Mantis-shaped chiral pyridine-N-oxides: a new class of ligands in asymmetric palladium(II)-catalysed Friedel-Crafts alkylation

Abstract

Pyridine-type chiral ligands were renowned for their versatility and efficacy in numerous metal-catalyzed asymmetric transformations. To further expand the chiral pyridine-type ligand library, herein, we prepared mantis-shaped pyridine-NO ligands endowed with tricyclic pyrroloimidazolone-derived chiral N-oxide as the key stereodirecting and coordinating monochiral arm from the conformationally rigid bicyclic prolinamides in operationally simple two steps and up to 62% overall yield. The catalytic activity of the novel mantis-shaped pyridine-NO ligand L1 (tricyclic pyrroloimidazolone-derived chiral pyridine-N-oxide ligand) was evaluated in the asymmetric Friedel-Crafts alkylation reaction of indoles. The desired products were obtained with up to 92% yield and 99% ee with a low loading % of the L1a-Pd(II) complex generated in situ from L1a and Pd(OAc)2. The stereoelectronic property of the chiral ligand L1 could be regulated by changing the structure of aromatic rings on the amide group. Experiments demonstrated that the counteranion is involved in the stereoselectivity-determining step in this soft palladium(II) catalysis.