Dynamic Kinetic Resolution of Primary Amines

Significance

Kinetic resolution employing enzymes is a simple way to obtain enantiomerically pure amines from racemic starting mixtures. Its usability, however, is diminished by the fact that the maximum achievable yield is 50%. The in situ racemization of the undesired enantiomer in a dynamic kinetic resolution overcomes this limitation. In this paper, the authors present a method, which allows for the racemization of unfunctionalized amines, of which previously only one single example has been published (M. Reetz et al. Chimia 1996, 50, 668-669). The racemization takes place via imine formation from the chiral amine and subsequent hydrogen re-addition to yield the amine again, catalyzed by a cyclopentadienyl-derived ruthenium complex. The following highly enantioselective acylation is mediated by commercially available Candida Antarctica lipase B (CALB, Novozym 435), utilizing isopropyl acetate as acylating agent. The reaction tolerates several functional groups, including fluorine, bromine, ether, and tri­fluoromethyl, and it also allows the use of aliphatic amines, which cannot be easily obtained by many other methods.