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

Abstract

The B3NO2 six‐membered heterocycle (1,3‐dioxa‐5‐aza‐2,4,6‐triborinane=DATB), comprising three different non‐carbon period 2 elements, has been recently demonstrated to be a powerful catalyst for dehydrative condensation of carboxylic acids and amines. The tedious synthesis of DATB, however, has significantly diminished its utility as a catalyst, and thus the inherent chemical properties of the ring system have remained virtually unexplored. Here, a general and facile synthetic strategy that harnesses a pyrimidine‐containing scaffold for the reliable installation of boron atoms is disclosed, giving rise to a series of Pym‐DATBs from inexpensive materials in a modular fashion. The identification of a soluble Pym‐DATB derivative allowed for the investigation of the dynamic nature of the B3NO2 ring system, revealing differential ring‐closing and ‐opening behaviors depending on the medium. Readily accessible Pym‐DATBs proved their utility as efficient catalysts for dehydrative amidation with broad substrate scope and functional‐group tolerance, offering a general and practical catalytic alternative to reagent‐driven amidation.

Recent developments in catalytic amide bond formation

“…[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…”

“…Yamamoto. [120] Furthermore, if a stereoselective variant of this sys- Kumagi [62,63] Yamamoto (methyl ester amidation [121] )…”

Formamide catalyzed activation of carboxylic acids – versatile and cost-efficient amidation and esterification

“…Intriguing protocols for amidation without the necessity of reagents have been recently established based on boron,4–7 hafnium and zirconium8 Lewis acid catalysts, for example 1e,g–k,m. The latest generation of catalysts such as the remarkable dioxoazatriborinane of Shibasaki and Kumagai, which is prepared in five steps, allows even for the synthesis of amides derived from challenging aromatic and sterically encumbered aliphatic carboxylic acids 6,7…”

Direct Boronic Acid Promoted Amidation of Carboxylic Acids with Poorly Nucleophilic Amines

“…[12] A number of newer boronic acids and borate catalysts were described that efficiently promote the direct amide bond formation of aliphatic amines at temperatures ranging from ambient to moderate, and over 100 °C. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] For example, 5-methoxy-2-iodophenyl boronic acid (MIBA), [15][16][17] a catalyst developed in this laboratory, affords amide products of aliphatic amines and carboxylic acids in high yields within reaction times of 2-48 hours at ambient temperature. In a significant advance, Ishihara and co-workers reported that 3,5bis(trifluoromethyl)phenylboronic acid, when used in cooperation with 4-(N,N-dimethylamino)pyridine N-oxide (DMAPO), can catalyze the direct amidation reaction of hindered aliphatic and less reactive aromatic carboxylic acids under azeotropic reflux conditions.…”