General 5-Halomethyl Isoxazoline Synthesis Enabled by Copper-Catalyzed Oxyhalogenation of Alkenes

Li, Xiaoqing; Ding, Yu; Qian, Lijie; Gao, Yang; Wang, Xinqiang; Yan, Xinhuan; Xu, Xiangsheng

doi:10.1021/acs.joc.9b02031

Cited by 22 publications

(11 citation statements)

References 29 publications

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“…In 2019, Xu's group developed a general and efficient protocol for the rapid synthesis of 5‐halomethyl isoxazolines using commercially available halide sources, such as diethyl bromomalonate, N ‐chlorosuccinimide (NCS), and N ‐iodosuccinimide (NIS) (Scheme 16). [22] This method exhibited the advantages of excellent yield, good substrate expansion, and functional group compatibility.…”

Section: Radical Strategies For Cyclization Of βγ‐Unsaturated Hydrazones and Oximesmentioning

confidence: 99%

Radical Cascade Reactions of β,γ‐Unsaturated Hydrazones/Oximes

2021

Adv Synth Catal

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Radical cascade cyclization of β,γ‐unsaturated hydrazones/oximes has recently emerged as an efficient and powerful protocol for the construction of diverse and valuable functionalized pyrazolines and isoxazolines. In this review, three catalytic ways of radical cascade cyclization of β,γ‐unsaturated hydrazones/oximes are summarized and classified; these are transition‐metal‐catalyzed systems, transition‐metal‐free systems, and photo‐/electrocatalytic systems, respectively. Through these methods, various functional groups are installed on the pyrazoline and isoxazoline skeletons to enrich the small organic molecule library.

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Section: Radical Strategies For Cyclization Of βγ‐Unsaturated Hydrazones and Oximesmentioning

confidence: 99%

Radical Cascade Reactions of β,γ‐Unsaturated Hydrazones/Oximes

2021

Adv Synth Catal

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“…In many instances, these methods not only require the use of transition metal catalysts, high temperature or toxic, costly, organic or inorganic oxidizing agents but also suffer from low to moderate yields. However, progress in the oxyhalogenation reaction has been made recently and examples include Pd, [15a] Fe [15b] Cu, [15c] or Al [15d] or TBHP [15e] mediated protocols. Further‐more, molecular bromine was applied in the cyclization, albeit with varying yields and the observation of side reactions [15f] .…”

Section: Figurementioning

confidence: 99%

Intramolecular Electrochemical Oxybromination of Olefins for the Synthesis of Isoxazolines in Batch and Continuous Flow

et al. 2021

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A highly regioselective protocol for the synthesis of isoxazolines through cascade CÀ O and CÀ Br bond formation has been developed. The electrochemical approach uses traceless electrons as a sole source of oxidant, thus avoiding the use of stoichiometric organic or inorganic oxidants and provides a mild and environmentally benign alternative pathway for the synthesis of a wide range of valuable substituted isoxazolines from alkenyl oximes in good yields. Synthetic organic chemistry is considered a fast-developing field in science as it continuously provides new routes towards the synthesis of novel materials via green, sustainable, and economical techniques. [1,2] Electrochemical synthetic methods have gained increasing attention since they provide mild conditions, good functional group tolerance, high regioselectivity and chemoselectivity, and reduced waste by avoiding costly oxidants or reductants in favor of electricity. [3] Nitrogen-containing heterocycles are important building blocks and part of many commercial products. Among them, isoxazolines are an important class of heterocyclic compounds and their derivatives are frequently found in a wide range of natural products, biologically active compounds, agrochemicals, and pharmaceuticals. [4,5] (Figure 1) Moreover, isoxazolines can serve as versatile synthetic intermediates in organic chemistry. [6][7][8][9][10][11] Therefore, the development of sustainable methods providing isoxazolines and their derivatives remains an important target for synthetic organic chemists. Approaches for their synthesis range from the use of the 1,3-dipolar cycloaddition reactions of nitrile oxides with allyl halide [12,13] to oxyhalogenation of allylic oximes. [14,15] In many instances, these methods not only require the use of transition metal catalysts, high temperature or toxic, costly, organic or inorganic oxidizing agents but also suffer from low to moderate yields. However, progress in the oxyhalogenation reaction has been made recently and examples include Pd, [15a] Fe [15b] Cu, [15c] or Al [15d] or TBHP [15e] mediated protocols. Furthermore, molecular bromine was applied in the cyclization, albeit with varying yields and the observation of side reactions. [15f] Hence, the development of a simple, economically viable, and Communications

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“…Firstly, iminoxyl anion A, formed by deprotonation of substrates 1 were SET oxidized by Cu(II), to generate the iminoxyl radical B. 32 Then, iminoxyl radical B undergoes 5-exo-trig radical cyclization, delivering the carbon-centered radical intermediate C. The addition of the radical C onto the C=C bond of allyl sulfone 2 followed by desulfonation leads to the product 3 and a sulfonyl radical. 45,46 Finally, SET reduction of sulfonyl radical by Cu(I) forms the benzenesulfinic acid anion with the concomitant regeneration of Cu(II).…”

Section: Scheme 4 Gram Scale Reaction and Product Derivatizationmentioning

confidence: 99%

“…28 Although highly practical, the types of oxygen-centered radicals remain limited. Encouraged by the works of Han, 29,30 Wang, 31 and our group 32 on the copper-catalyzed iminoxyl radical-mediated oxyfunctionalization of alkenes, we envisioned that iminoxyl radical may also be involved in the oxyallylation with allyl sulfones. Herein, we describe more convenient method, which has led to the construction of useful isoxazolines [33][34][35][36][37][38][39][40][41][42][43] and the installation of versatile alkenyl groups in one transformation.…”

Section: Introductionmentioning

confidence: 99%

Copper-catalyzed radical oxyallylation of olefins for the construction of alkene-containing isoxazolines

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Qian²,

Dai³

et al. 2021

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General 5-Halomethyl Isoxazoline Synthesis Enabled by Copper-Catalyzed Oxyhalogenation of Alkenes

Abstract: A general and efficient oxyhalogenation of unsaturated ketoximes has been achieved through copper catalysis with diethyl bromomalonate, N-chlorosuccinimide, and N-iodosuccinimide, yielding 5-chloromethyl, 5-bromomethyl, and 5-iodomethyl isoxazolines in good to excellent yields.

Cited by 22 publications

References 29 publications

Radical Cascade Reactions of β,γ‐Unsaturated Hydrazones/Oximes

Radical Cascade Reactions of β,γ‐Unsaturated Hydrazones/Oximes

Intramolecular Electrochemical Oxybromination of Olefins for the Synthesis of Isoxazolines in Batch and Continuous Flow

Copper-catalyzed radical oxyallylation of olefins for the construction of alkene-containing isoxazolines

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