N-heterocyclic carbene-catalyzed direct enantioselective synthesis of dihydroisoxazolo[5,4-<i>b</i>]pyridin-6-ones

Huang, Xiaoxia; Li, Yarui; He, Jieyin; Peng, Shiyong; Wang, Jian; Lang, Ming

doi:10.1039/d2qo01736a

Cited by 7 publications

(7 citation statements)

References 54 publications

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“…On the basis of the experimental results of Wang and Lang’s group and our computations, we proposed a mechanism for the [3 + 3] annulation reaction involving α-bromoenal and 5-aminoisoxazole catalyzed by NHC. Scheme outlines the essential steps of the catalytic cycle.…”

Section: Resultsmentioning

confidence: 91%

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

Zhang,

2024

J. Org. Chem.

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Density functional theory (DFT) calculations were conducted to explore the mechanisms and origins of regio-and stereoselectivities underlying the [3 + 3] annulation reaction between α-bromoenals and 5-aminoisoxazoles with N-heterocyclic carbene (NHC) as the catalyst. The reaction occurs in nine steps:(1) nucleophilic addition of NHC to α-bromoenal, (2) Breslow intermediate formation through 1,2-proton transfer, (3) debromination, (4) α,β-unsaturated acyl azolium intermediate formation via 1,3-proton transfer, (5) addition of α,β-unsaturated acyl azolium intermediate to 5-aminoisoxazole, (6) deprotonation, (7) protonation, (8) ring closure, and (9) elimination of NHC. For the fifth step, 1,2-addition suggested in the experiment was not supported by our results. Instead, we found that Michael addition is energetically the most feasible pathway and the stereocontrolling step that preferentially provides the S-configuration product. DFT-computed results and experimental findings agree well. Analysis of distortion/interaction reveals that lower distortion energy leads to stability of the transition state corresponding to the Sconfiguration product. Global reactivity index analysis indicates that the behavior of the NHC catalyst differs significantly before and after the Breslow intermediate debromination. Before debromination, the nucleophilicity of α-bromoenal is enhanced by addition to NHC. However, after debromination, the α,β-unsaturated acyl azole generates and acts as an electrophilic reagent.

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Section: Resultsmentioning

confidence: 91%

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

Zhang,

2024

J. Org. Chem.

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“…According to the mechanism in Scheme 36, the addition of NHC E to α-bromoenal 1 led to Breslow intermediate I, which was transformed into the α,β-unsaturated acyl azolium intermediate II through tautome- [5,4b]pyridin-6-one derivative by using an NHC catalyst. [39] In the method, (3 + 3)-annulation between 2-bromoenals and 5aminoisoxazoles occurred under mild reaction conditions. A similar mechanistic pathway as previous work was proposed for this transformation.…”

Section: Nhc-catalyzed Synthesis Of N-heterocyclesmentioning

confidence: 99%

“…On the other hand, intermediate IV also can be produced via the 1,4‐addition of 56 to II (path b). In another work by Wang and Lang, they succeeded in synthesizing dihydroisoxazolo [5,4‐ b ]pyridin‐6‐one derivative by using an NHC catalyst [39] . In the method, (3+3)‐annulation between 2‐bromoenals and 5‐aminoisoxazoles occurred under mild reaction conditions.…”

Section: Nhc‐catalyzed Synthesis Of Heterocyclesmentioning

confidence: 99%

NHC‐Catalyzed Enantioselective Transformations Involving α‐Bromoenals

Doraghi,

Ameli,

Ansariashlaghi

et al. 2024

The Chemical Record

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Abstractα‐Haloenals, especially, α‐bromoenals considered as one of the important building blocks in organic synthesis. They can participate in various (3+2)‐, (3+3)‐, (3+4)‐, and (2+4)‐annulation reactions with other organic molecules in the presence of an NHC catalyst to produce enantioenriched carbo‐, and heterocyclic compounds. Herein, we have described NHC‐catalyzed enantioselective transformations of α‐bromoenals in the synthesis of various heterocycles, and carbocycles, as well as acyclic organic compounds.

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“…48 The dispersion interaction, a key weak attractive force, has been elaborated to significantly contribute to the success of hydrogenation of CQN bond. 49 3.1.2. Hydrogenation of CQ Q QO bonds.…”

Section: Hydrogenationmentioning

confidence: 99%

Chiral bisphosphine Ph-BPE ligand: a rising star in asymmetric synthesis

Mei,

Ma,

Chen

et al. 2024

Chem. Soc. Rev.

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N-heterocyclic carbene-catalyzed direct enantioselective synthesis of dihydroisoxazolo[5,4-b]pyridin-6-ones

Abstract: A novel N-heterocyclic carbene (NHC)-catalyzed asymmetric [3+3] cycloaddition between α-bromoenals and 5-aminoisoxazoles has been developed. With this method, various dihydroisoxazolo[5,4-b]pyridin-6-ones were obtained in high yields (up to 99%) with excellent...

Cited by 7 publications

References 54 publications

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

NHC‐Catalyzed Enantioselective Transformations Involving α‐Bromoenals

Chiral bisphosphine Ph-BPE ligand: a rising star in asymmetric synthesis

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