Sequential Relay Catalysis in a Multicomponent [4 + 1] Cycloaddition for the Synthesis of Highly Functionalized Pyrazoles

Abstract We report a Sc(OTf)3/AgOAc relay-catalyzed multicomponent [4 + 1] cycloaddition cascade for the efficient synthesis of polysubstituted pyrazoles 5–6 from sulfoxonium ylides, vinyl diazo esters, and vinylene carbonates or maleimides. Although vinyl diazo esters have been widely used as C1 and three-atom synthons, their application as four-atom (C2N2) building blocks remains underexplored. This bimetallic relay strategy features well-defined and complementary catalytic roles: Sc(III) promotes pyrazole ring assembly, whereas Ag(I) facilitates sequential alkene functionalization while suppressing undesired side reactions. The one-pot cascade proceeds under ambient conditions with excellent step economy, forms three new chemical bonds in a single operation, and affords structurally diverse pyrazoles with good functional-group tolerance. Mechanistic studies support the proposed relay catalytic pathway. The reaction is readily scalable to gram scale, providing a modular and practical approach to the rapid synthesis and late-stage diversification of biologically valuable pyrazole derivatives.