Isolation and characterization of an annelated N-heterocyclic carbene stabilized Breslow enolate

Li, Xin; Ren, Yan-Yan; Chen, Can; Sun, Li-Ying; Han, Ying-Feng

doi:10.1039/d3qo01644g

Cited by 2 publications

(1 citation statement)

References 57 publications

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“…On the other hand, stemming from the groundbreaking contributions of Studer [ 37 , 38 ], Ohmiya [ 39 , 40 ], and Chi [ 41 ] et al, NHC-attached persistent Breslow intermediate radicals (BIR) [ 42 , 43 , 44 ] have emerged as valuable acyl radical equivalents, enabling radical-radical cross-coupling and thereby paving the way for a new paradigm in radical acylation chemistry [ 45 , 46 , 47 , 48 ]. In radical NHC catalysis, persistent BIR and transient radical species can be concurrently generated at a comparable rate through a single electron transfer process.…”

Section: Introductionmentioning

confidence: 99%

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

Xia,

Guo,

et al. 2024

Molecules

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Monofluoromethyl (CH2F) motifs exhibit unique bioactivities and are considered privileged units in drug discovery. The radical monofluoromethylative difunctionalization of alkenes stands out as an appealing approach to access CH2F-containing compounds. However, this strategy remains largely underdeveloped, particularly under metal-free conditions. In this study, we report on visible light-mediated three-component monofluoromethylation/acylation of styrene derivatives employing NHC and organic photocatalyst dual catalysis. A diverse array of α-aryl-β-monofluoromethyl ketones was successfully synthesized with excellent functional group tolerance and selectivity. The mild and metal-free CH2F radical generation strategy from NaSO2CFH2 holds potential for further applications in fluoroalkyl radical chemistry.

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Section: Introductionmentioning

confidence: 99%

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

Xia,

Guo,

et al. 2024

Molecules

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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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Isolation and characterization of an annelated N-heterocyclic carbene stabilized Breslow enolate

Abstract: The highly reactive intermediate (Breslow enolate) of NHC-catalyzed radical reactions has been successfully synthesized and structurally characterized by X-ray diffraction for the first time.

Cited by 2 publications

References 57 publications

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

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

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