New tertiary amine-derived C2-symmetric chiral pyridine-N,N′-dioxide ligands and their applications in asymmetric catalysis

Abstract

Developing efficient methods for preparing privileged chiral ligands is an important endeavor in synthetic chemistry. Herein, we develop an effective, modular method for the synthesis of tertiary amine-derived C₂-symmetric chiral pyridine-N,N′-dioxides (Py-2NO) from optically pure L-prolinamides/hydroxylprolinamides in operationally simple two steps and up to 62% overall yield. The key to the preparation of these chiral Py-2NO ligands was the regioselective N-oxidation of their corresponding chiral intermediate bis(pyrroloimidazolone)pyridines with m-CPBA. To the best of our knowledge, our work is the first report showing that the amine oxide is trans to the adjacent carboxyamide in chiral N-oxides and is also an unprecedented example of the synthesis of tertiary amine-derived C₂-symmetric chiral pyridine-N,N′-dioxide ligands, expanding the chemical space of chiral N-oxides. The catalytic activity of these novel Py-2NO ligands 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 Py-2NO-Ni(II) complex.