Neighboring Protonation Unveils Lewis Acidity in the B₃NO₂ Heterocycle

Abstract

Boron serves a distinctive role in a broad range of chemistry disciplines. The utility of the element lies in its Lewis acidity, and thus, it is crucial to understand the properties of the boron atom in chemically different contexts. Herein, a combination of experiments and computations reveals the nuanced nature of boron in direct amidation reactions catalyzed by recently disclosed 1,3-dioxa-5-aza-2,4,6-triborinanes (DATBs). The most active DATB catalyst has been shown to bear an azaborine ring in its structure, thus having four boron atoms in a single molecule. Three chemically distinct boron atoms in the catalyst framework have been shown to serve different roles in the catalytic cycle, depending on their innate Lewis acidity. More specifically, the most Lewis acidic boron interacts with the amine, whereas the two boron atoms in the B–N–B substructure acquire Lewis acidity only upon protonation of the center nitrogen atom. Furthermore, although the least acidic boron atom in the azaborine ring did not act as a Lewis acid, it still plays an important role in the catalytic cycle by forming a hydrogen bond between carboxylic acid and the B–OH moiety. The mechanistic insights obtained from this study not only extend the knowledge on catalytic direct amidation but also provide a guiding principle for the further exploration of multi-boron compounds.

Recent developments in catalytic amide bond formation

“…[60] The same group later studied the mechanism of the reaction in greater detail, yielding insight into the unique Lewis acidity of each boron in the complex and their respective roles in different steps in the catalytic cycle. [61] As the synthesis of the first generation catalysts was tedious, a more facile approach to equally potent DATBs analogs based on pyrimidines (Pym-DATBs) was reported in 2019. [62] DATBs were also applied to the coupling of standard Fmoc protected amino acids amino acids to yield simple polypeptides [63] that included sidechains featuring…”

All Non‐Carbon B3NO2 Exotic Heterocycles: Synthesis, Dynamics, and Catalysis

“…The DATB containing the m ‐terphenyl scaffold demonstrated promise in the catalytic dehydrative amidation of carboxylic acids and amines, and therefore, we next turned our attention to evaluating the catalytic competency of the newly developed Pym‐DATBs in detail. Amide bond formation is undoubtedly one of the most important and frequently employed reactions in industry, producing a wide range of indispensable commodities and specialty chemicals, from functional polymers to pharmaceuticals.…”

The Dynamic Covalent Chemistry of Amidoboronates: Tuning the rac5/rac6 Ratio via the B−N and B−O Dynamic Covalent Bonds

“…In materials science this has been exploited to tune the optoelectronic [1d,f,i,k,4] and self‐healing [5] properties of materials. Furthermore, amidation reactions have been catalysed by BN‐containing heterocycles, [1e,6] and FLPs [2,7] enable small molecule activation (e. g. H 2 , CO 2 ) and catalysis as an alternative to transition metal catalysts.…”