Mass Spectrometric Back Reaction Screening of Quasi-Enantiomeric Products as a Mechanistic Tool

In this account, we discuss a mass spectrometric method that enables unambiguous identification of intermediates involved in the enantioselective step of a catalytic cycle. This method, which we originally developed for rapid evaluation of chiral catalysts, is based on monitoring the back reaction of mass-labeled quasi-enantiomeric products by ESI-MS. In this way, the intrinsic enantioselectivity of a chiral catalyst can be determined directly by quantification of catalytically relevant intermediates. By comparing the results from the forward and back reaction, direct evidence for the involvement of a catalytic intermediate in the enantioselective step can be obtained. In addition, insights about the energy profile of the catalytic cycle may be gained. The potential of back reaction screening as a mechanistic tool is demonstrated for organocatalytic aldol reactions, 1,4-additions of aldehydes to nitroolefins, Diels-Alder reactions, Michael additions, and Morita-Baylis-Hillman reactions.