Nanomole-Scale Assignment of Configuration for Primary Amines Using a Kinetic Resolution Strategy

Abstract

The absolute configurations of primary amines were assigned using a kinetic resolution strategy with Mioskowski's enantioselective 1-(R,R) and 2-(S,S) acylating agents. A simple mnemonic was developed to determine the configuration. A pseudoenantiomeric pair of reagents, 1-(R,R) and 2-(S,S)-d(3), was prepared and used to assay primary amines on a micromolar scale. The ESI-MS readout of the resulting acetamide products reproduced the selectivity factors from kinetic experiments. The method can be used on mixtures of amines and was validated with amine samples as small as 50 nmol.