficiency. In addition, the synthetic potential of this method as a tool for late-stage modification was convincingly manifested by its application in the structural elaborations of a number of carboxylic acid drug molecules.

Vinyl azides in organic synthesis: an overview

“…This strategy led to the formation of diverse α-amido ketones in fair to very good yields (58–88%). 85 α-Amido ketone derivatives have attracted attention due to their being not only necessary motifs of a plethora of pharmaceutically active compounds but also essential intermediates that are broadly utilized in organic synthesis. 86…”

“…Eventually, the unstable aziridine 284 through a thermal rearrangement produced α-amido ketone 283 (Scheme 79). 85…”

“…Eventually, the unstable aziridine 284 through a thermal rearrangement produced a-amido ketone 283 (Scheme 79). 85 In 2017, Yu et al synthesized b-keto phosphine oxides 286 through Mn(III)-catalyzed phosphorylation of vinyl azides 1 in fair to excellent yields (65-92%). 87 Organophosphorus compounds play an important role in material science, organic chemistry, and pharmaceuticals.…”

Metal-Controlled Switchable Regioselective Synthesis of Substituted Imidazoles and Pyrroles via Ring Opening/Cyclocondensation with 2H-Azirines

“…Due to the significant inherent ring strain (Scheme 2), 17 2Hazirines 18 or its equivalents 19 have been successfully used as carbon and nitrogen precursors. 20 we endeavor to develop disparate transformations by adjusting reaction parameters.…”

“…Due to the significant inherent ring strain (Scheme ), 2 H -azirines or its equivalents have been successfully used as carbon and nitrogen precursors . Tandem C–C/N–C cleavage of 2 H -azirines followed by intermolecular cyclization or rearrangement accessed nitrogen-containing heterocyclic architectures.…”