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Asymmetric additions to dienes catalysed by a dithiophosphoric acid

Nature volume 470, pages 245–249 (2011)Cite this article

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Abstract

Chiral Brønsted acids (proton donors) have been shown to facilitate a broad range of asymmetric chemical transformations under catalytic conditions without requiring additional toxic or expensive metals1,2,3,4,5,6,7,8. Although the catalysts developed thus far are remarkably effective at activating polarized functional groups, it is not clear whether organic Brønsted acids can be used to catalyse highly enantioselective transformations of unactivated carbon–carbon multiple bonds. This deficiency persists despite the fact that racemic acid-catalysed ‘Markovnikov’ additions to alkenes are well known chemical transformations. Here we show that chiral dithiophosphoric acids can catalyse the intramolecular hydroamination and hydroarylation of dienes and allenes to generate heterocyclic products in exceptional yield and enantiomeric excess. We present a mechanistic hypothesis that involves the addition of the acid catalyst to the diene, followed by nucleophilic displacement of the resulting dithiophosphate intermediate; we also report mass spectroscopic and deuterium labelling studies in support of the proposed mechanism. The catalysts and concepts revealed in this study should prove applicable to other asymmetric functionalizations of unsaturated systems.

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Figure 1: A possible solution to the mechanistic challenge of asymmetric acid-catalysed additions to alkenes.
Figure 2: Experiments to elucidate the reaction mechanism and application to indole nucleophiles.

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References

  1. 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 

  2. 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 

  3. Terada, M. Binaphthol-derived phosphoric acid as a versatile catalyst for enantioselective carbon–carbon bond forming reactions. Chem. Commun. 4097–4112 (2008)

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

    Article  CAS  Google Scholar 

  5. 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 

  6. Cheon, C. H. & Yamamoto, H. A Brønsted acid catalyst for the enantioselective protonation reaction. J. Am. Chem. Soc. 130, 9246–9247 (2008)

    Article  CAS  Google Scholar 

  7. Hatano, M., Maki, T., Moriyama, K., Arinobe, M. & Ishihara, K. Pyridinium 1,1′-binaphthyl-2,2′-disulfonates as highly effective chiral Brønsted acid−base combined salt catalysts for enantioselective Mannich-type reaction. J. Am. Chem. Soc. 130, 16858–16860 (2008)

    Article  CAS  Google Scholar 

  8. García-García, P., Lay, F., García-García, P., Rabalakos, C. & List, B. A powerful chiral counteranion motif for asymmetric catalysis. Angew. Chem. Int. Edn 48, 4363–4366 (2009)

    Article  Google Scholar 

  9. Aillaud, I., Collin, J., Hannedouche, J. & Schulz, E. Asymmetric hydroamination of non-activated carbon–carbon multiple bonds. Dalton Trans. 5105–5118 (2007)

  10. Hultzsch, K. C. Transition metal-catalyzed asymmetric hydroamination of alkenes (AHA). Adv. Synth. Catal. 347, 367–391 (2005)

    Article  CAS  Google Scholar 

  11. Hultzsch, K. C. Catalytic asymmetric hydroamination of non-activated olefins. Org. Biomol. Chem. 3, 1819–1824 (2005)

    Article  CAS  Google Scholar 

  12. Roesky, P. W. & Müller, T. E. Enantioselective catalytic hydroamination of alkenes. Angew. Chem. Int. Edn 42, 2708–2710 (2003)

    Article  CAS  Google Scholar 

  13. Schlummer, B. & Hartwig, J. F. Brønsted acid-catalyzed intramolecular hydroamination of protected alkenylamines. Synthesis of pyrrolidines and piperidines. Org. Lett. 4, 1471–1474 (2002)

    Article  CAS  Google Scholar 

  14. Rosenfeld, D. C., Shekhar, S., Takemiya, A., Utsunomiya, M. & Hartwig, J. F. Hydroamination and hydroalkoxylation catalyzed by triflic acid. Parallels to reactions initiated with metal triflates. Org. Lett. 8, 4179–4182 (2006)

    Article  CAS  Google Scholar 

  15. Li, Z. et al. Brønsted acid catalyzed addition of phenols, carboxylic acids, and tosylamides to simple olefins. Org. Lett. 8, 4175–4178 (2006)

    Article  CAS  Google Scholar 

  16. Ackermann, L. & Althammer, A. Phosphoric acid diesters as efficient catalysts for hydroaminations of nonactivated alkenes and an application to asymmetric hydroamination. Synlett 995–998 (2008)

  17. MacMillan, D. W. C. The advent and development of organocatalysis. Nature 455, 304–308 (2008)

    Article  ADS  CAS  Google Scholar 

  18. Norman, G. R., LeSuer, W. M. & Mastin, T. W. Chemistry of the aliphatic esters of thiophosphoric acids. II. O,O,S-trialkyl thionophosphates by the addition of O,O-dialkyl thiolthionophosphoric acids to olefins. J. Am. Chem. Soc. 74, 161–163 (1952)

    Article  Google Scholar 

  19. Kabachnik, M. I., Mastrukova, T. A., Shipov, A. E. & Melentyeva, T. A. The application of the Hammett equation to the theory of tautomeric equilibrium: thione-thiol equilibrium, acidity, and structure of phosphorous thioacids. Tetrahedron 9, 10–28 (1960)

    Article  CAS  Google Scholar 

  20. Mastryukova, T. A., Spivak, L. L., Grigoreva, A. A., Urzhuntseva, E. K. & Kabachnik, M. I. Ionization constants of phosphorus dithio acids in absolute ethanol. J. Gen. Chem. USSR (Engl. Transl.) 41, 1938–1941 (1971)

    CAS  Google Scholar 

  21. Leavitt, C. M. et al. Investigations of acidity and nucleophilicity of diphenyldithiophosphinate ligands using theory and gas-phase dissociation reactions. Inorg. Chem. 47, 3056–3064 (2008)

    Article  CAS  Google Scholar 

  22. Mueller, W. H. & Oswald, A. A. Organic sulfur compounds. XV. Cationic addition of O,O′-diethylthiophosphoric acid to olefins. J. Org. Chem. 31, 1894–1898 (1966)

    Article  CAS  Google Scholar 

  23. Pousse, G. et al. Synthesis of BINOL derived phosphorodithioic acids as new chiral Brønsted acids and an improved synthesis of 3,3′-disubstituted H8-BINOL derivatives. Tetrahedron 65, 10617–10622 (2009)

    Article  CAS  Google Scholar 

  24. Cheng, X. C., Wang, Q., Fang, H., Tang, W. & Xu, W. F. Synthesis of new sulfonyl pyrrolidine derivatives as matrix metalloproteinase inhibitors. Bioorg. Med. Chem. 16, 7932–7938 (2008)

    Article  CAS  Google Scholar 

  25. Mutel, V. & Wichmann, J. Sulfonyl-pyrrolidine derivatives useful for the treatment of neurological disorders. European patent 1,299. 383 (2005)

  26. Obushak, N. D., Vovk, M. V., Vengrzhanovskii, V. A., Mel'nik, Y. I. & Ganushchak, N. I. Regioselective addition of O,O-diethyl dithiophosphate to 1-aryl-1,3-butadienes. J. Gen. Chem. USSR (Engl. Transl.) 57, 1078–1080 (1987)

    CAS  Google Scholar 

  27. Mebah, J. M. N., Mieloszynski, J. L. & Paquer, D. Reactivity of O,O-diethyldithiophosphoric acid toward different ethylenic systems. Phosphorus Sulfur Silicon Relat. Elem. 73, 49–56 (1992)

    Article  CAS  Google Scholar 

  28. Houk, K. N., Paddon-Row, M. N. & Rondan, N. G. The origin of syn stereoselectivity in the SN2′ reaction. J. Mol. Struct. 103, 197–208 (1983)

    Article  Google Scholar 

  29. Borrmann, T. & Stohrer, W. What governs the stereochemistry of the SN2′ reaction? Liebigs Ann. 1996, 1593–1597 (1996)

    Article  Google Scholar 

  30. Liu, C. & Widenhoefer, R. A. Gold(I)-catalyzed intramolecular enantioselective hydroarylation of allenes with indoles. Org. Lett. 9, 1935–1938 (2007)

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to D. Benitez and E. Tkatchouk (Goddard Group, California Institute of Technology) for performing DFT calculations, to U. Anderson and T. Iavarone of the QB3/Chemistry Mass Spectrometry Facility, and to A. DiPasquale of the X-ray Crystallography Facility. We acknowledge funding from the Director, Office of Science of the US Department of Energy (contract no. DE-AC02-05CH11231) and from NIHGMS (R01 GM074774). V.R. is grateful for a Natural Sciences and Engineering Research Council of Canada (NSERC) postdoctoral fellowship. G.L.H. is grateful for a Bristol-Myers/Squibb graduate fellowship.

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Author notes

  1. Nathan D. Shapiro and Vivek Rauniyar: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, University of California, Berkeley, 94720, California, USA

    Nathan D. Shapiro, Vivek Rauniyar, Gregory L. Hamilton, Jeffrey Wu & F. Dean Toste

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Contributions

N.D.S. initiated the hydroamination study. V.R. optimized the catalysts and initiated the hydroarylation study. N.D.S., V.R., G.L.H. and J.W. performed the experiments. N.D.S., G.L.H. and F.D.T. developed the mechanistic concepts. G.L.H. and N.D.S. wrote the manuscript with input from all authors.

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Correspondence to F. Dean Toste.

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The authors declare no competing financial interests.

Additional information

X-ray crystallographic data have been deposited in the Cambridge Crystallographic Data Centre database (http://www.ccdc.cam.ac.uk/) under code CCDC 800545.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-11 with legends, Supplementary Table 1, additional references and Supplementary data (Copies of NMR and HPLC spectra). (PDF 5334 kb)

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Shapiro, N., Rauniyar, V., Hamilton, G. et al. Asymmetric additions to dienes catalysed by a dithiophosphoric acid. Nature 470, 245–249 (2011). https://doi.org/10.1038/nature09723

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