Regioselective synthesis of bifunctional tridentate mantis-BPy-OPI-2NO ligands: empowering asymmetric addition of indoles

Abstract

Can chiral tertiary amine-derived N-oxide ligands that incorporate a pyridine N-oxide moiety provide enhanced stereocontrol in asymmetric transformations? To address this issue, herein, we first report a regioselective synthesis of a series of new mantis-shaped bifunctional tridentate chiral BPy-OPI-2NO ligands by incorporating a bipyridine N-oxide group into a tertiary amine-derived N-oxide scaffold. These new bifunctional ligands allowed two N-oxides to act as the chelating sites for coordination with Earth-abundant metals, and a pyridine N-oxide moiety as a hydrogen-bonding acceptor, thus cooperatively activating both nucleophiles and electrophiles, exhibiting superior performance in the asymmetric addition of indoles to 2,3-dioxopyrrolidines, which provided a variety of chiral indole derivatives in 85–92% yield and up to 99% ee.