Catalytic Asymmetric Direct and Vinylogous Aldol, Michael and Alkylation Reactions

Abstract

Pyrazoles and pyrazolones are a highly explored and privileged class of aza-heterocycles with a wide range of applications, thereby rendering a recurring interest in their synthesis and functionalization. Majority of the reactions, developed till date involve pyrazoline-5-ones as nucleophiles. With the application of pyrazole-4,5-diones, another mode of reactivity has emerged, wherein pyrazolones act as electrophiles. In this chapter, enantioselective aldol reaction of 3-acetyl- 2H-chromen-2-ones to pyrazole-4,5-diones has been demonstrated. Using bifunctional tertiary amino-amide as catalyst, the products, containing an oxygen-containing quaternary stereogenic center and two biologically important heterocyclic frameworks, were obtained in good yields with high enantioselectivities. This is also one of the few reactions which explored the C-4 electrophilicity of pyrazolones, rather than the usually established C-4 nucleophilicity. The reaction has a broad substrate scope and substitutions on both coumarin ring and pyrazole-4,5-diones were generally well tolerated.