Enantioselective amination of 4-substituted pyrazolones catalyzed by oxindole-containing thioureas and by a recyclable linear-polymer-supported analogue in a continuous flow process

Abstract

A highly efficient organocatalytic amination of 4-substituted pyrazolones with azodicarboxylates mediated by a novel quinine-derived thiourea with a 3,3-diaryl-oxindole scaffold is reported. This synthetic method furnished 4-amino-5-pyrazolones in high yields and with excellent enantioselectivities (up to 97:3 er) at room temperature in short reaction times. Moreover, a linear-polymer-supported bifunctional thiourea, synthesized by reacting a bifunctional aromatic monomer (biphenyl) with isatin in superacidic media and further derivatization, was proven to be also an efficient heterogeneous organocatalyst for this α-amination reaction. The practical value of this process was demonstrated by the use of the immobilized catalyst in recycling experiments, maintaining the activity without additional reactivation, and in flow processes, allowing the synthesis of 4-amino-pyrazolone derivatives in a gram scale with high yield and enantioselectivity.