Monodentate/bidentate chiral Ph/Py-NO ligands: an unexpected switch of enantioselectivity in Friedel–Crafts alkylation of indoles and 2,3-dioxopyrrolidines

Abstract

The development of single chiral source-derived ligands to fine-switch enantioselectivity has continuously attracted the attention in asymmetric catalysis. Herein, we use the same chiral source L-prolinamide as the starting material to synthesize chiral bidentate pyridine-type N-oxide ligands (denoted as Py-NO) and chiral monodentate phenyl N-oxide ligands (denoted as Ph-NO); their effectiveness was demonstrated in the switch of enantioselectivity in palladium(II)-catalysed Friedel–Crafts (FC) alkylation of indoles and 2,3-dioxopyrrolidines, and both enantiomers of structurally important indole derivatives can be prepared in good yields (up to 91% yield) and high enantioselectivities (up to 99% ee). Key to the success of the switch of enantioselectivity is the existence of two different activation patterns in this palladium(II) catalytic system. Experiments demonstrated that a counteranion would plausibly coordinate to the palladium(II) center in the stereoselectivity-determining step. Preliminary mechanistic studies provide a rational explanation for the above observations. This study is the first example of a monodentate ligand in asymmetric catalytic Friedel–Crafts alkylation.