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Synthesis of Isoxazoles from the Reaction of Nitroalkanes with Oxetanes
J. A. Burkhard, B. H. Tchitchanov, E. M. Carreira*
ETH Zürich, Switzerland
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.