Catalyst-Free, Metal-Free, and Chemoselective Transamidation of Activated Secondary Amides

Abstract

A simple protocol, which is catalyst-free, metal-free, and chemoselective, for transamidation of activated secondary amides in ethanol as solvent under mild conditions is reported. A wide range of amines, amino acids, amino alcohols, and the substituents, which are problematic in catalyzed transamidation, are tolerated in this methodology. The transamidation reaction was successfully extended to water as the medium as well. The present methodology appears to be better than the other catalyzed transamidations reported recently.

Light-Driven Reductive Cleavage of Sulfonamides Promoted by Thiourea Organophotosensitizers

“…According to the representative procedure, starting from N-benzyl-4-methylbenzene-1-sulfonamide (4r, 1 equiv, 150 mg, 0.57 mmol) and 4-methoxybenzoyl chloride (1.5 equiv, 0.12 mL, 0.86 mmol); flash chromatography on silica gel (EtOAc/Cy, 1:9) gave compound 4n (182 mg, 0.46 mmol, 80%) as a white solid. 1 47 Synthesis of Compound 4o. A round-bottomed flask containing N-benzyl-4-methylbenzene-1-sulfonamide (4r, 1 equiv, 150 mg, 0.57 mmol), and DMAP (0.1 equiv, 7 mg, 0.057 mmol), dissolved in THF (5 mL), was cooled to 0 °C.…”

Chemoselective Cleavage of Acylsulfonamides and Sulfonamides by Aluminum Halides

“…From N-benzyl-N-tosylpivalamide (4ae, 0.345 g, 1 mmol) following general procedure A; yield: 0.226 g (86%). 1 Acylsulfonamide (4). General procedure B.…”

“…N-deacylation and dealkylation are important manipulations for deprotecting sulfonamides. Secondary acylsulfonamides are inert to nucleophilic attack under acidic and basic conditions, and an activation by N-alkylation is required to facilitate deacylation by alcohol or amine nucleophiles. This strategy, after attaching a solubility-modifying group to either the sulfonyl or acyl end, has been widely applied in solid-phase peptide synthesis (Scheme A) .…”

Structure and Additive-free Transamidation of Planar N-Cyano Amides

“…The reactions of activated tertiary amides include transamidation in the presence of transition metal, 4,14−18 base, 19−21 or other reactions such as hydrolysis or alcoholysis, 22,23 but transamidation in the absence of additives is rare. 10,24,25 Moreover, most activated amides have nonplanar structures.…”

“…We hypothesize that the linear geometry of the cyano group would expand the substrate scope 25 and bypass the need for the harsh reaction conditions employed in the literature. 24 In addition, the structure and reactivity of N-cyano amide are of interest since the reaction of an N-cyano compound with a nucleophile at the cyano carbon has been reported. 34 Herein, we describe the structures and trans amidation reaction of N-cyano amides.…”