Yuan-Ye Jiang

Advances in theoretical study on transition-metal-catalyzed C−H activation

Transition-metal-catalyzed C–H activation represents one of most attractive research fields in modern organic chemistry while theoretical studies have become a popular and effective tool for elucidating mechanism nowadays. The recent achievements in the cross field of the two orientations are reviewed in this article. The first part introduced the advances in theoretical study on transition-metal-catalyzed C–H activation. The elegant work reported mainly in and after 2013, classified according to the mechanisms of C–H activation, were covered. The second part provided an analysis on the distribution of quantum-chemical methods, solvation models and basis sets in the collected theoretical studies.

A Ligand-Dissociation-Involved Mechanism in Amide Formation of Monofluoroacylboronates with Hydroxylamines.

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.

Mechanism and Rate-Determining Factors of Amide Bond Formation through Acyl Transfer of Mixed Carboxylic–Carbamic Anhydrides: A Computational Study

Acyl transfer of in situ-generated mixed anhydrides is an important method for amide bond formation from short linkages with the easily removed byproduct CO2. To improve our understanding of the inherently difficult acyl transfer hindered by the large ring strain, a density functional theory study was performed. The calculations indicate that the amidation of activated α-aminoesters and N-protected amino acids is more likely to proceed via the self-catalytic nucleophilic substitution of the two substrates and the subsequent 1,3-acyl transfer. By comparison, the mechanism involving 1,5-acyl transfer is less kinetically favored because of the slow homocoupling of activated α-aminoesters. Furthermore, we found that the detailed mechanism of 1,3-acyl transfer on the mixed carboxylic-carbamic anhydrides depends on the catalysts. Strong acidic catalysts and bifunctional catalysts both lead to stepwise pathways, but their elementary steps are different. Basic catalysts cause a concerted C-N bond formation/decarboxylation pathway. The calculations successfully explain the reported performances of different Brønsted-type catalysts and substrates, which validates the proposed mechanism and reveals the dependence of the reaction rates on the acid-base property of catalysts and the acidity of substrates.

Boron Ester-Catalyzed Amidation of Carboxylic Acids with Amines: Mechanistic Rationale by Computational Study

A novel boron ester-catalyzed amidation reaction of carboxylic acids and amines with unprecedented functional group tolerance was recently reported. To gain deeper insights into this reaction, a computational study with density functional theory methods was performed in this manuscript. Calculations indicate that the amidation starts with the condensation of carboxylic acids with the boron ester catalyst. The resulting monoacyloxylated boron species further undergoes the carboxylic acid-assisted nucleophilic addition with amines to generate the amide product and a monohydroxyboron species. The condensation of the carboxylic acid with the monohydroxyboron species with the assistance of an amine regenerates monoacyloxylated boron species to finish the catalytic cycle. The rate-determining step is catalyst regeneration and the amine-coordinated monohydroxyboron species is the resting state in the catalytic cycle. The present results are consistent with the previous NMR study and the observed reaction orders of catalyst and substrates; it is expected to benefit further reaction optimization.