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Simple protocols for NMR analysis of the enantiomeric purity of chiral primary amines

Nature Protocols volume 3, pages 210–214 (2008)Cite this article

Abstract

A simple three-component chiral derivatization protocol for determining the enantiopurity of chiral primary amines by 1H NMR spectroscopic analysis is described here. The method involves condensation of the amines with 2-formylphenylboronic acid and enantiopure 1,1′-bi-2-naphthol. This approach affords a mixture of diastereoisomeric iminoboronate esters whose ratio can be determined by the integration of well-resolved diastereotopic resonances in their 1H NMR spectra, thus enabling the enantiopurity of the parent amine to be determined easily. The protocol, as described, takes less than 90 min to complete.

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Figure 1: Chiral derivatization protocol used for determining the ee of a chiral primary amine via derivatization with 2-formylphenyl boronic acid and (S)-BINOL.
Figure 2: Range of racemic primary amines successfully derivatized to afford diastereoisomeric iminoboronate esters that display one or more sets of baseline-resolved diastereotopic resonances in their 1H NMR spectra.
Figure 3: Derivatization of (rac)-α-methylbenzylamine.
Figure 4: Determination of the enantiomeric exces of scalemic α-methylbenzylamine.

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Acknowledgements

We wish to thank the University of Bath, the EPSRC, the Leverhulme Trust and the Royal Society for financial support.

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  1. Department of Chemistry, University of Bath, Bath, BA2 7AY, UK

    Yolanda Pérez-Fuertes, Andrew M Kelly, John S Fossey, Magdalena E Powell, Steven D Bull & Tony D James

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  1. Yolanda Pérez-Fuertes
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Correspondence to Steven D Bull or Tony D James.

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Pérez-Fuertes, Y., Kelly, A., Fossey, J. et al. Simple protocols for NMR analysis of the enantiomeric purity of chiral primary amines. Nat Protoc 3, 210–214 (2008). https://doi.org/10.1038/nprot.2007.524

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