A DFT study on the reaction mechanisms of phosphonation of heteroaryl N-oxides with H-phosphonates

Zhang, Wei; Zhao, Xiao‐Yang; Qiao, Yan; Guo, Xiaokang; Wang, Yanyan; Wei, Donghui; Tang, Mingsheng; Niu, Jun‐Long

doi:10.1016/j.comptc.2015.08.012

Cited by 10 publications

(7 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the past decades, density functional theory (DFT) has been extensively used as a powerful method to explore the detailed reaction mechanisms, and predict the regioselectivity as well as chemoselectivities in organocatalytic and biological reactions . It is worth mentioning that the DABCO‐catalyzed [2+4] cycloaddition of ethyl allenoate with arylidenoxindole has been theoretically investigated, but the observed regioselectivity is remarkably different from the reaction in this paper.…”

Section: Introductionmentioning

confidence: 93%

Mechanisms and regioselectivities of DABCO/DMAP‐catalyzed [2+4] annulation reactions of allenoate with α,β‐unsaturated cyclic ketimine: A DFT study

Yang

Zhang

Zhao

et al. 2018

J of Physical Organic Chem

Self Cite

View full text Add to dashboard Cite

In the present study, the reaction mechanisms as well as regioselectivities of 1,4-diazabicyclo-[2.2.2] octane (DABCO) and 4-dimethylaminopyridine (DMAP)-catalyzed [2+4] annulation reactions of allenoate with α,βunsaturated cyclic ketimine leading to hydropyridine derivatives have been theoretically investigated using density functional theory (DFT). In general, the amine catalyst can initiate the reaction by nucleophilic attack to allenoate leading to zwitterionic intermediate, which can then react with cyclic ketimine following different reaction mechanisms. For DABCO-catalyzed annulation, the α-attack is more energetically favorable, and the subsequent two consecutive proton transfers followed by intramolecular cyclization along with catalyst regeneration can lead to the α,β-[2+4] cycloadduct. While for DMAP-catalyzed annulation, γ-attack is preferred, and the subsequent intramolecular cyclization followed by catalyst regeneration results into the β,γ-[2+4] cycloadduct. The calculated results are consistent with the experimental observations. Further noncovalent interaction (NCI) analyses reveal that the steric repulsion, hydrogen bond interactions, and intramolecular C─H···π interactions as well as π-π interactions would be responsible for the observed regioselectivities.

show abstract

Section: Introductionmentioning

confidence: 93%

Mechanisms and regioselectivities of DABCO/DMAP‐catalyzed [2+4] annulation reactions of allenoate with α,β‐unsaturated cyclic ketimine: A DFT study

Yang

Zhang

Zhao

et al. 2018

J of Physical Organic Chem

Self Cite

View full text Add to dashboard Cite

show abstract

“…In 2014, Wu's group reported the phosphonation of N ‐oxides at elevated temperatures by direct reaction with H ‐phosphonates 309 , which play a dual role of the activating agent and the nucleophilic source (Scheme 93A) [122] . The reaction mechanism was rationalized by DFT studies calculated at the B3LYP/6‐31G (d, p) level of theory (Scheme 93B) [123] . The H ‐phosphonates exist as mixtures of two tautomers 309 and 309′ , both of which can react to form 312 via intermediates 311 and 311′ , respectively.…”

Section: Simple C2‐h‐functionalizationmentioning

confidence: 98%

“…[122] The reaction mechanism was rationalized by DFT studies calculated at the B3LYP/6-31G (d, p) level of theory (Scheme 93B). [123] The Hphosphonates exist as mixtures of two tautomers 309 and 309', both of which can react to form 312 via intermediates 311 and 311', respectively. The second stage is the dehydration process, for which three possible reaction pathways are proposed: 309-assisted dehydration, 309'-assisted dehydration, and direct dehydration.…”

Section: Miscellaneousmentioning

confidence: 99%

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

et al. 2020

View full text Add to dashboard Cite

While remarkable progress has recently been made for the direct C−H‐functionalization of azines, its application is still limited by a lack of accessible functional groups (primarily carbon‐based) and poor regioselectivity. In contrast, C2‐functionalized pyridines and quinolines can be easily synthesized by treating readily available N‐oxides with various reagents under appropriate activation conditions. This review seeks to comprehensively document the available synthetic methods for introducing functional groups at the C2 position of pyridines and quinolines. In this work, we highlight recent developments in the C2‐functionalization of pyridine and quinoline N‐oxides and address both the mechanisms and regioselectivity of the reactions. We also describe the pathways and reactive species involved in these processes and highlight a number of medically relevant nitrogen heteroaromatics.

show abstract

“…All of the theoretical calculations were carried out in the Gaussian 09 suite of programs. 46 All of the stationary points were optimized by DFT method, which has been proved to be a powerful tool for clarifying the detailed reaction mechanisms in enzymes, 47−51 transition metals, 30,52−58 organocatalysts 27−33,36,53,59−68 catalyzed reactions, and other theoretical studies. 69−76 All of the species were optimized with M06-2X 77−79 density functional and 6-31G(d, p) basis set in chloroform solvent using the integral equation formalism polarizable continuum model (IEF-PCM).…”

Section: Computational Detailsmentioning

confidence: 99%

Theoretical Study on DBU-Catalyzed Insertion of Isatins into Aryl Difluoronitromethyl Ketones: A Case for Predicting Chemoselectivity Using Electrophilic Parr Function

Wei

2017

ACS Omega

Self Cite

View full text Add to dashboard Cite

The possible mechanisms of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed chemoselective insertion of N -methyl isatin into aryl difluoronitromethyl ketone to synthesize 3,3-disubstituted and 2,2-disubstituted oxindoles have been studied in this work. As revealed by calculated results, the reaction occurs via two competing paths, including α and β carbonyl paths, and each path contains five steps, that is, nucleophilic addition of DBU to ketone, C–C bond cleavage affording difluoromethylnitrate anion and phenylcarbonyl–DBU cation, nucleophilic addition of difluoromethylnitrate anion to carbonyl carbon of N -methyl isatin, acyl transfer process, and dissociation of DBU and product. The computational results suggest that nucleophilic additions on different carbonyl carbons of N -methyl isatin via α and β carbonyl paths would lead to different products in the third step, and β carbonyl path associated with the main product 3,3-disubstituted oxindole is more energetically favorable, which is consistent with the experimental observations. Noteworthy, electrophilic Parr function can be successfully applied for exactly predicting the activity of reaction site and reasonably explaining the chemoselectivity. In addition, the distortion/interaction and noncovalent interaction analyses show that much more hydrogen bond interactions should be responsible for the lower energy of the transition state associated with β carbonyl path. The obtained insights would be valuable for the rational design of efficient organocatalysts for this kind of reactions with high selectivities.

show abstract

A DFT study on the reaction mechanisms of phosphonation of heteroaryl N-oxides with H-phosphonates

Cited by 10 publications

References 34 publications

Mechanisms and regioselectivities of DABCO/DMAP‐catalyzed [2+4] annulation reactions of allenoate with α,β‐unsaturated cyclic ketimine: A DFT study

Mechanisms and regioselectivities of DABCO/DMAP‐catalyzed [2+4] annulation reactions of allenoate with α,β‐unsaturated cyclic ketimine: A DFT study

Recent Advances in the Synthesis of C2‐Functionalized Pyridines and Quinolines Using N‐Oxide Chemistry

Theoretical Study on DBU-Catalyzed Insertion of Isatins into Aryl Difluoronitromethyl Ketones: A Case for Predicting Chemoselectivity Using Electrophilic Parr Function

Contact Info

Product

Resources

About