Prediction on the origin of selectivities of NHC-catalyzed asymmetric dearomatization (CADA) reactions

Wang, Yan; Wu, Qiuyu; Lai, Tianhua; Zheng, Kaijun; Qu, Lingbo; Wei, Donghui

doi:10.1039/c8cy02238k

Cited by 54 publications

(8 citation statements)

References 88 publications

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“…The one-pot, albeit stepwise four components sequence, was also successfully developed by the in-situ formed isoquinolinium precursor 109 followed by the addition of the other components. Based on the recent DFT computational investigations by Qu, Wei and colleagues, this domino reaction is believed to proceed through a stepwise fashion starting with the regio-and enantioselective Mannich reaction at C1, followed by the diastereoselective cyclization [74]. Importantly, the use of ethanol as an additive was crucial to secure the ethanolysis event of the acyltriazolium intermediate C22 in order to regenerate the NHC catalyst.…”

Section: Isoquinolinium Saltsmentioning

confidence: 99%

Organocatalysis: A Tool of Choice for the Enantioselective Nucleophilic Dearomatization of Electron-Deficient Six-Membered Ring Azaarenium Salts

et al. 2021

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Nucleophilic dearomatization of azaarenium salts is a powerful strategy to access 3D scaffolds of interest from easily accessible planar aromatic azaarene compounds. Moreover, this approach yields complex dihydroazaarenes by allowing the functionalization of the scaffold simultaneously to the dearomatization step. On the other side, organocatalysis is nowadays recognized as one of the pillars of the asymmetric catalysis field of research and is well-known to afford a high level of enantioselectivity for a myriad of transformations thanks to well-organized transition states resulting from low-energy interactions (electrostatic and/or H-bonding interactions…). Consequently, in the last fifteen years, organocatalysis has met great success in nucleophilic dearomatization of azaarenium salts. This review summarizes the work achieved up to date in the field of organocatalyzed nucleophilic dearomatization of azaarenium salts (mainly pyridinium, quinolinium, quinolinium and acridinium salts). A classification by organocatalytic mode of activation will be disclosed by shedding light on their related advantages and drawbacks. The versatility of the dearomatization approach will also be demonstrated by discussing several chemical transformations of the resulting dihydroazaarenes towards the synthesis of structurally complex compounds.

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Section: Isoquinolinium Saltsmentioning

confidence: 99%

Organocatalysis: A Tool of Choice for the Enantioselective Nucleophilic Dearomatization of Electron-Deficient Six-Membered Ring Azaarenium Salts

et al. 2021

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“…The intrinsic reaction coordinate (IRC) , calculations were performed at the same level of theory to ensure the transition states could connect the reactants and expected product. Single point energy of all the optimized structures were further calculated at the M06-2X-D3/6-31+G(d,p) level with SMD model to obtain their accurate energies, which has been proved to be a powerful method for investigating the mechanism of organic chemistry. − The optimized structures and frontier molecular orbital theory (FMOT) were displayed with CYLview (version 1.0b) and GaussView (Version 5) softwares, respectively.…”

Section: Computational Detailsmentioning

confidence: 99%

Mechanistic Study of 1,4-Benzodiazepine-2,5-diones from Diphenylamine and Diethyl 2-Phenylmalonate by Density Functional Theory

Zhou

2019

J. Phys. Chem. A

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The mechanisms for the reaction between diphenylamine and diethyl 2phenylmalonate were investigated using M06-2X-D3/6-31+G(d,p) method and level, and the SMD model was applied to simulate the solvent effect. The computational results suggested that diphenylamine and diethyl 2-phenylmalonate can convert into 4hydroxy-1,3-diphenylquinolin-2(1H)-one via a series of reactions (addition reaction, dealcoholization reaction, enolization reaction, dealcoholization reaction, ring-closure reaction, and H-shift reaction). And H 2 O, as the catalyst, can play an important role to promote these reactions. In the following reaction, there are two paths to yield the second product 3-chloro-1,3-diphenylquinoline-2,4(1H,3H)-dione and the computational results indicated that the first path (blue line) with the rate-determining step of 24.9 kcal/mol is favorable. With the participation of methanamine, a SN2 reaction happened and the third product 3-(methylamino)-1,3-diphenylquinoline-2,4(1H,3H)-dione had been yielded in the effect of methanamine or Cl anion. The analysis of Gibbs free energy surfaces shows that methanamine is better than Cl anion to extract the proton via an exothermic reaction. Finally, the third product 3-(methylamino)-1,3-diphenylquinoline-2,4(1H,3H)-dione would go through a ring-enlargement reaction, promoted by base (TMG or Triton B), to yield the final product. The computational results demonstrated that this reaction can release much energy with Triton B than that with TMG. And the energy of the highest point is 10.1 kcal/mol (16.8 kcal/mol), which can readily occur at the room temperature. The results could provide valuable insights into these types of interactions and related ones.

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“…Nitrogen-containing heterocycles are important intermediates in many organic synthesis reactions and are also substructures in medicines and natural products, especially in bioactive molecules. , In recent years, it has been one of the hottest research topics in chemical synthesis to find a more effective method that uses N -heterocyclic carbene (NHC) as a catalyst to form these products. , NHCs as efficient and convenient tools also have a wide range of applications and great potential for the synthesis of various asymmetric products except metal and enzyme catalysts. − NHCs have considerable versatility and selectivity in promoting the conversion and organic synthesis of many organic compounds, such as the Breslow intermediates, , α–β unsaturated acyl heterocycles, acyl heterocycles, alkenes, and so on. − It is because of their unique property of polarity reversal that they can react with aldehydes or ketones to produce homoenolates and acyl compounds in a variety of organic transformations, which leads to the diversification of reaction pathways. More importantly, NHCs have been successfully applied in the formation of a C–C or C–heteroatom bond in various reactions, such as the homoenoic acid reaction, Stetter reaction, Claisen rearrangement, Michael addition, C–H bond activation, C–C bond activation, cycloaddition, and other types of cyclization reactions …”

Section: Introductionmentioning

confidence: 99%

Theoretical Insights into Enantioselective [3 + 2] Cycloaddition between Cinnamaldehyde and Cyclic N-Sulfonyl Trifluoromethylated Ketimine Catalyzed by N-Heterocyclic Carbene

2022

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The density functional theory (DFT) method was used to investigate the mechanism and the origin of stereoselectivity of N-heterocyclic carbene (NHC)-catalyzed [3 + 2] cycloaddition between enals and cyclic imine N-sulfonyl trifluoromethyl ketimines at the M06-2X/SMD/6-311+G(d,p)//M06-2X/SMD/6-31G (d,p) level. The results show that the favorable reaction path consists of five steps: nucleophilic attack, proton transfer, the formation of the C–C bond, the tautomerism of the enol intermediate, the formation of the five-membered ring, and the regeneration of the catalyst. For the process of proton transfer, the base-assisted reaction can reduce the activation free energy and make the reaction easier to occur compared with the direct proton transfer process. The formation of the C–C bond is the crucial step of stereoselectivity, in which two chiral centers and four configurations of intermediates (RR/RS/SR/SS) were generated. The free energy barriers obtained and the noncovalent interaction analysis confirm that the dominant configuration is SS, becoming the final trans-type product observed in experiment. Furthermore, through the analyses of the conceptual DFT and natural atomic charges, it is revealed that NHC acts as a double catalyst, which can not only increase the nucleophilicity of reactants by Lewis base but also activate the C–H bond and promote the proton transfer process. The understanding of the mechanism obtained in this study should be helpful to the other organic catalytic reactions with high stereoselectivity.

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Prediction on the origin of selectivities of NHC-catalyzed asymmetric dearomatization (CADA) reactions

Abstract: The mechanism and origin of selectivities of NHC-catalyzed dearomatization reaction have been theoretically studied.

Cited by 54 publications

References 88 publications

Organocatalysis: A Tool of Choice for the Enantioselective Nucleophilic Dearomatization of Electron-Deficient Six-Membered Ring Azaarenium Salts

Organocatalysis: A Tool of Choice for the Enantioselective Nucleophilic Dearomatization of Electron-Deficient Six-Membered Ring Azaarenium Salts

Mechanistic Study of 1,4-Benzodiazepine-2,5-diones from Diphenylamine and Diethyl 2-Phenylmalonate by Density Functional Theory

Theoretical Insights into Enantioselective [3 + 2] Cycloaddition between Cinnamaldehyde and Cyclic N-Sulfonyl Trifluoromethylated Ketimine Catalyzed by N-Heterocyclic Carbene

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