An effective and general method for the highly regioselective synthesis of 1-phenylpyrazoles from β-enaminoketoesters, tandem Blaise-acylation adducts

An effective and general route for the regioselective synthesis of 1-phenylpyrazoles has been developed from β-enaminoketoesters prepared by tandem Blaise-acylation. This method is applicable to a very broad range of substrates, generating a diverse set of 3-aryl-5-alkyl, 3-alkyl-5-aryl, 3,5-diaryl, and 3,5-dialkyl substituted pyrazoles regioselectively. The dichotomous regioselective synthesis of isotopically discriminated 3-CD ₃-5-CH₃ and 3-CH₃-5-CD₃ substituted pyrazoles showcases the power of this protocol.