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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

preprint
submitted on 23.03.2021, 14:18 and posted on 24.03.2021, 12:48 by Md Imran Hossain, Md Imdadul H. Khan, Seong Jong Kim, Hoang V. Le
A selective [3+2]-cycloaddition reaction of nitrile oxides and 1,3-diketones, β-ketoesters, or β-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 the presence of an appropriate base. The optimized reaction condition circumvents 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, specifically acyl-substituted, ester-substituted, or amide-substituted isoxazoles, which are important structures found in numerous bioactive natural products and pharmaceuticals.

Funding

Association of Colleges of Pharmacy 2018 New Investigator Award

COBRE Phase III Transitional Center

National Institute of General Medical Sciences

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History

Email Address of Submitting Author

hle@olemiss.edu

Institution

University of Mississippi School of Pharmacy

Country

USA

ORCID For Submitting Author

0000-0002-8392-7113

Declaration of Conflict of Interest

The authors report no conflict of interest.

Version Notes

Communication version

Exports