Measurement of Enantiomeric Excess by Kinetic Resolution and Mass Spectrometry**

The powerful nature of combinatorial synthetic methods for the preparation of diverse libraries of small molecules has often made the analysis of such compounds the rate-limiting step in their application.[1] An intriguing target is the discovery of new enantioselective catalytic processes by the testing of large numbers of candidate catalysts.[2] Optimal use of combinatorial synthesis in this endeavor will require the high-throughput measurement of enantiomeric excesses on a small scale, a task for which current techniques are evolving.[1, 3] We describe here a method for the determination of enantiomeric excesses of alcohols and amines on the nanomole scale by diastereoselective derivatization and automated quantitative electrospray ionization mass spectrometry (ESIMS).[4, 5] The capabilities of mass spectrometry for the analysis of component mixtures[4, 6] allows the chemical procedures and reagents used here to be simple and generally applicable. The technique employs an equimolar mixture of pseudoenantiomeric amass-taggedo chiral acylating agents that differ in a substituent remote to the chiral center, such that the mass of the molecule is correlated to its absolute configuration. In general, the reactions of the enantiomers of any pair of chiral reagents will proceed with nonequal rate constants (kf> ks ; fˆ fast, sˆ slow),[7] as shown in Scheme 1 for the reaction of