Development of Eagle-Shaped BPE/Phe-2NO Ligands: Switch of Enantioselectivity in Friedel–Crafts Alkylation

The development of single chiral source-derived ligands to fine-switch enantioselectivity has been a key aspect in asymmetric catalysis. Herein, in this study, using the same chiral source l-prolinamide as the starting material, we synthesize 14 new diphenyl ether bridged C₂-symmetric rigid chiral tertiary amine-derived dioxide ligands (abberviated as BPE-2NO) and 9 new m-phenylene bridged C₂-symmetric rigid chiral tertiary amine-derived dioxide ligands (abberviated as Phe-2NO); their effectiveness was demonstrated in the first switch of enantioselectivity in palladium(II)-catalyzed Friedel–Crafts alkylation. In the presence of palladium acetate as the Lewis acid, both enantiomers of indole derivatives can be prepared in good-to-excellent yields and enantioselectivities by using the single chiral source-derived Eagle-shaped BPE/Phe-2NO ligands. Control experiments and density functional theory calculations provide a rational explanation for the above observations. This study was the first switch of enantioselectivity in palladium(II)-catalyzed Friedel–Crafts alkylation by using the single chiral source-derived ligands.