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DOI: 10.1055/s-0029-1220138
Regioselective Synthesis of Phosphonyl Pyrazoles
K. Mohanan, A. R. Martin, L. Toupet, M. Smietana*, J.-J. Vasseur
Université Montpellier 1, Université Montpellier 2 and Université de Rennes, France
Publication History
Publication Date:
22 June 2010 (online)
Significance
Based on a previous one-pot synthesis of triazoles from aldehydes using the Bestmann-Ohira reagent 3 (D. Luvino et al. Synlett 2007, 3037), the synthesis of substituted 5-phosphonyl pyrazoles 4 by a three-component (aldehydes, cyanoacetic derivatives, and 3) domino Knoevenagel condensation-formal 1,3-dipolar cycloaddition sequence has been developed. A range of aldehydes 1 and cyanoacid derivatives 2 afforded 4 in good to excellent yields (cyanoacetic derivatives, e.g. phenylbutyronitrile, benzylcyanide, and trimethylsilylacetonitrile give the homologated alkyne). The structure of 4 was confirmed by single crystal X-ray analysis. A mechanism is proposed involving Michael-type addition of B on the Knoevenagel product A resulting in the intermediate C. C undergoes cyclization to the pyrazoline D and thence affords 4 after HCN elimination and intramolecular proton transfer.