A Efficient Five-step One-pot Synthesis of 4-[(arylamino)methyl]-5-aryl-3-carboxyethyl-isoxazoles from β-enamino diketones

Isoxazoles derivatives have attracted widespread attention of chemists, mainly because of interesting biological and pharmacological properties.1-3 Most notably, isoxazoles functionalized with an additional nitrogen-containing group is usually associated with potent pharmaceutical agents.2,3Therefore, the development of synthetic methodologies for access these derivatives is still an active area in the organic synthesis research. In this context, based on studies reported by our research group,4 we developed in this work a simple and efficient five-step one-pot methodology for the preparation of 4-[(arylamino)methyl]-5-aryl-3-carboxyethyl-isoxazoles (6a-e) from the β-enamino diketone (2a) and hydroxylamine substrates. The synthetic steps involved in this methodology are based on the following transformations: interconversion of the tertiary β-enamino diketone 1a to the secondary derivative 2a; generation of the intermediate iminium salt 3a from the cyclocondensation of 2a with hydroxylamine assisted by BF3.OEt2, transimination of 3a to 5a-e and, finally, reduction of 5a-e to the desired products 6a-e.