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

Jiang, Yuan‐Ye; Man, Xiaoping; Bi, Siwei

doi:10.1007/s11426-016-0330-3

Cited by 47 publications

(17 citation statements)

References 251 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thereafter, the anion exchange of CP4 with K 2 CO 3 generates KBr and CP7 , from which inner-sphere carbonate-assisted C(sp 3 )–H activation occurs via TS3 . Despite this common type of C–H activation process, the transition state with the presence of KBr, i.e. TS4 , was found to be more favored by 2.2 kcal/mol.…”

Section: Resultsmentioning

confidence: 94%

Mechanism of Palladium-Catalyzed Alkylation of Aryl Halides with Alkyl Halides through C–H Activation: A Computational Study

et al. 2018

Self Cite

View full text Add to dashboard Cite

Pd-catalyzed C(sp3)–H activation/alkylation of 2-tert-butylaryl halides with alkyl halides and CH2Br2 represents an advantageous strategy for the C–H functionalization with halogens as traceless directing groups. Several possible mechanisms were proposed for the reactions, but no further evidence was available to judge their relative feasibilities. Herein, a mechanistic study was performed with the aid of density functional theory (DFT) methods. Calculations indicate that the coupling of aryl bromides with alkyl chlorides is likely to generate alkylated benzocyclobutenes via aryl–Br oxidative addition on Pd(0) catalysts, C(sp3)–H activation, alkyl–Cl oxidative addition, aryl–alkyl reductive elimination, aryl–H activation, and aryl–C(sp3) reductive elimination. The coupling of aryl iodides with CH2Br2 is likely to generate indane derivatives via aryl–I oxidative addition, C(sp3)–H activation, alkyl–Br oxidative addition, aryl–CH2Br reductive elimination, alkyl–Br oxidative addition, C(sp3)–alkyl reductive elimination, and reduction of palladium dibromide complexes by amines. By comparison, the metathesis of alkyl chlorides on Pd(II) intermediates and the pathway involving palladium carbene intermediates are found to be less favored. Meanwhile, the coordination of in situ generated salts KI, KBr, and KHCO3 to palladium complexes, which has been less considered in previous mechanistic studies, is found to lead to more energetically favored pathways in most of the steps. Finally, the oxidative addition of alkyl halides generating Pd(IV) intermediates or the reduction of palladium dibromide complexes by amines, rather than the previously proposed C(sp3)–H activation, is found to be the rate-determining step in the two types of coupling reactions. This result does not go against the reported primary kinetic isotope effect (KIE) based on intramolecular competition reactions because the C(sp3)–H activation is irreversible according to our calculations.

show abstract

Section: Resultsmentioning

confidence: 94%

Mechanism of Palladium-Catalyzed Alkylation of Aryl Halides with Alkyl Halides through C–H Activation: A Computational Study

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our computational studies provided strong support for a facile C–H ruthenation, along with a rate-determining protodemetalation by the solvent acetic acid. Furthermore, our detailed DFT analysis highlighted the role of the various η 6 -arene ligands, and the key importance of mono-cationic ruthenium(II) complexes 55 as the crucial intermediates for a facile base-assisted internal electrophilic substitution 56,57 C–H activation, the results of which are described in the Supplementary Fig. 16.…”

Section: Resultsmentioning

confidence: 95%

Late-stage peptide C–H alkylation for bioorthogonal C–H activation featuring solid phase peptide synthesis

et al. 2019

View full text Add to dashboard Cite

Methods for the late-stage diversification of structurally complex peptides hold enormous potential for advances in drug discovery, agrochemistry and pharmaceutical industries. While C–H arylations emerged for peptide modifications, they are largely limited to highly reactive, expensive and/or toxic reagents, such as silver(I) salts, in superstoichiometric quantities. In sharp contrast, we herein establish the ruthenium(II)-catalyzed C–H alkylation on structurally complex peptides. The additive-free ruthenium(II)carboxylate C–H activation manifold is characterized by ample substrate scope, racemization-free conditions and the chemo-selective tolerance of otherwise reactive functional groups, such as electrophilic ketone, bromo, ester, amide and nitro substituents. Mechanistic studies by experiment and computation feature an acid-enabled C–H ruthenation, along with a notable protodemetalation step. The transformative peptide C–H activation regime sets the stage for peptide ligation in solution and proves viable in a bioorthogonal fashion for C–H alkylations on user-friendly supports by means of solid phase peptide syntheses.

show abstract

“…A DFT study was performed by employing the Gaussian09 program in solution-phase with SMD solvent model (solvent = dimethyl sulfoxide). The M06-2X method, which is recommended by Truhlar et al for main-group thermochemistry and kinetics, was used in conjunction with an ultrafine integration grid and the basis set def2-SVP developed by Ahlrichs and Weigend . Geometry optimization was conducted without structural restraint unless mentioned otherwise.…”

Section: Computational Methodsmentioning

confidence: 99%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 47 publications

References 251 publications

Mechanism of Palladium-Catalyzed Alkylation of Aryl Halides with Alkyl Halides through C–H Activation: A Computational Study

Mechanism of Palladium-Catalyzed Alkylation of Aryl Halides with Alkyl Halides through C–H Activation: A Computational Study

Late-stage peptide C–H alkylation for bioorthogonal C–H activation featuring solid phase peptide synthesis

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

Contact Info

Product

Resources

About