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Asymmetric spiroacetalization catalysed by confined Brønsted acids

Nature volume 483, pages 315–319 (2012)Cite this article

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Abstract

Acetals are molecular substructures that contain two oxygen–carbon single bonds at the same carbon atom, and are used in cells to construct carbohydrates and numerous other molecules. A distinctive subgroup are spiroacetals, acetals joining two rings, which occur in a broad range of biologically active compounds, including small insect pheromones and more complex macrocycles1,2. Despite numerous methods for the catalytic asymmetric formation of other commonly occurring stereocentres, there are few approaches that exclusively target the chiral acetal centre and none for spiroacetals3,4. Here we report the design and synthesis of confined Brønsted acids based on a C2-symmetric imidodiphosphoric acid motif, enabling a catalytic enantioselective spiroacetalization reaction. These rationally constructed Brønsted acids possess an extremely sterically demanding chiral microenvironment, with a single catalytically relevant and geometrically constrained bifunctional active site. Our catalyst design is expected to be of broad utility in catalytic asymmetric reactions involving small and structurally or functionally unbiased substrates.

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Figure 1: Towards catalytic asymmetric synthesis of olean.
Figure 2: Development of C 2 -symmetric imidodiphosphoric acids.
Figure 3: Comparison of crystal structures of anions of 6a (6 with R = 2,4,6-Et 3 C 6 H 2 ) and TRIP.

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Data deposits

X-ray crystallographic data have been deposited in the Cambridge Crystallographic Data Centre database (http://www.ccdc.cam.ac.uk/) under accession code CCDC 864762.

References

  1. Perron, F. & Albizati, K. F. Chemistry of spiroketals. Chem. Rev. 89, 1617–1661 (1989)

    Article  CAS  Google Scholar 

  2. Aho, J. E., Pihko, P. M. & Rissa, T. K. Nonanomeric spiroketals in natural products: structures, sources, and synthetic strategies. Chem. Rev. 105, 4406–4440 (2005)

    Article  CAS  Google Scholar 

  3. Čorić, I., Vellalath, S. & List, B. Catalytic asymmetric transacetalization. J. Am. Chem. Soc. 132, 8536–8537 (2010)

    Article  Google Scholar 

  4. Nagano, H. & Katsuki, T. Stereocontrolled OH protection: asymmetric tetrahydrofuranylation. Chem. Lett. 31, 782–783 (2002)

    Article  Google Scholar 

  5. Zinzalla, G., Milroy, L.-G. & Ley, S. V. Chemical variation of natural product-like scaffolds: design and synthesis of spiroketal derivatives. Org. Biomol. Chem. 4, 1977–2002 (2006)

    Article  CAS  Google Scholar 

  6. Brasholz, M., Sörgel, S., Azap, C. & Reißig, H.-U. Rubromycins: structurally intriguing, biologically valuable, synthetically challenging antitumour antibiotics. Eur. J. Org. Chem. 3801–3814 (2007)

  7. Haniotakis, G., Francke, W., Mori, K., Redlich, H. & Schurig, V. Sex-specific activity of (R)-(−)- and (S)- (+)-1,7-dioxaspiro[5.5]undecane, the major pheromone of Dacus oleae. J. Chem. Ecol. 12, 1559–1568 (1986)

    Article  CAS  Google Scholar 

  8. Redlich, H. & Francke, W. Synthesis of enantiomerically pure 1,7-dioxaspiro[5.5]undecanes, pheromone components of the olive fly (Dacus oleae). Angew. Chem. Int. Ed. 23, 519–520 (1984)

    Article  Google Scholar 

  9. Takahashi, S. et al. Reveromycin A biosynthesis uses RevG and RevJ for stereospecific spiroacetal formation. Nature Chem. Biol. 7, 461–468 (2011)

    Article  CAS  Google Scholar 

  10. Takaoka, L. R., Buckmelter, A. J., LaCruz, T. E. & Rychnovsky, S. D. Rational synthesis of contra-thermodynamic spiroacetals by reductive cyclizations. J. Am. Chem. Soc. 127, 528–529 (2005)

    Article  CAS  Google Scholar 

  11. Moilanen, S. B., Potuzak, J. S. & Tan, D. S. Stereocontrolled synthesis of spiroketals via Ti(Oi-Pr)4-mediated kinetic spirocyclization of glycal epoxides with retention of configuration. J. Am. Chem. Soc. 128, 1792–1793 (2006)

    Article  CAS  Google Scholar 

  12. Audrain, H., Thorhauge, J., Hazell, R. G. & Jørgensen, K. A. A novel catalytic and highly enantioselective approach for the synthesis of optically active carbohydrate derivatives. J. Org. Chem. 65, 4487–4497 (2000)

    Article  CAS  Google Scholar 

  13. Akiyama, T., Itoh, J., Yokota, K. & Fuchibe, K. Enantioselective Mannich-type reaction catalyzed by a chiral Brønsted acid. Angew. Chem. Int. Edn 43, 1566–1568 (2004)

    Article  CAS  Google Scholar 

  14. Uraguchi, D. & Terada, M. Chiral Brønsted acid-catalyzed direct Mannich reactions via electrophilic activation. J. Am. Chem. Soc. 126, 5356–5357 (2004)

    Article  CAS  Google Scholar 

  15. Akiyama, T. Stronger Brønsted acids. Chem. Rev. 107, 5744–5758 (2007)

    Article  CAS  Google Scholar 

  16. Nakashima, D. & Yamamoto, H. Design of chiral N-triflyl phosphoramide as a strong chiral Brønsted acid and its application to asymmetric Diels-Alder reaction. J. Am. Chem. Soc. 128, 9626–9627 (2006)

    Article  CAS  Google Scholar 

  17. Doyle, A. G. & Jacobsen, E. N. Small-molecule H-bond donors in asymmetric catalysis. Chem. Rev. 107, 5713–5743 (2007)

    Article  CAS  Google Scholar 

  18. Huang, Y., Unni, K. A., Thadani, A. N. & Rawal, V. H. Single enantiomers from a chiral-alcohol catalyst. Nature 424, 146 (2003)

    Article  CAS  ADS  Google Scholar 

  19. Zhang, Q.-W. et al. Brønsted acid catalyzed enantioselective semipinacol rearrangement for the synthesis of chiral spiroethers. Angew. Chem. Int. Edn 48, 8572–8574 (2009)

    Article  CAS  Google Scholar 

  20. Shenoy, S. R., Crisóstomo, F. R. P., Iwasawa, T. & Rebek, J., Jr Organocatalysis in a synthetic receptor with an inwardly directed carboxylic acid. J. Am. Chem. Soc. 130, 5658–5659 (2008)

    Article  CAS  Google Scholar 

  21. Hastings, C. J., Pluth, M. D., Bergman, R. G. & Raymond, K. N. Enzymelike catalysis of the Nazarov cyclization by supramolecular encapsulation. J. Am. Chem. Soc. 132, 6938–6940 (2010)

    Article  CAS  Google Scholar 

  22. Vellalath, S., Čorić, I. & List, B. N-Phosphinyl phosphoramide—a chiral Brønsted acid motif for the direct asymmetric N,O-acetalization of aldehydes. Angew. Chem. Int. Edn 49, 9749–9752 (2010)

    Article  CAS  Google Scholar 

  23. Xu, F. et al. SPINOL-Derived phosphoric acids: synthesis and application in enantioselective Friedel-Crafts reaction of indoles with imines. J. Org. Chem. 75, 8677–8680 (2010)

    Article  CAS  Google Scholar 

  24. Čorić, I., Müller, S. & List, B. Kinetic resolution of homoaldols via catalytic asymmetric transacetalization. J. Am. Chem. Soc. 132, 17370–17373 (2010)

    Article  Google Scholar 

  25. Klussmann, M. et al. Synthesis of TRIP and analysis of phosphate salt impurities. Synlett 2189–2192 (2010)

    Article  Google Scholar 

  26. Wall, M. E., Eddy, C. R. & Serota, S. Steroidal sapogenins. XIX. Stereochemistry of sapogenins and cholesterol at carbon 20. J. Am. Chem. Soc. 76, 2849–2850 (1954)

    Article  CAS  Google Scholar 

  27. Shapiro, N. D., Rauniyar, V., Hamilton, G. L., Wu, J. & Toste, F. D. Asymmetric additions to dienes catalysed by a dithiophosphoric acid. Nature 470, 245–249 (2011)

    Article  CAS  ADS  Google Scholar 

  28. Mayer, S. & List, B. Asymmetric counteranion-directed catalysis. Angew. Chem. Int. Edn 45, 4193–4195 (2006)

    Article  CAS  Google Scholar 

  29. Hamilton, G. L., Kang, E. J., Mba, M. & Toste, F. D. A powerful chiral counterion strategy for asymmetric transition metal catalysis. Science 317, 496–499 (2007)

    Article  CAS  ADS  Google Scholar 

  30. Mukherjee, S. & List, B. Chiral counteranions in asymmetric transition-metal catalysis: highly enantioselective Pd/Brønsted acid-catalyzed direct α-allylation of aldehydes. J. Am. Chem. Soc. 129, 11336–11337 (2007)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. Dreier and R. Goddard for crystal structure analysis of catalyst 6a. S. Vellalath and S. Müller are acknowledged for donating several previously described catalysts, and N. Wippich and S. Dehn for technical assistance. We gratefully acknowledge support from the Max Planck Sociey and the European Research Council.

Author information

Authors and Affiliations

  1. Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany,

    Ilija Čorić & Benjamin List

Authors
  1. Ilija Čorić
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  2. Benjamin List
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Contributions

I.Č. and B.L. jointly designed and developed C2-symmetric imidodiphosphoric acids, developed the spiroacetalization reaction, and wrote the manuscript. I.Č. conducted the laboratory experiments. B.L. initiated and oversaw the project.

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Correspondence to Benjamin List.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-4, Supplementary Tables 1-6, Supplementary Methods, Supplementary References and Supplementary Data. The figures in the Supplementary Data show synthetic routes used and crystal structure of the catalyst 6a with probability ellipsoids. (PDF 4230 kb)

Supplementary Data

This file contains the crystallographic information for catalyst 6a. (ZIP 17 kb)

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Čorić, I., List, B. Asymmetric spiroacetalization catalysed by confined Brønsted acids. Nature 483, 315–319 (2012). https://doi.org/10.1038/nature10932

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