Asymmetric Three-Component Reaction of Enynal with Alcohol and Imine as An Expeditious Track to Afford Chiral α-Furyl-β-amino Carboxylate Derivatives

Herein, we report an achiral dirhodium complex and chiral phosphoric acid cooperatively catalyzed asymmetric three-component reaction of enynal with alcohol and imine, affording chiral alpha-furyl-beta-amino carboxylates in good to high yields with generally excellent stereoselectivity. The successful introduction of enynal as a carbene precursor in this reaction provides an expeditious track to prepare complex furan derivatives with adjacent quaternary and tertiary stereocenters. The starting materials are stable and readily available, and the method features 100% atom economy with high bond-formation efficiency. This is a highly enantioselective gem-difunctionalization reaction of metal carbene generated in situ from enynal. These generated chiral products could be smoothly converted to polycyclic frameworks and drug-conjugated derivatives through different cycloaddition reactions.

Automated summary

An achiral dirhodium complex and chiral phosphoric acid cooperatively catalyze the asymmetric three-component reaction of enynal with alcohol and imine, resulting in the formation of chiral alpha-furyl-beta-amino carboxylates with good to high yields and excellent stereoselectivity. This method efficiently prepares complex furan derivatives with adjacent quaternary and tertiary stereocenters.