Construction of Enantioenriched γ,γ-Disubstituted Butenolides Enabled by Chiral Amine and Lewis Acid Cascade Cocatalysis

Herein we report a cascade cocatalysis strategy for the facile construction of chiral gamma,gamma-disubstituted butenolides. The synthetic manifold employs simple alkynoic acids instead of the preformed silyloxy furans or 5-substituted furan-2(3H)-ones. In situ formed 5-substituted furan-2(3H)-ones by AgNO3 or Ph3PAuCl/AgOTf catalyzed cyclization of alkynoic acids can smoothly engage in the subsequent chiral diphenylprolinol TMS-ether catalyzed Michael and Michael-aldol reactions. The cascade process serves as a general approach to chiral quaternary gamma,gamma-disubstituted butenolides.

Automated summary

This method utilizes a cascade cocatalysis strategy to achieve the easy construction of chiral gamma, gamma-disubstituted butenolides, showing good generality and effectiveness.