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Synthesis of 3,5‐Disubstituted Isoxazoles through a 1,3‐Dipolar Cycloaddition Reaction between Alkynes and Nitrile Oxides Generated from O ‐Silylated Hydroxamic Acids
Author(s) -
Carloni LaureElie,
Mohnani Stefan,
Bonifazi Davide
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901045
Subject(s) - chemistry , nitrile , regioselectivity , cycloaddition , combinatorial chemistry , 1,3 dipolar cycloaddition , organic chemistry , catalysis
In this paper, we report the regioselective synthesis of 3,5‐disubstituted isoxazoles by 1,3‐dipolar cycloaddition between alkynyl dipolarophiles and nitrile oxide dipoles generated in‐situ from O ‐silylated hydroxamic acids in the presence of trifluoromethanesulfonic anhydride and NEt 3 . Thanks to the mild, metal‐free and oxidant‐free conditions that this strategy offers, the reaction was successfully applied to a wide variety of alkynyl dipolarophiles, demonstrating the tolerance of this approach to diverse functional groups. In particular, we have shown that the method was compatible with biological molecules such as peptides and peptide nucleic acids (PNA). This protocol constitutes another example of metal‐free 1,3‐dipolar cycloaddition leading to the regioselective formation of isoxazoles.