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Enantioselective protonation

Nature Chemistry volume 1, pages 359–369 (2009)Cite this article

Abstract

Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods for achieving enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proved useful for the preparation of a number of valuable organic compounds. Here, we review recent reports of enantioselective protonations, classifying them according to mechanism, and discuss how a deeper understanding of the processes can lead to improved methods for effecting this most fundamental method of obtaining enantiopure compounds.

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Figure 1: Enantioselective tautomerization of an isolated enol.
Figure 2: Enzyme-catalysed enantioselective protonation reactions.
Figure 3: Enantioselective protonations by means of stoichiometric chiral Brønsted acids.
Figure 4: Enantioselective protonations by means of catalytic chiral Brønsted acids.
Figure 5: Enantioselective protonations by means of catalytic chiral Brønsted acids.
Figure 6: The use of nucleophilic heterocycle catalysts to generate chiral proton acceptors.
Figure 7: Conjugate addition/protonation sequences catalysed by chiral metal complexes.
Figure 8: Transition metal-catalysed enantioselective protonation reactions by means of chiral metal enolates.
Figure 9: Radical conjugate addition followed by enantioselective H-atom transfer.

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Acknowledgements

We thank the National Institutes of Health, National Institute of General Medical Sciences (grant number R01GM080269<0x2011>01), Eli Lilly (predoctoral fellowship to J.T.M.), Amgen, Abbott Laboratories, Boehringer Ingelheim, Merck, Bristol-Myers Squibb and the California Institute of Technology for financial support.

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  1. Department of Chemistry and Chemical Engineering, The Arnold and Mabel Beckman Laboratories of Chemical Synthesis, California Institute of Technology, 1200 East California Boulevard, Mail Code 164-30, Pasadena, 91125, California, USA

    Justin T. Mohr, Allen Y. Hong & Brian M. Stoltz

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Mohr, J., Hong, A. & Stoltz, B. Enantioselective protonation. Nature Chem 1, 359–369 (2009). https://doi.org/10.1038/nchem.297

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