Alkenylazaarenes as dipolarophiles in 1,3-dipolar cycloaddition of nitrones: regioselectivity-switchable and highly diastereoselective synthesis of multisubstituted isoxazolidines

Tong, Mengchao; Zhang, Yong; Qin, Cong; Fu, Yiwei; Liu, Yonghai; Li, Hao; Wang, Wei

doi:10.1039/c8qo00826d

Cited by 13 publications

(2 citation statements)

References 37 publications

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“…Alkenylazaarenes were utilized as dipolarophiles for the preparation of 4-substituted and 5-substituted isoxazolidines with nitrones giving high regioselectivity under a range of reaction conditions. Reaction in water under microwave in a sealed vessel gave in high to excellent yields only 5-substituted isoxazolidines, while the 4-substituted analogs were obtained as the major products when a Lewis acid, TMSOTf, was used as the catalyst in DCM at room temperature (Scheme 15) (Tong et al, 2018).…”

Section: 3-dipolar Cycloaddition In Watermentioning

confidence: 99%

Green Protocols in Heterocycle Syntheses via 1,3-Dipolar Cycloadditions

et al. 2019

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The aim of this review is to provide an overview of green protocols for the organic synthesis of heterocycles via 1,3-dipolar cycloaddition. Particular attention has been devoted to the use of green solvents; reactions performed in ionic liquids, fluorinated solvents and water have been included. Also explored are several protocols that make use of catalyst-free reaction conditions, the use of microwave irradiation and activation by light exposure. Improvements over commonly used organic solvents will be underlined in order to highlight environmental protection aspects and enhancements in regio- and stereo-selectivity.

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Section: 3-dipolar Cycloaddition In Watermentioning

confidence: 99%

Green Protocols in Heterocycle Syntheses via 1,3-Dipolar Cycloadditions

et al. 2019

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“…However, the report by Teterina et al [9] reveals that the reaction between N-arylitaconamides and nitrones proceed regioselectively to give 5-spiroisoxazolidines in high yield. In contrast, Tong et al [10] reported the reaction of alkenylazaarenes with nitrones to yield 4-substituted isoxazolidines with high regio-and diastereoselectives in the presence of Lewis acid as a catalyst. Though this class of reactions has attracted a lot of attention lately, the factors that control the various selectivities are not conclusively known.…”

Section: Introductionmentioning

confidence: 98%

Theoretical investigation of the regio-, enantio-, and stereo-selectivities of the (3 + 2) cycloaddition reactions of N-vinylindoles with nitrones and nitrile oxides

et al. 2021

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The 1,3-dipolar cycloadditions of nitrones and nitrile oxides to N-vinylindole afford isoxazolidines and 5-indolyl-substituted isoxazolines which are structural components of a wide range of natural and pharmaceutically active compounds. In these reactions, there are several regio-, enantio-, and stereo-chemical possibilities, leading to several potential pathways, and these pathways are studied with density functional theory calculations at the M06/6-311G(d,p) level of theory. The results show that the electron-withdrawing substituents on the dipolarophile accelerate the (3 + 2) cycloaddition reactions of nitrones with N-vinylindole by lowering the activation barriers of the reaction. The (3 + 2) cycloaddition of electron-withdrawing and electron-donating substituted nitrones with N-vinylindole proceeds with the preferential formation of cis-stereoisomers, and this is due to the Z-configuration of the nitrone and the trans-periplanar orientation of the substituents and the indolyl group on the transition state. The reactions of nitrile oxides with N-vinylindole proceed regioselectively at the exocyclic double bond in the indole to form 5-indolyl-substituted-isoxazolines. It has been established that the (3 + 2) cycloaddition of electron-donating and electron-withdrawing substituted nitrones and nitrile oxides to N-vinylindole is not enantioselective. The global electrophilicity indices (ω) and maximum electronic charge transfer (ΔN max ) computed for various nitrones and nitrile oxides considered in this work are consistent with energetic trends and experimental outcomes. The analysis of the electrophilic (P k + ) and nucleophilic (P k −) Parr functions at the reactive centers shows that the cycloaddition will happen in such a way as to unite the atoms with the highest molecular orbital coefficients because this would lead to the greatest stabilization, and this is in good agreement with the energetic trends and the experimental outcome.

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