Synfacts 2011(9): 0945-0945  
DOI: 10.1055/s-0030-1260994
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Isoxazoles from the Reaction of Nitroalkanes with Oxetanes

Contributor(s): Victor Snieckus, Emilie David
J. A. Burkhard, B. H. Tchitchanov, E. M. Carreira*
ETH Zürich, Switzerland
Further Information

Publication History

Publication Date:
19 August 2011 (online)


Reported is the synthesis of 3-substituted isoxazole 4-carboxaldehydes from the condensation of nitroalkanes 1 with 3-oxetanone (2) under basic conditions. Whereas the use of primary amines, such as benzylamine, leads to the conjugated addition product 4, treatment of 1 and 2 with secondary or tertiary amines gave the unexpected rearrangement product 3. The reaction is proposed to proceed by Henry condensation to the nitroalkene 5, which, upon rearrangement shown (Hünig’s base is most effective) leads to 3. Steric effects are assumed to control conjugate addition favoring the deprotonation of 5. The resulting oxetene 6 undergoes a ring opening to form the intermediate 7, which upon dehydration affords 3.