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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #383377
Research Project: Biobased Pesticide Discovery and Product Optimization and Enhancement from Medicinal and Aromatic Crops

Location: Natural Products Utilization Research

Title: Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3+2]-cycloaddition of nitrile oxides and 1,3-diketones, ß-ketoesters, or ß-ketoamides: Base-mediated and keto-enol-controlled mechanism.

Author
item HOSSAIN, MD IMRAN - University Of Mississippi
item KHAN, MD IMDADUL - University Of Mississippi
item Kim, Seong
item LE, HOANG - University Of Mississippi

Submitted to: Beilstein Journal of Organic Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/8/2022
Publication Date: 4/22/2022
Citation: Hossain, M., Khan, M.H., Kim, S., Le, H.V. 2022. Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3+2]-cycloaddition of nitrile oxides and 1,3-diketones, ß-ketoesters, or ß-ketoamides: Base-mediated and keto-enol-controlled mechanism.. Beilstein Journal of Organic Chemistry. https://doi.org/10.3762/bjoc.18.47.
DOI: https://doi.org/10.3762/bjoc.18.47

Interpretive Summary: Isoxazoles are a privileged class of five-membered heterocycles, which are found in numerous bioactive natural products, and they showed a wide range of biological activities. New synthetic methods to develop efficient, high-yield, and green routes to isoxazoles are always highly desirable. The present study developed a fast, water-assisted synthesis of 3,4,5-trisubstituted isoxazoles at room temperature via a [3+2] cycloaddition between 1,3-diketones and nitrile oxides. This efficient reaction method can be equally applicable for ß-ketoesters and ß-ketoamides. This advanced method is environmentally friendly due to the high yields and fast reaction time in aqueous media. It could be used in the large-scale production of critical 3,4,5-trisubstituted isoxazoles that used antibiotic drugs' precursors.

Technical Abstract: A selective [3+2]-cycloaddition reaction of nitrile oxides and 1,3-diketones, ß-ketoesters, or ß-ketoamides in water without the need of a metal catalyst is described. The selectivity of the reaction can be controlled by the polarity of solvents in an appropriate base. The optimized reaction condition circumvented other reactions, such as O-imidoylation or hetero [3+2]-cycloaddition. The reaction happens fast in water to provide an environment friendly access to 3,4,5-trisubstituted isoxazoles which are an important class of heterocycles found in numerous bioactive natural products and pharmaceuticals.