Advertisement

Journal of Flow Chemistry

, Volume 3, Issue 2, pp 29–33 | Cite as

Microreactor-Mediated Organocatalysis: Towards the Development of Sustainable Domino Reactions

  • Laura Carroccia
  • Biagia Musio
  • Leonardo Degennaro
  • Giuseppe Romanazzi
  • Renzo Luisi
Communication

Abstract

Microreactor-mediated organocatalysed Michael reactions have been developed. By using a soluble proline-derived catalyst, Michael-type reactions, leading to γ-nitroketones, have been optimized in homogeneous and continuous-flow conditions. As proof of principle, an integrated microfluidic system able to perform domino processes useful in the preparation of bicyclo[4.4.0]decanes with six contiguous stereogenic centres has been set up.

Keywords

microreactor technology organocatalysis Michael addition stereoselective synthesis 

Supplementary material

41981_2013_3020029_MOESM1_ESM.pdf (6 mb)
Supplementary material, approximately 6337 KB.

Notes and References

  1. 1.(a)
    Berkessel, A.; Gröger, H. Asymmetrie Organocatalysìs; Wiley-VCH: Weinheim, 2005CrossRefGoogle Scholar
  2. (b).
    Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719CrossRefGoogle Scholar
  3. (c).
    Marigo, M.; Jørgensen, K. A. Chem. Commun. 2006, 2001Google Scholar
  4. (d).
    List, B. Chem. Commun. 2006, 819Google Scholar
  5. (e).
    Lelais, G.; MacMillan, D. W. C. Aldrichimica Acta 2006, 39, 79Google Scholar
  6. (f).
    List, B. Chem. Rev. 2007, 107, 5413CrossRefGoogle Scholar
  7. (g).
    de Figueiredo, R. M.; Christmann, M. Eur. J. Org. Chem. 2007, 2575Google Scholar
  8. (h).
    Dalko, R I. Enantioselective Organocatalysìs. Reactions and Expérimental Procédures; Wiley-VCH: Weinheim, 2007Google Scholar
  9. (i).
    Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606CrossRefGoogle Scholar
  10. (j).
    Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G. Angew. Chem. Int. Ed. 2008, 47, 6138.CrossRefGoogle Scholar
  11. 2.(a)
    Geyer, K.; Codée, J. D. C.; Seeberger, R. H. Chem. Eur. J. 2006, 12, 8434CrossRefGoogle Scholar
  12. (b).
    deMello, A. J. Nature 2006, 442, 394CrossRefGoogle Scholar
  13. (c).
    Mason, B. P.; Priée, K. E.; Steinbacher, J. L.; Bogdan, A. R.; McQuade, D. T. Chem. Rev. 2007, 107, 2300CrossRefGoogle Scholar
  14. (d).
    Yoshida, J.-I.; Nagaki, A.; Yamada, T. Chem. Eur. J. 2008, 14, 7450CrossRefGoogle Scholar
  15. (e).
    Yoshida, J.-I.; Kim, H.; Nagaki, A. Chem Sus Chem 2011, 4, 331CrossRefGoogle Scholar
  16. (f).
    Hartman, R. I.; McMullen, J. P.; Jensen, K. F. Angew. Chem. Int. Ed. 2011, 50, 7502.CrossRefGoogle Scholar
  17. 3.(a)
    Wegner, J.; Ceylan, S.; Kirsching, A. Chem. Commun. 2011, 47, 4583CrossRefGoogle Scholar
  18. (b).
    Wiles, C.; Watts, P. In Micro Reaction Technology in Organic Synthesis; CRC Press, Taylor & Francis Group: Boca Raton, FL, 2011Google Scholar
  19. (c).
    Wirth, T. In Microreactors in Organic Synthesis and Catalysis; Wirth, T., Ed.; Wiley-VCH Verlag GmbH & Co.: Weinheim, 2008.Google Scholar
  20. 4.
    Mak, X. Y.; Laurino, P.; Seeberger, P. H. Beilstein J. Org. Chem. 2009, 5, 19.CrossRefGoogle Scholar
  21. 5.
    For examples of heterogeneous organocatalyzed continuous flow reactions see:(a) Ayats, C.; Henseler, A. H.; Pericàs, M. A. ChemSusChem 2012, 5, 320CrossRefGoogle Scholar
  22. (b).
    Cambeiro, X. C.; Martin-Rapün, R.; Miranda, P. O.; Sayalero, S.; Alza, E.; Lianes, P.; Pericàs, M. A. Beilstein J. Org. Chem. 2011, 7, 1486CrossRefGoogle Scholar
  23. (c).
    Otvos, S. B.; Mandity, I. M.; Fulop, F. ChemSusChem 2012, 5, 266CrossRefGoogle Scholar
  24. (d).
    Bortolini, O.; Caciolli, L.; Cavazzini, A.; Costa, V.; Greco, R.; Massi, A.; Pasti, L. Green. Chem. 2012, 14, 992CrossRefGoogle Scholar
  25. (e).
    Alza, E.; Rodriguez-Escrich, C.; Sayalero, S.; Basterò, A.; Pericàs, M.A. Chem. Eur. J. 2009, 15, 10167CrossRefGoogle Scholar
  26. (f).
    Xinyuan, F.; Sayalero, S.; Pericàs, M. A. Adv. Synth. Catal. 2012, 354, 2971CrossRefGoogle Scholar
  27. (g).
    Arakawa, Y.; Wennemers, H. ChemSusChem 2013, 6, 242.CrossRefGoogle Scholar
  28. 6.(a)
    Yang, J.; Qi, L.; Qiao, J.; Chen, Y; Ma, H. Chin. J. Chem. 2011, 29, 2385CrossRefGoogle Scholar
  29. (b).
    Odedra, A.; Seeberger, P. H. Angew. Chem. Int. Ed. 2009, 48, 2699CrossRefGoogle Scholar
  30. (c).
    Rueping, M.; Bootwicha, T.; Sugiono, E. Beilstein J. Org. Chem. 2012, 8, 300CrossRefGoogle Scholar
  31. (d).
    Shen, B.; Jamison, T. F. Org. Lett, 2012, 14, 3348CrossRefGoogle Scholar
  32. (e).
    Fritzsche, S.; Ohla, S.; Glaser, P.; Giera, D. S.; Sickert, M.; Schneider, C.; Beider, D. Angew. Chem. Int. Ed. 2011, 50, 9467.CrossRefGoogle Scholar
  33. 7.
    Opalka, S. M.; Longstreet, A. R.; McQuade, D. T. Beilstein J. Org. Chem. 2011, 7, 1671.CrossRefGoogle Scholar
  34. 8.
    For selected reviews on organocatalytic domino reactions, see: (a) Enders, D.; Grondai, C.; Hüttl, M. R. M. Angew. Chem. Int. Ed. 2007, 46, 1570CrossRefGoogle Scholar
  35. (b).
    Yu, X.; Wang, W. Org. Biomol. Chem. 2008, 6, 2037CrossRefGoogle Scholar
  36. (c).
    Alba, A. N.; Companyo, X.; Viciano, M.; Rios, R. Curr. Org. Chem. 2009, 13, 1432CrossRefGoogle Scholar
  37. (d).
    Grossmann, A.; Enders, D. Angew. Chem. Int. Ed. 2012, 51, 314CrossRefGoogle Scholar
  38. (e).
    Pellissier, H. Adv. Synth. Catal. 2012, 354, 237CrossRefGoogle Scholar
  39. (f).
    Wu, L.-Y.; Bencivenni, G.; Mancinelli, M.; Mazzanti, A.; Battoli, G.; Melchiorre, P. Angew. Chem. Int. Ed. 2009, 48, 7196.CrossRefGoogle Scholar
  40. 9.(a)
    Enders, D.; Urbanietz, G.; Cassens-Sasse, E.; Keeß, S.; Raabe, G. Adv. Synth. Catal. 2012, 354, 1481CrossRefGoogle Scholar
  41. (b).
    Zeng, X.; Ni, Q.; Raabe, G.; Enders, D. Angew. Chem. Int. Ed. 2013, 52, 2977CrossRefGoogle Scholar
  42. (c).
    Anwar, S.; Chang, H.-J.; Chen, K. Org. Lett. 2011, 13, 2200.CrossRefGoogle Scholar
  43. 10.
    Alza, E.; Sayalero, S.; Cambeiro, X. C.; Martín-Rapún, R.; Miranda, P. O.; Pericàs, M. A. Synlett 2011, 464.Google Scholar
  44. 11.(a)
    List, B.; Pojarliev, P.; Martin, H. J. Org. Lett. 2001, 3, 2423CrossRefGoogle Scholar
  45. (b).
    Enders, D.; Seki, A. Synlett 1, 26.Google Scholar
  46. 12.(a)
    Franzén, J.; Mango, M.; Fielenbach, D.; Wabnitz, T. C.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 18296CrossRefGoogle Scholar
  47. (b).
    Marigo, M.; Wabnitz, T. C.; Fielenbach, D.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2005, 44, 794.CrossRefGoogle Scholar
  48. 13.
    Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem. Int. Ed. 2005, 44, 4212.CrossRefGoogle Scholar
  49. 14.
    Tan, B.; Zeng, X.; Lu, Y.; Chua, P. J.; Zhong, G. Org. Lett. 2009, 11, 1927.CrossRefGoogle Scholar
  50. 15.
    In order to find homogenous conditions suitable for the chip microreactor, several catalysts and solvents were tested in macrobatch conditions (see Figure 1). Catalyst la in DMSO was found to be the best choice for this investigation.Google Scholar
  51. 16.(a)
    Jiao, P.; Kawasaki, M.; Yamamoto, H. Angew. Chem. Int. Ed. 2009, 48, 3333CrossRefGoogle Scholar
  52. (b).
    Torii, H.; Nakadai, M.; Ishihara, K.; Saito S.; Yamamoto, H. Angew. Chem. Int. Ed. 2004, 43, 1983CrossRefGoogle Scholar
  53. (c).
    Longbottom, D. A.; Frankevicivus, V.; Kumarn, S.; Oelke, A. J.; Wascholowski, V.; Ley, S. V. Aldrichimica Acta 2008, 41, 3Google Scholar
  54. (d).
    Cobb, A. J. A.; Shaw, D. M.; Ley, S. V. Synlett 2004, 558.Google Scholar
  55. 17.
    An automated Asia® system was employed for the experiments. More détails at www.syrris.com.
  56. 18.
    During this optimization study, it was mandatory to keep homogeneous conditions, avoiding any clogging, in ali the reaction conditions adopted.Google Scholar
  57. 19.(a)
    Cobb, A. J. A.; Shaw, D. M.; Longbottom, D. A.; Gold, J. B.; Ley, S. V. Org. Biomol. Chem. 2005, 3, 84.CrossRefGoogle Scholar
  58. (b).
    Cobb, A. J. A.; Longbottom, D. A.; Shaw, D. M.; Gold, J. B.; Ley, S. V. Chem. Commun. 2004, 1808.Google Scholar
  59. 20.
    Almost the same enantioselectivity observed in macrobatch mode was reproduced for this type of reaction/catalyst pair in microflow conditions.Google Scholar
  60. 21.
    It is worth mentioning that the use of the catalyst la is mandatory in order to observe conversion of the reactants and diastereoselectivity. No reaction was observed in the absence of the catalyst under the same continuous flow conditions.Google Scholar

Copyright information

© Akadémiai Kiadó 2013

Authors and Affiliations

  • Laura Carroccia
    • 1
  • Biagia Musio
    • 1
  • Leonardo Degennaro
    • 1
  • Giuseppe Romanazzi
    • 2
  • Renzo Luisi
    • 1
  1. 1.Department of PharmacyUniversity of Bari “A. Moro,”BariItaly
  2. 2.DICATEChPolytechnic of BariBariItaly

Personalised recommendations