title: A Ligand-Dissociation-Involved Mechanism in Amide Formation of Monofluoroacylboronates with Hydroxylamines.
abstract: Acylborons, as a growing class of boron reagents, were successfully applied to amide ligation and showed potential in chemoselective bioconjugation reactions in recent years. In this manuscript, a density functional theory (DFT) study was performed to investigate the mechanism of the amide formation between monofluoroacylboronates and hydroxylamines. An updated pathway was clarified herein, including water-assisted hemiaminal formation, pyridine ligand dissociation, elimination via a six-membered-ring transition state, and water-assisted tautomerization. The proposed mechanism was further examined by applying it to investigate the activation barriers of other monofluoroacylboronates, and the related calculations well reproduced the experimentally reported relative reactivities. On the basis of these results, we found that the ortho substitution of the pyridine ligand destabilizes the acylboron substrates and the hemiaminal intermediates by steric effects and thus lowers the energy demand of the ligand dissociation and elimination steps. By contrast, the para substitution of the pyridine ligand with an electron-donating group enhances the coordination of the ligand by electronic effects, which is a disadvantage to the ligand dissociation and elimination steps. The ligand bearing a rigid linkage blocks the rotation of the pyridine ligand and makes ligand dissociation difficult.
authors.affiliation: School of Chemistry and Chemical Engineering, Qufu Normal University , Qufu 273165, People's Republic of China.
authors.forename: Yuan-Ye
authors.identifier: 0000-0002-4763-9173
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University , Shaoxing 312000, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Chemistry and Chemical Engineering, Qufu Normal University , Qufu 273165, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Chemistry and Chemical Engineering, Qufu Normal University , Qufu 273165, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Man
authors.affiliation: School of Chemistry and Chemical Engineering, Qufu Normal University , Qufu 273165, People's Republic of China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Bi
authors.affiliation: Collaborative Innovation Center of Chemistry for Energy Materials, CAS Key Laboratory of Urban Pollutant Conversion, Department of Chemistry, University of Science and Technology of China , Hefei 230026, People's Republic of China.
authors.forename: Yao
authors.identifier: 0000-0003-2282-4839
authors.initials: Y
authors.lastname: Fu