Abstract
Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and 1H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second‐order rate constants for general‐base‐catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.
Highlights
Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited
To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and 1H NMR spectroscopy
We show that rate constants for racemization correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations
Summary
International Edition: DOI: 10.1002/anie.201709163 German Edition: DOI: 10.1002/ange.201709163 Andrew Ballard, Hiwa O. Ahmad, Stefania Narduolo, Lucy Rosa, Nikki Chand, David A. Cosgrove, Peter Varkonyi, Nabil Asaad, Simone Tomasi, Niklaas J. Buurma,* and Andrew G. Leach*
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