Efficient Enantioselective Ni(0)-Catalyzed Cascade syn-Arylative Cyclization for Five-Membered Heterocyclics Bearing Chiral Tetrasubstituted Allylic Alcohols
Wanjun Chen , Fei Li , Xinlong Yan , Xu Guo , Rongrong Lv , Tao Zhang , Shaofang Zhou , Guodu Liu
Chinese Journal of Chemistry ›› 2026, Vol. 44 ›› Issue (13) : 2143 -2152.
Enantioselective synthesis of five-membered heterocycles bearing chiral tetrasubstituted allylic alcohols remains challenging due to severe steric hindrance and strict regio- and enantio-control demands. Herein, we report an efficient, highly enantioselective Ni(0)-catalyzed cascade syn-arylative cyclization of hetero-1,6-alkynones with arylboronic acids, enabling direct access to chiral pyrrolidines and tetrahydrofurans with chiral quaternary carbon stereocenters. Using Ni(cod)2/(S)-BIDIME, tert-butanol, and LiOMe, 35 products were obtained in up to 98% yield and >99 : 1 er. Gram-scale synthesis proceeded without erosion of reactivity or enantioselectivity. Mechanistic studies and DFT calculations revealed that the cyclization forming the Ni(II) metallacycle is the enantio-determining step. This work provides a practical strategy for the synthesis of chiral five-membered heterocycles and valuable mechanistic insights for the design of asymmetric catalysts.
Hetero-1,6-alkynones / Ni(0)-catalyzed syn-arylative cyclization / P-chiral ligand / Asymmetric catalysis / Chiral quaternary carbon stereocenters / Arylboronic acids / Five-membered heterocycles / DFT calculations
2026 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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