Mass Spectrometric Screening of Racemic Amine Catalysts for Enantioselective Michael Additions

In extension of a concept of Lloyd-Jones, based on the combination of a racemic catalyst with a scalemic substrate, we have recently developed a method for determining the enantioselectivity of a chiral catalyst from its racemic form by mass spectrometric screening of a non-equal mixture of two mass-labeled quasi-enantiomeric substrates. After an initial proof of principle using Pd-catalyzed allylic substitution as test reaction, we report now the successful application of this approach to the screening of chiral amines as catalysts for the enantioselective Michael addition to a,b-unsaturated aldehydes. The results confirm that our method allows fast and reliable evaluation of chiral racemic catalysts. This opens up new possibilities for investigating catalyst structures that are not easily available in enantiomerically pure form.