Details

Autor(en) / Beteiligte

• Hilgers, Roelant
• Yong Teng, Sin
• Briš, Anamarija
• Pereverzev, Aleksandr Y.
• White, Paul
• Jansen, Jeroen J.
• Roithová, Jana

Titel

Monitoring Reaction Intermediates to Predict Enantioselectivity Using Mass Spectrometry

Ist Teil von

• Angewandte Chemie International Edition, 2022-09, Vol.61 (36), p.e202205720-n/a

Auflage

International ed. in English

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Enantioselective reactions are at the core of chemical synthesis. Their development mostly relies on prior knowledge, laborious product analysis and post‐rationalization by theoretical methods. Here, we introduce a simple and fast method to determine enantioselectivities based on mass spectrometry. The method is based on ion mobility separation of diastereomeric intermediates, formed from a chiral catalyst and prochiral reactants, and delayed reactant labeling experiments to link the mass spectra with the reaction kinetics in solution. The data provide rate constants along the reaction paths for the individual diastereomeric intermediates, revealing the origins of enantioselectivity. Using the derived kinetics, the enantioselectivity of the overall reaction can be predicted. Hence, this method can offer a rapid discovery and optimization of enantioselective reactions in the future. We illustrate the method for the addition of cyclopentadiene (CP) to an α,β‐unsaturated aldehyde catalyzed by a diarylprolinol silyl ether. Diastereomeric intermediates can be separated by ion mobility mass spectrometry. Monitoring of the kinetics of the intermediates allows the prediction of the overall reaction enantioselectivity. The experiments can be performed in a small scale and do not require an isolation of the products.