- Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides
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Herein we report a method for the synthesis of 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as O-imidoylation or hetero [3 + 2]-cycloaddition. The reaction happens fast in water and completes within 1-2 hours, which provides an environmentally friendly access to 3,4,5-trisubstituted isoxazoles, an important class of structures found in numerous bioactive natural products and pharmaceuticals. Additionally, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl chlorides to form furoxans also known as 1,2,5-oxadiazole 2-oxides, a class of structures with important biological activities due to their unique electronic nature and coordination ability.
- Hossain, Md Imran,Khan, Md Imdadul H.,Kim, Seong Jong,Le, Hoang V.
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p. 446 - 458
(2022/05/18)
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- Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
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The current study aimed to design and synthesize a novel series of fluorophenyl-isoxazole-carboxamide derivatives and evaluate their antiproliferative activities. Anticancer activities of the novel compounds were evaluated by MTS assay against four cancer
- Abualhasan, Murad,Amer, Johnny,Ayaseh, Aseel,Hawash, Mohammed,Ibrahim, Sameeha,Issa, Shahd,Jaradat, Nidal,Levent, Serkan,Mousa, Ahmed,Shtayeh, Tahrir
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p. 855 - 863
(2021/09/06)
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- Enolate-mediated 1,3-dipolar cycloaddition reaction of β-functionalized ketones with nitrile oxides: Direct access to 3,4,5-trisubstituted isoxazoles
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TMG-catalyzed [3 + 2] organocatalytic 1,3-dipolar cycloaddition reactions of β-functionalized ketones with nitrile oxides have been developed. This strategy could generate 3,4,5-trisubstituted isoxazoles in high yields and regioselectivities.
- Zhou, Xiao,Xu, Xianhong,Shi, Zhenyan,Liu, Kun,Gao, Hua,Li, Wenjun
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supporting information
p. 5246 - 5250
(2016/07/06)
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- Synthesis method of 3,4,5-trisubstituted isoxazole type compound
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The invention discloses a synthesis method of a 3,4,5-trisubstituted isoxazole type compound. In reaction solvent, the 3,4,5-trisubstituted isoxazole type compound is obtained through reaction with substituted acetoacetamide and chloro-substituted aldoxim
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Paragraph 0017
(2016/10/09)
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