Divergent Cascade Construction of Skeletally Diverse “Privileged” Pyrazole-Derived Molecular Architectures

A powerful divergent cascade strategy has been explored for the easy construction of diverse enantioenriched pyrazole-derived scaffolds from readily available chiral fused pyrazole-tetrahydropyran acetals. These versatile intermediates can react in various ways to give Michael–aldol, reduction–lactonization, α-hydroxylation–acetalization–oxidation, and Wittig–aldol and Wittig–oxa-Michael cascade reactions. Using only six simple building blocks, these processes gave five distinct molecular architectures. Furthermore, screening 10 compounds representing the 5 distinct scaffolds revealed potent anticancer lead compounds that deserve further development.