Boric Acid Catalyzed Direct Amidation between Amino-Azaarenes and Carboxylic Acids

Abstract

A novel and facile boric acid catalyzed direct amidation between amino-azaarene compounds and carboxylic acids has been developed. The amidation proceeded cleanly and provided good to excellent yields of the desired amides. Boric acid is a green and inexpensive catalyst. We have also found that N,N,N′,N′-tetramethylpropane-1,3-diamine acted as an additive accelerating this boric acid catalyzed amidation. A mixed acid anhydride is postulated to be the active intermediate responsible for this successful amidation. This direct amidation is an atom-and step-economical reaction.

On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids

“…There are very few reports on high-yielding catalytic amidation reactions of aromatic carboxylic acids in the ideal 1:1 acid/amine stoichiometry in the literature, − and perhaps unsurprisingly, catalytic quantities of bromosilanol 6h failed to provide any quantities of amides 3f–3h , which are among the most difficult combinations of acid and amine (Figure ). Pleasingly, some activity was found for the formation of aromatic amide 3e albeit in low conversion after 24 h. Aliphatic amide 3a was formed in quantitative yield in a reaction time of 6 h, albeit where the background reaction is itself complete in 24 h. This result demonstrates the need to run background reactions when reporting direct amidation reactions.…”

“…However, while there are several reports of successful silicon-based reagents and silica gels for direct amidation, there are no examples of silicon-centered molecular catalysts for direct amidations . Furthermore, while various proposals for the mechanistic operation of catalytic amidations have been moot, − only limited direct experimental evidence for presumed activated intermediates has been garnered . Herein, we report on the discovery, synthesis, and use of various electronically differentiated triarylsilanols as the first silicon-centered molecular catalysts for direct amidation.…”

“…The catalytic amidation of carboxylic acids thereby avoiding stoichiometric quantities of activating agent is the focus of much current research . Significant progress has been made with the development of boron-based catalysts, − oxophilic metal catalysts, and other catalytic systems . However, while there are several reports of successful silicon-based reagents and silica gels for direct amidation, there are no examples of silicon-centered molecular catalysts for direct amidations .…”

Toward a Practical Catalyst for Direct Amidation of Carboxylic Acids with Pyridine‐Borane Complexes

“…From the perspective of cost and environmental consideration, the feedstock carboxylic acids are attractive substrates for the direct synthesis of amides, with water being the only byproduct [2] . In this context, a range of catalytic methods have been successfully established for activating carboxylic acids, such as transition‐metal catalysis, [2a,b] visible light photoredox catalysis, [2c,d] electrochemical synthesis [2e] and organoboron reagent‐based catalysis [2f–n] . At the beginning, Yamamoto, Ishihara and Hall have documented boronic acids as efficient catalysts for the direct amidation of carboxylic acids, [2f–k] subsequently several other types of borane‐based catalysts such as boric acid, [2l] borate esters [2m] and ammonia‐borane [2n] also have been developed (Scheme 1b).…”

Emergent Organoboron Acid Catalysts

“…Since these reports, a number of groups have developed the use of boric acid, − borinic acids, − or boronic acids − as catalysts for esterification and amidation reactions, including applications in peptide synthesis, ,, the total synthesis of natural products, and the synthesis of active pharmaceutical ingredients . A few noteworthy examples are highlighted here, focusing on unique catalyst systems and mechanistic analyses.…”