Towards the Deracemization of Cyclic Tertiary Amines Enabled by Photoredox Catalysis

Abstract

The need for enantiopure chiral compounds is ubiquitous in the pharmaceutical and agrochemical industries, and often it is more cost effective to resolve a racemic mixture than to make these compounds in an enantioselective fashion. Deracemization of a racemic mixture is a promising alternative to classical and kinetic resolutions, which are heavily utilized in industry despite having maximum theoretical yields of only 50%. To date, most deracemizations reported have used the chemical energy of stoichiometric amounts of oxidants and reductants to drive forward the reaction, and fully catalytic deracemizations are incredibly rare. The Knowles lab has shown that deracemization of chiral cyclic ureas can be effected using a system that uses photocatalysis to harnesses the energy of light to drive deracemization and that is catalyzed by chiral thiol, chiral phosphate, and an iridium photocatalyst. This work seeks to expand the substrate scope to the enantioenrichment of tertiary amines. Conditions were first developed for the racemization of cyclic tertiary amines, and slight enantioenrichment was found in deracemization trials. Proof of concept for the fully catalytic deracemization of this substrate class was obtained. With further development of the enantioenrichment, this reaction may provide an environmentally friendly alternative to commonly used resolutions of cyclic tertiary amines.