The preparation of new 4-bromo-2,3-dihydroisoxazoles and their utilization in the synthesis

Authors: Lucia Kleščíková 1    Róbert Fischer 1    Ľubor Fišera 1   
1 Fakulta chemickej a potravinárskej technológie, STU, Bratislava,   
Year: 2014
Section: Organic, bioorganic and pharmaceutical chemistry, pharmacology
Abstract No.: 1025
ISBN: 978-80-970712-6-4

2,3-Dihydroisoxazoles represent very interesting compounds for their versatile applications in organic synthesis.[1-3] They are prepared either by 1,3-dipolar cycloadditions of nitrones with alkynes [4] directly or in two step-synthesis, involving intramolecular cyclization of the corresponding N-hydroxylamines.[5-7] On the other hand, 4,5-unsubstituted 2,3-dihydroisoxazoles can be obtained from readily available 5-acetoxyisoxazolidines under mild elimination conditions (TMSOTf, BSTFA, NMP).[8]

In line our present work, we focused the interest on searching for efficient reaction conditions, in order to synthesise novel 4-bromo-2,3-dihydroisoxazoles as potential building blocks in medicinal chemistry and to apply them in the halogen/metal exchange reactions. Intermediate lithium-isoxazolidines were subsequently “in situ” coupled with various electrophiles. The preparation of the starting 2,3-dihydroisoxazoles, their halogenations and the synthesis of new 4-substituted-2,3-dihydroisoxazoles will be presented.

The authors gratefully thank the Slovak Grant Agencies (APVV, Bratislava, project No. APVV-0203-10; VEGA project No. 1/0488/14 and ASFEU, Bratislava, ITMS project No. 26240120001, 26240120025).
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