Trimethylaluminium‐Mediated Reaction of Primary Carboxamides with Amines and Indoles: A Convenient Synthesis of Amidines and Indole‐3‐acylimines

Abstract

A simple, convenient and general method, exhibiting good functional group tolerance, is described for the synthesis of N‐ and N,N‐disubstituted amidines by the reaction of primary carboxamides with amines mediated by trimethylaluminium (AlMe3). Subsequent reaction of the indole systems with primary carboxamides in the presence of AlMe3 gives exclusively the C‐3 substituted imine product.

Mild Reductive Functionalization of Amides into N‐Sulfonylformamidines

“…and Phakhodee et al. (Scheme 1 b and c) . The direct condensation of sulfonamides with N , N ‐dimethylformamide dimethyl acetal (DMF‐DMA) was furthermore reported by Sharma and co‐workers, and N ‐sulfonylformamidines can also be prepared from cyanamides …”

“…[12] Later,p rotocols based on AlMe 3 and Ph 3 P/I 2 for amide activation and subsequenta midine synthesis were also reported by Velavan et al andP hakhodee et al (Scheme 1b and 1c). [13,14] The direct condensation of sulfonamides with N,N-dimethylformamide dimethyl acetal (DMF-DMA) was furthermore reported by Sharma and co-workers, [15] and N-sulfonylformamidines can also be prepared from cyanamides. [16] The development of the chemoselectiver eduction of amides has been very successful and, today,f unctional groups such as ketones, aldehydes,a nd imines can be tolerated.…”

A Modular and Convergent Synthetic Route to Supramolecular Cyclic Dimers Based on Amidinium‐Carboxylate Interactions

“…Recognition units in the hands must be conveniently protected to avoid undesired reactions and facilitate purification processes during consecutive C−C couplings along the route. In order to obtain a highly convergent approach, we chose a common methyl ester precursor for the generation of both recognition units: firstly the corresponding carboxylic acid, via hydrolysis of the ester, and then the amidine, via an amide intermediate (see below) [11] …”

“…In order to generate the final monomers equipped with carboxylic acid On the other hand, the formation of corresponding amidines was successfully achieved following a protocol described in the literature (Scheme 5). [11] This method starts with the activation of the carboxylic acid functions in C(0.0), C(0.1), C(1.0) and C(1.1) as the corresponding acid chlorides, in the presence of (COCl) 2 and a catalytic amount of DMF, followed by their transformation into the corresponding primary amides M(0.0), M(0.1), M(1.0) and M(1.1), by reaction with ammonium hydroxide. [17] Subsequently, a final reaction with an amine, in particular ethylamine, mediated by trimethylaluminium (AlMe 3 ), [11] afforded, after washing with concentrated NaOH solutions to ensure amidine deprotonation, [18] as corroborated by 1 H and 13 C NMR, the N-ethyl substituted amidines A(0.0), A(0.1), A(1.0) and A(1.1) in high yield.…”

“…In order to obtain a highly convergent approach, we chose a common methyl ester precursor for the generation of both recognition units: firstly the corresponding carboxylic acid, via hydrolysis of the ester, and then the amidine, via an amide intermediate (see below). [11] Synthesis of the Molecular Fragments Synthesis of the core. The synthesis of the target final compounds starts with the preparation of the cores.…”