Organic and Inorganic Chemistry

A new efficient and safe method for inversion of configuration of chiral amines has been developed.Several homochiral amine synthons were synthesized. Two of them (Cinacalcet and Rivastigimine) were converted into di-tosyl and di-mesyl derivatives. Inversion of configuration of the chiral center was achieved by substitution of the disulfonimide moiety using NaN3 under flow conditions to give an organic azide. The reaction has been fully optimized (temperature, flow rate and solvent) in a flow reactor, which ensured the safety of the whole process. The organic azides were obtained in satisfactory yields and over 90% ee. The azides could be reduced to the desired amines by standard hydrogenation, which should also be achievable under flow conditions. We also intend to expand the method to other amines to make it as widely applicable as possible.