Is the E/Z Iminium Ratio a Good Enantioselectivity Predictor in Iminium Catalysis?

ABSTRACT

Developing new enantioselective reactions is an important part of chemical discovery but requires time and resources to test large arrays of potential reaction conditions. New techniques are required to analyse many different reactions quickly and efficiently. Mass spectrometry is a high-throughput method; when combined with ion-mobility spectrometry, this technique can monitor diastereomeric reaction intermediates and thus be a handle to study enantioselective reactions. Through this technique and others, it was noted before that in the organocatalytic 1,4-addition to α,ß-unsaturated aldehydes, the abundance of initial diastereomeric intermediates correlates strongly to that of the final enantiomeric products. This work determines isomeric abundance for various catalysts and aldehydes and uses it to predict the enantiomeric excess of two control reactions. The prediction matches well for one reaction but does not predict the obtained results for the second. This finding confirms that the E/Z ratio of the iminium intermediates can be used as a predictor for some reactions, but the kinetics of the following steps can dramatically change the true enantioselectivity.