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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Enantioselective Synthesis of Spirocyclic γ-Lactams Featuring Dual Central and N-N Axial Chirality via
Wenkai Li1, Pengfei Jia1, Ke Yang1
1State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian116024, P. R. China.
Abstract:
Co/salicyloxazoline (Salox)-catalyzed asymmetric C-H activation/spiro annulation is reported for the synthesis of spirocyclic γ-lactams with dual N-N axial and spiro-central chirality. Through an enantioselective desymmetrization protocol of the prochiral maleimide, products are obtained in yields of 34-62% with up to 95% ee and >20:1 dr. Axial chirality established during C-H activation directs subsequent enantioselective spiro-center formation. This protocol accommodates bioactive scaffolds, providing streamlined access to complex chiral N-heterocycles.
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