Catalytic Racemisation of Chiral Amines and Application in Dynamic Kinetic Resolution

A mild and efficient procedure for the racemisation of optically active amines has been developed and applied to the dynamic kinetic resolution (DKR) of a racemic amine. Pentamethylcyclopentadienyliridium (III) iodide dimer dissolved in a convenient solvent is the precatalyst that reacts in situ with primary, secondary, or tertiary amines to form what we have named a SCRAM catalyst. This is able to dehydrogenate a substrate amine to form an imine, which, depending upon the reaction conditions, is then reduced back to the amine. When an optically active amine is mixed with the iridium precatalyst, racemisation is observed. The SCRAM catalyst is used under mild conditions compatible with suitable enzymes and acyl donors, and thus the DKR of an amine has been effected, giving significantly higher yield than if the enzyme alone was used. A mixed carbonate was identified as the optimal acyl donor, giving a carbamate product that is readily removed by acidic hydrolysis.