期刊
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
卷 18, 期 -, 页码 446-458出版社
BEILSTEIN-INSTITUT
DOI: 10.3762/bjoc.18.47
关键词
environmentally friendly; furoxans; 1,2,5-oxadiazole 2-oxides; trifluoromethyl-substituted isoxazoles; 3,4,5-trisubstituted isoxazoles
资金
- American Association of Colleges of Pharmacy
- National Institute of General Medical Sciences [P30GM122733]
- Department of BioMolecular Sciences at the Univer-sity of Mississippi, School of Pharmacy
Here, we report a method for synthesizing 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature. This method provides an environmentally friendly access to these important structures found in bioactive natural products and pharmaceuticals.
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, beta-ketoesters, or beta-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as 0-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.
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