Catalytic Deracemization of 1,2-Aminoalcohols through Enantioselective Hydrogen Atom Abstraction

Catalytic deracemization appears a superficially simple way to obtain enantioenriched chiral compounds but is deceptively challenging. The popularization of photochemical methods which utilize excited state pathways have permitted breakthroughs, but application to simple functional motifs that constitute common chiral building blocks is still rare. We report the catalytic deracemization of <i>N</i>-acyl-1,2-aminoalcohols using a cinchona alkaloid-derived catalyst that operates through enantioselective hydrogen atom abstraction, once oxidized by an excited photocatalyst. In combination with an achiral thiol to return the hydrogen atom, accumulation of the unreactive enantiomer occurs. Our catalyst exhibits extremely high chemoselectivity for abstraction adjacent to alcohols and permits a range of useful functionality to be incorporated into the substrates for deracemization. The method generates versatile small molecule building blocks with very high levels of enantioenrichment and demonstrates the synthetic potential of catalysts able to perform hydrogen atom abstraction in a stereoselective manner.