Nitrogen–boron coordination versus OH⋯N hydrogen bonding in pyridoxaboroles – aza analogues of benzoxaboroles

Abstract

Pyridoxaboroles - fused heterocyclic systems composed of pyridine and five-membered oxaborole rings - have been obtained for the first time from simple halopyridines. Thus, 6-butyl-2-(3'-bromo-4'-pyridyl)-(N-B)-1,3,6,2-dioxazaborocan obtained from 3-bromopyridine was converted into a lithio derivative by Br/Li exchange using nBuLi/THF at -85 °C. This intermediate was trapped with benzaldehydes to give the corresponding pyridoxaboroles after hydrolysis. The use of chlorodiphenylsilane as an electrophile gave rise to a related pyridosiloxaborole. The fluorinated pyridoxaborole was obtained by deprotonation of α-(2-methoxyphenyl)-2-fluoro-4-iodopyridylmethanol with NaH and consecutive iodine-lithium exchange/boronation followed by hydrolysis. Single-crystal X-ray analysis of pyridino[4,3-c]-1,3-dihydro-1-hydroxy-3-mesityl[2,1]oxaborole revealed the formation of a unique 1D coordination polymer based on N-B dative bonds between monomeric molecules. In contrast, the crystal structure of 2-fluoropyridino[4,3-c]-1,3-dihydro-1-hydroxy-3-(2'-methoxyphenyl)[2,1]oxaborole features an infinite H-bonded chain as the main structural motif. The presented considerations are quantified in terms of various computational methods (single molecule and dimer energy calculations, electron density topology, NBO analyses) providing a comprehensive picture of the structural properties of pyridoxaboroles.

Synthesis and Transformations of Functionalized Benzosiloxaboroles

“…This is mainly due to the discovery of potent antimicrobial activity of functionalized derivatives, [2,3] amply demonstrated by the recent approval of Tavaborole (trade name Kerydin) [4] for the treatment of onychomycosis, a fungal infection of the nail and nail bed. [7] The importance and potential wide applicability of benzoxaboroles has prompted us to develop the synthetic routes to their analogues: pyridoxaboroles [8] and benzosiloxaboroles (Scheme 1, II). [5] Importantly, benzoxaboroles are stronger Lewis acids than the corresponding arylboronic acids, [6] which is beneficial for the solubility in water at neutral pH.…”

Heteroelement Analogues of Benzoxaborole and Related Ring Expanded Systems

“…When heated in THF at 80 • C, it undergoes transformation to complex 51 with the DBU ligand coordinated to the boron atom in 49. The bromine-lithium exchange reaction of ortho-(dimethylsilyl)bromobenzene with t-BuLi, followed by trapping with (isopropoxy)diarylboranes (52-53), resulted in borohydride intermediates (56-57), which form neutral ortho-(alkoxysilyl)(diarylboryl)benzenes The bromine-lithium exchange reaction of ortho-(dimethylsilyl)bromobenzene with t-BuLi, followed by trapping with (isopropoxy)diarylboranes (52)(53), resulted in borohydride intermediates (56)(57), which form neutral ortho-(alkoxysilyl)(diarylboryl)benzenes (58-59) after the addition of chlorotrimethylsilane. The formation of 56-57 can be explained in terms of intramolecular hydride-isopropoxide exchange between silicon and boron atoms in initially formed unstable alkoxyborate complexes (54-55) (Scheme 18) [39].…”

“…The formation of 56-57 can be explained in terms of intramolecular hydride-isopropoxide exchange between silicon and boron atoms in initially formed unstable alkoxyborate complexes (54-55) (Scheme 18) [39]. The bromine-lithium exchange reaction of ortho-(dimethylsilyl)bromobenzene with t-BuLi, followed by trapping with (isopropoxy)diarylboranes (52)(53), resulted in borohydride intermediates (56)(57), which form neutral ortho-(alkoxysilyl)(diarylboryl)benzenes (58)(59) after the addition of chlorotrimethylsilane. The formation of 56-57 can be explained in terms of intramolecular hydride-isopropoxide exchange between silicon and boron atoms in initially formed unstable alkoxyborate complexes (54-55) (Scheme 18) [39].…”

“…Compound 161 was subjected to N -methylation, resulting in the cationic heterocycle ( 162 ). Pyridosiloxaborole ( 163 ) was obtained when Ph 2 Si(H)Cl was used as an electrophilic reagent ( Scheme 39 ) [ 52 ].…”

Differential Sensing of Saccharides Based on an Array of Fluorinated Benzosiloxaborole Receptors

“…This results not only in improved solubility in water at neutral pH but also may be beneficial for ability to bind various cis-1,2-diols, including biologically important saccharides, nucleosides, and catechol derivatives [ 7 , 8 ]. The importance and potential wide applicability of benzoxaboroles has prompted us to develop their analogues, namely pyridoxaboroles [ 9 ] and benzosiloxaboroles [ 10 ]. Thus, in the former case the benzene ring of benzoxaborole was replaced with a pyridine one, whereas in the latter the five-membered ring comprising silicon atom was constructed.…”