Abstract
A three-component chiral derivatization protocol for determining the enantiopurity of chiral diols by 1H NMR spectroscopic analysis is described here. The present approach involves the derivatization of 1,2- 1,3- and 1,4-diols with 2-formylphenylboronic acid and enantiopure α-methylbenzylamine. This method affords a mixture of diastereoisomeric iminoboronate esters whose ratio can be determined by integration of well-resolved diastereotopic resonances in their 1H NMR spectra, thus enabling the determination of the enantiopurity of the parent diol. The protocol as described takes less than 90 min to complete.
This is a preview of subscription content, access via your institution
Access options
Similar content being viewed by others
References
Kolb, H.C., VanNieuwenhze, M.S. & Sharpless, K.B. Catalytic asymmetric dihydroxylation. Chem. Rev. 94, 2483–2547 (1994).
Challenger, C.A. Chiral Intermediates. Wiley: London, 2001.
Hanessian, S. Total Synthesis of Natural Products: The Chiron Approach. Pergamon: London, 1983.
Parker, D. NMR determination of enantiomeric purity. Chem. Rev., 91, 1441–1457 (1991).
Dale, J.A. & Mosher, H.S. Nuclear magnetic resonance enantiomer regents. Configurational correlations via nuclear magnetic resonance chemical shifts of diastereomeric mandelate, O-methylmandelate, and alpha-methoxy-alpha-trifluoromethylphenylacetate (MTPA) esters. J. Am. Chem. Soc. 95, 512–519 (1973).
Manuel Seco, J., Martino, M., Quiñoá, E. & Riguera, R. Absolute configuration of 1,n-diols by NMR: the importance of the combined anisotropic effects in bis-arylmethoxyacetates. Org. Lett. 2, 3261–3264 (2000).
Freire, F., Manuel Seco, J., Quiñoá, E. & Riguera, R. Determining the absolute stereochemistry of secondary/secondary diols by 1H NMR: basis and applications. J. Org. Chem. 70, 3778–3790 (2005).
Freire, F., Manuel Seco, J. & Riguera, R. The assignment of the absolute configuration and the identification of the pro R and Pro S methylene protons in 1,2-diols by low temperature NMR of a single derivative. Org. Lett. 7, 4855–4858 (2005).
Kouda, K., Ooi, T. & Kusumi, T. Application of the modified Mosher's method to linear 1,3-diols. Tetrahedron Lett. 40, 3005–3008 (1999).
Trost, B.M., Belletire, J.L., Godleski, S., McDougal, P.G., Balkovec, J.M., Baldwin, J.J., Christy, M.E., Ponticello, G.S., Varga, S.L. & Springer, J.P. On the use of the O-methylmandelate ester for establishment of absolute-configuration of secondary alcohols. J. Org. Chem. 51, 2370–2374 (1986).
Brunel, J.M. & Faure, B. A new 31P NMR method for the enantiomeric excess determination of diols and secondary diamines with C2 symmetry. Tetrahedron Asymmetry 6, 2353–2356 (1995).
Garner, C.M., McWhorter, C. & Goerke, A.R. Methyldichlorophosphate: a chiral derivatizing agent for symmetrical diols. Tetrahedron Lett. 38, 7717–7720 (1997).
Fukui, H., Fukushi, Y. & Tahara, S. NMR determination of the absolute configuration of chiral 1,2- and 1,3-diols. Tetrahedron Lett. 44, 4063–4065 (2003).
Tokles, M. & Snyder, J.K. Camphanylboronic acid, a chiral derivatizing agent for optical purity determination of diols. Tetrahedron Lett. 29, 6063–6066 (1988).
Burgess, K. & Porte, A.M. Reagent for determining optical purities of diols via formation of diastereomeric arylboronate esters. Angew. Chem. Int. Ed. Engl. 33, 1182–1184 (1994).
Caselli, E., Danieli, C., Morandi, S., Bonfiglio, B., Forni, A. & Prati, F. (S)-(+)-N-Acetylphenylglycineboronic acid: a chiral derivatizing agent for ee determination of 1,2-diols. Org. Lett. 5, 4863–4866 (2003).
Resnick, S.M., Torok, D.S. & Gibson, D.T. Chemoenzymic synthesis of chiral boronates for the determination of the absolute configuration and enantiomeric excess of bacterial and synthetic cis-dienediols. J. Org. Chem. 60, 3546–3549 (1995).
Morandi, S., Caselli, E., Forni, A., Bucciarelli, M., Torre, G. & Prati, F. Enantiomeric excess of 1,2-diols by formation of cyclic boronates: an improved method. Tetrahedron Asymmetry 16, 2918–2926 (2005).
Pérez-Fuertes, Y., Kelly, A.M., Johnson, A.L., Arimori, S., Bull, S.D. & James, T.D. Simple protocol for NMR analysis of the enantiomeric purity of primary amines. Org. Lett. 8, 609–612 (2006).
Kelly, A.M., Pérez-Fuertes, Y., Arimori, S., Bull, S.D. & James, T.D. Simple protocol for NMR analysis of the enantiomeric purity of diols. Org. Lett. 8, 1971–1974 (2006).
Axe, P. et al. Enantiopure pseudo-C3-symmetric titanium alkoxide with propeller-like chirality. Org. Lett. 9, 223–226 (2007).
Taylor, P.J.M. & Bull, S.D. An improved synthesis of deuterated Schoöllkopf's bis-lactim ether and its use for the asymmetric synthesis of (R)-[α-2H]-phenylalanine methyl esters. Tetrahedron Asymmetry 17, 1170–1178 (2006).
James, T.D. Saccharide-selective boronic acid based photoinduced electron transfer (PET) fluorescent sensors. Top. Curr. Chem. 277, 107–152 (2007).
James, T.D. & Shinkai, S. Artificial receptors as chemosensors for carbohydrates. Top. Curr. Chem. 218, 159–200 (2002).
Acknowledgements
We wish to thank the University of Bath, the EPSRC, the Leverhulme Trust, and the Royal Society for financial support.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Kelly, A., Pérez-Fuertes, Y., Fossey, J. et al. Simple protocols for NMR analysis of the enantiomeric purity of chiral diols. Nat Protoc 3, 215–219 (2008). https://doi.org/10.1038/nprot.2007.523
Published:
Issue Date:
DOI: https://doi.org/10.1038/nprot.2007.523
This article is cited by
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
