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: Base-mediated and Keto-enol-controlled Mechanism (original) (raw)
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Beilstein Journal of Organic Chemistry
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...
A Convenient Synthetic Method of Isoxazole Derivatives Using Copper(II) Nitrate
HETEROCYCLES, 2014
3-Acetylisoxazoles were synthesized by the reaction of alkenes or alkynes in acetone as solvent with copper(II) nitrate and formic acid. In the case of ethyl acetate as solvent, 3-benzoylisoxazoles were yielded by the reaction of alkynes and acetophenone with copper(II) nitrate and nitric acid. This synthetic method provides a convenient production of isoxazole derivatives.
One-Pot Copper(I)-Catalyzed Synthesis of 3,5-Disubstituted Isoxazoles
The Journal of Organic Chemistry, 2005
Disubstituted isoxazoles are obtained in good yields by a convenient one-pot, three-step procedure utilizing a regioselective copper(I)-catalyzed cycloaddition reaction between in situ generated nitrile oxides and terminal acetylenes. Most functional groups do not interfere with the reaction, which can be performed in aqueous solvents without protection from oxygen. Since all reagents are used in stoichiometric amounts, formation of byproducts is minimized.
Synthesis of isoxazole conjugates of sugars via 1,3-dipolar cycloaddition
Canadian Journal of Chemistry, 2008
Isoxazole conjugates of sugar have been synthesized by the aid of 1,3-dipolar cycloaddition in a click chemistry approach. The sugar-derived propargyl ethers underwent 1,3-dipolar cycloadditions smoothly with in situ generated nitrile oxides from aromatic oximes in good yields. The reaction exhibited a high degree of regioselectivity.Key words: isoxazole conjugates, 1,3-dipolar cycloadditions, nitrile oxides.