Synthesis of Functionalized 4,5-Dihydroisoxazoles Decorated with the Dimethylphosphinoyl Group

Authors

  • Andrii V. Fedyk Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Ukraine
  • Bohdan A. Chalyk Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.23.283988

Keywords:

dimethylphosphine oxide, isoxazoline, dipolar cycloaddition, nitrile oxide, halogenoximes, selectivity, ADME profile

Abstract

Aim. To synthesize a hybrid molecular platform incorporating dimethylphosphinoyl and 4,5-dihydroisoxazole moieties suitable for the creation of focused combinatorial libraries of compounds.
Results and discussion. The base-promoted interaction of halogenoxides with dimethyl(vinyl)phosphine oxide under mild conditions allowed us to obtain 11 isoxazoline–dimethylphosphine oxide hybrids in moderate yields. The reaction was found to be regio- though non-stereoselective. Furoxans were identified as possible side products of the reaction.
Experimental part. The one-pot interaction with dimethyl(vinyl)phosphine oxide was used for the synthesis of the target compounds. Nitrile oxides were obtained in situ from the corresponding halogenoximes by base-promoted generation. The ADME parameters for a synthesized 5-P(O)Me2-isoxazoline compared to its isosters with the same core structure were predicted using a SwissADME Web Tool. The compounds obtained were characterized by 1H, 13C, 19F, 31P NMR spectroscopy and HPLC-MS spectrometry methods, as well as the elemental analysis.
Conclusions. A practical approach to the isoxazoline platform decorated with a 5-P(O)Me2 “magic” group and containing 3-substituent with an easy-to-modify functionality has been developed. On example of the piperidine derivative, the effect of the dimethylphosphinoyl group on physicochemical properties and ADME parameters compared to its isosters has been determined.

Supporting Agency

  • The author received no specific funding for this work.Remove The authors received no specific funding for this work.

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Published

2023-08-30

How to Cite

(1)
Fedyk, A. V.; Chalyk, B. A. Synthesis of Functionalized 4,5-Dihydroisoxazoles Decorated With the Dimethylphosphinoyl Group. J. Org. Pharm. Chem. 2023, 21, 41-52.

Issue

Vol. 21 No. 2 (2023)

Section

Original Researches

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