Chiral Recognizable Host-Guest Interactions Detected by Fast-Atom Bombardment Mass Spectrometry: Application to the Enantiomeric Excess Determination of Primary Amines

Abstract

The enantiomeric excess ( ee) of organic amine compounds has been determined using fast-atom bombardment (FAB) mass spectrometry based on the chiral host–guest complexation systems. The method uses a 1:1 mixture of the given chiral crown ether hosts (HRRRR and HSSSS-dn), one of whose enantiomers is isotopically labeled, for the ee-determination of a given amine salt guest (G+). The peak intensity ratio { I[(HRRRR + G)+] / I[(HSSSS-dn + G)+] = IRIS} of the two diastereomeric host–guest complex ions clearly changes with the change in the ee of the guest. The intensity excess ( Ie) of the two complex ion peaks is newly defined as Ie = ( IRIS −1) / ( IRIS + 1). The two sets of mass spectrometrically obtained Ie values vs a set of ee values of phenylalanine methyl ester and leucine methyl ester hydrochlorides show excellent linear relationships through the zero point ( R2 = 0.9989 and R2 = 0.9970, respectively). This indicates the potential utility of the present ee-determination method to within ± 3% ee. Furthermore, based on the solution equilibrium distributions of the complex ions, the linearity is mathematically justified. Therefore, the ee-determination can be simplified as ee (%) = (| Ie| / | Ie(100)|) × 100: here, Ie(100) is the corresponding Ie value obtained using an enantiomerically pure (100% ee) guest as a reference. The present chiral dimethoxyphenyl crown ether host pairs employed are effective ( IRIS ≥ 1.5) for the ee-determination of most α-amino acid esters, but not effective ( IRIS ≈ 1.0) for most simple alkylamines.