Intramolecular Copper-Catalyzed Asymmetric Propargylic [4+2]-Cycloaddition toward Optically Active Tetrahydroisoindolo[2,1-a]quinoxalines

An intramolecular Cu-catalyzed asymmetric propargylic [4 + 2] cycloaddition of bis-N-nucleophile-functionalized propargylic esters has been realized in the support of a chiral tridentate N-ligand, (S,S)-Pybox-diOAc, leading to chiral tetrahydroisoindolo[2,1-a]quinoxalines in high yields and with good to excellent enantioselectivities. The reaction features high efficiency, simplicity, and broad substrate scope, thus providing a powerful and concise strategy for stereoselective access to optically active polycyclic heterocycle frameworks that are otherwise difficult to synthesize.

Automated summary

In this study, an intramolecular Cu-catalyzed asymmetric propargylic [4 + 2] cycloaddition reaction was achieved using a chiral tridentate N-ligand as the catalyst, leading to chiral tetrahydroisoindolo[2,1-a]quinoxalines with high yields and good to excellent enantioselectivities. The reaction is efficient, simple, and has a broad substrate scope, providing a powerful and concise strategy for the stereoselective synthesis of optically active polycyclic heterocycle frameworks.