Remote stereocontrol in the (4 + 2) cycloadditions of 1,7-zwitterions: Asymmetric synthesis of multifunctionalized tetrahydroquinoline derivatives

Abstract

The scope of stereochemistry recognition usually occurs near the chiral scaffold of a ligand or catalyst. Remote stereocontrol, which can surpass the limits of stereorecognition of remote prochiral centers, has long been a challenging object of great interest in asymmetric catalysis. The current work realized the remote stereocontrol of 1,7-zwitterion intermediates formed from Huang's o-amino aryl MBH carbonates. With simple and easily accessible β-ICD as the bifunctional catalyst, multifunctionalized tetrahydroquinoline derivatives could be synthesized via (4 + 2) cycloadditions with excellent enantioselectivity and diastereoselectivity under mild conditions. The strategy possesses broad substrate scope, and three types of electron-deficient enones are successfully applied. Mechanistic studies disclosed the Lewis base-catalyzed reaction pathway, and H-bonding between the catalyst and enones is crucial for long-range stereocontrol. Scale-up reaction and transformations of the tetrahydroquinoline products demonstrated the potential of this strategy.