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

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 beta-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. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.