H-Bond Donor-Directed Switch of Diastereoselectivity in the Enantioselective Intramolecular Aza-Henry Reaction of Ketimines.

ABSTRACT

We report an H-bond donor controlled diastereoselective switchable intramolecular aza-Henry reaction of ketimines derived from α-ketoesters and 2-(2-nitroethyl)anilines, allowing facile access to chiral tetrahydroquinolines bearing an aza-quaternary carbon stereocenter, which are privileged scaffold for medicinal researches. While newly developed cinchona alkaloid derived phosphoramide-bearing quaternary ammonium salt C2 selectively give cis-adducts in up to 201 dr and 99% ee, the corresponding urea-bearing analogue C8 preferentially give trans-adducts in up to 201 dr and 99% ee.