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Updated: Oct 21, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Sequential Relay Catalysis in a Multicomponent [4 + 1] Cycloaddition for the Synthesis of Highly Functionalized
Qin Luo1, Yi-Ting Wang1, Meng-Zhen Wei1
1Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming650091, P. R. China.
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.
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