Beilstein J. Org. Chem.2022,18, 446–458, doi:10.3762/bjoc.18.47
Agriculture, Agricultural Research Service, University of Mississippi, Mississippi 38677, USA 10.3762/bjoc.18.47 Abstract Herein we report a method for the synthesis of 3,4,5-trisubstitutedisoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and
hours, which provides an environmentally friendly access to 3,4,5-trisubstitutedisoxazoles, 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-trisubstitutedisoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl