Unlock the C–N Bond Amidation of Enaminones: Metal-Free Synthesis of Enamides by Water-Assisted Transamidation

Abstract

The C−N bond transamidation of primary amides with N,N-dimethyl enaminones has been efficiently realized by heating in the presence of trifluoromethanesulfonic acid (TfOH). The method enables the practical synthesis of valuable enamides without the use of any metal reagent. In addition, this transamidation protocol can also be expanded to the reactions of sulfonamides, and the late-stage functionalization on sulfonamide drugs such as Celecoxib and Valdecoxib has been verified. Moreover, the participation of water in assisting the transamidation process has been identified by the isotope labeling experiments using D 2 O, disclosing a new possibility in designing catalytic tactic to other transamidation reactions.

Metal-free efficient synthesis of aryl sulfonamides from N-hydroxy sulfonamide and amines

“…7 Along with sulfonyl chloride, various sulfur analogues such as sulfonyl hydrazides, azides, sulfinates, thiols and enaminones were exploited as reaction partners of amines to produce sulfonamides. 8…”

Rhodium(III)-Catalyzed Coupling of Quinolin-8-carboxaldehydes with CF3–Imidoyl Sulfoxonium Ylides by Chelation-Assisted C(sp2)-H Bond Activation for the Synthesis of Trifluoromethyl-Substituted Enaminones

“…The traditional routes to enaminones lie in the condensation between the 1,3-dicarbonyl compounds and amines or the Michael addition of α,β-ynones/allenic ketones with amines or ring-opening of heterocycles, in which the two isomeric enaminones could be usually generated or the presynthesis of substrates was inevitable. In recent years, other miscellaneous strategies for the synthesis of enaminone scaffolds have been reported, including rhodium-catalyzed denitrogenative rearrangement of 1-( N -sulfonyl-1,2,3-triazol-4-yl)­alkanols, three-component coupling reactions of terminal alkynes, α-diazoketones, and arylamines, copper-catalyzed coupling of ketones and aromatic nitriles, decarboxylative coupling of α-keto acids with oxime acetates or vinyl azides or cyclic amines, amides-involved transformations to enaminones, and so on. Despite numerous elegant approaches concerning enaminone synthesis have been attained, the development of more efficient methods to build specifically functionalized enaminones from readily available materials is still highly desired.…”