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[3,3] Paracyclophanes as Planar Chiral Scaffolds for the Synthesis of New Phosphoric Acids.

EWPC 10 – Regensburg – 19/03/13. [3,3] Paracyclophanes as Planar Chiral Scaffolds for the Synthesis of New Phosphoric Acids. Jérémie Stemper. Dr. J.F. Betzer Dr. A. Voituriez Dr. A. Marinetti. EWPC 10 – Regensburg – 19/03/13. Phosphoric acids as organocatalysts.

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[3,3] Paracyclophanes as Planar Chiral Scaffolds for the Synthesis of New Phosphoric Acids.

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  1. EWPC 10 – Regensburg – 19/03/13 [3,3]Paracyclophanes as Planar Chiral Scaffolds for the Synthesis of New Phosphoric Acids. Jérémie Stemper Dr. J.F. Betzer Dr. A. Voituriez Dr. A. Marinetti

  2. EWPC 10 – Regensburg – 19/03/13 Phosphoricacids as organocatalysts Brønsted basic site Bifunctionalcatalyst Brønstedacidic site Steric and electroniceffects * Terada, M. Bull. Chem. Soc. Jpn. 2010,Vol. 83, 101-119

  3. EWPC 10 – Regensburg – 19/03/13 Phosphoricacids as organocatalysts First examples of catalysiswithchiral phosphoricacids by Teradaand Akiyamain 2004 : Yields up to 99% e.e. up to 95% Yields up to 99% e.e. up to 96% Syn/anti ratio up to 100:0 Terada, M. et al., J. Am. Chem. Soc.2004, 17, 5356 Akiyama, T. et al., Angew. Chem. Int. Ed. 2004, 12, 1566

  4. EWPC 10 – Regensburg – 19/03/13 Phosphoricacids as organocatalysts A wide range of syntheticalyusefull transformations is possible underphosphoricacidscatalysis : List, B. et al.,Top. Curr. Chem.2010, 395 Terada, M. et al., Synthesis2010, 12, 1929

  5. EWPC 10 – Regensburg – 19/03/13 Most representativechiral phosphoricacidsfromthelitterature: List, Wang, 2010 Terada, Akiyama, 2004 Akiyama, Charette, 2005 Central chirality Axial chirality Terada, M. et al., J. Am. Chem. Soc.2004, 17, 5356 Akiyama, T. et al., Angew. Chem. Int. Ed. 2004, 12, 1566 List, B. et al., J. Am. Chem. Soc. 2010, 132, 17370 Wang, Y. et al., J. Org. Chem. 2010, 75, 8677 Akiyama, T. et al., Adv. Syn. Catal. 2005, 347, 1523 Charette, A. B. et al., Adv. Syn. Catal. 2006, 348, 2363

  6. EWPC 10 – Regensburg – 19/03/13 Most representativechiral phosphoricacidsfromthelitterature: List, Wang, 2010 Terada, Akiyama, 2004 Akiyama, Charette, 2005 Central chirality Axial chirality 1 example by Enders in 2012 Planarchirality ? Enders, D. D. et al.,Chirality2012 , 215

  7. EWPC 10 – Regensburg – 19/03/13 Target structure

  8. EWPC 10 – Regensburg – 19/03/13 Target structure Planarchirality

  9. EWPC 10 – Regensburg – 19/03/13 Target structure Planarchirality Enantioselectivity

  10. EWPC 10 – Regensburg – 19/03/13 Target structure Tunable motif Planarchirality Enantioselectivity

  11. EWPC 10 – Regensburg – 19/03/13 DFT calculations ΔG kj.mol-1 BINOL Dr. Gilles Frison, Ecole polytechnique

  12. EWPC 10 – Regensburg – 19/03/13 DFT calculations ΔG kj.mol-1 BINOL Dr. Gilles Frison, Ecole polytechnique

  13. EWPC 10 – Regensburg – 19/03/13 Syntheticstrategy Functionalizedferrocene Macrocyclisation Cross-coupling Ferrocene-Biaryl Biaryl

  14. EWPC 10 – Regensburg – 19/03/13 Syntheticstrategy

  15. EWPC 10 – Regensburg – 19/03/13 Syntheticstrategy

  16. EWPC 10 – Regensburg – 19/03/13 Syntheticstrategy Heptane : THF : NEt3 : TFA 40:60:0.3:0.5 1mL/min (±) Resolution by chiral HPLC (+) 6.45 min (-) 14.33 min [α]D= + 931 (c=1.0, CHCl3) Column : Chiralpak ID Stationary phase :

  17. EWPC 10 – Regensburg – 19/03/13 X-Ray analysis : P P Non C2 symmetric Dr. Pascal Retailleau

  18. EWPC 10 – Regensburg – 19/03/13 • Ferroceneis asuitabletethering unit But • In order to synthetise a wholeseries of phosphoricacids :

  19. EWPC 10 – Regensburg – 19/03/13 • Ferroceneis a suitabletethering unit But • In order to synthesizea wholeseries of phosphoricacids : Introduction of arylsubstituentsat alaterstepof the reactionsequence Easierresolution of the enantiomers

  20. EWPC 10 – Regensburg – 19/03/13 New Syntheticpathway 1) Introduction of diversity Key intermediateallowingeasy variation of substituents

  21. EWPC 10 – Regensburg – 19/03/13 New Synthetic pathway 2) Synthesis of an epimeric mixture

  22. EWPC 10 – Regensburg – 19/03/13 New Syntheticpathway 3) Resolution SiO2

  23. EWPC 10 – Regensburg – 19/03/13 Catalysis : 1) Preliminaryevaluation Rueping, M. et al.,Angew. Chem. Int. Ed. 2006, 45, 3683

  24. EWPC 10 – Regensburg – 19/03/13 Catalysis : 1) Preliminaryevaluation yield = 98% ee = 31% Good catalyticactivity

  25. EWPC 10 – Regensburg – 19/03/13 Catalysis : 2) Optimisation Hantzsch ester, R = Et Ph

  26. EWPC 10 – Regensburg – 19/03/13 Catalysis : 2) Optimisation Hantzsch ester, R = Et Ph

  27. EWPC 10 – Regensburg – 19/03/13 Catalysis : 2) Optimisation Ph

  28. EWPC 10 – Regensburg – 19/03/13 Catalysis : 2) Optimisation Ph

  29. EWPC 10 – Regensburg – 19/03/13 Conclusion

  30. EWPC 10 – Regensburg – 19/03/13 Conclusion Identification of a good tether

  31. EWPC 10 – Regensburg – 19/03/13 Conclusion Identification of a good tether 2) Good catalyticactivity

  32. EWPC 10 – Regensburg – 19/03/13 Conclusion Identification of a good tether 2) Good catalyticactivity 3) Optimisation of the enantioselectivity

  33. EWPC 10 – Regensburg – 19/03/13 Perspectives • New organocatalyticreactions • Phosphoramidites and organometalliccatalysis

  34. EWPC 10 – Regensburg – 19/03/13 Aknowledgement ANR-11-BS07-002-01 : CHIRACID Dr. A. Marinetti Dr. J.F. Betzer Dr. A. Voituriez Dr. X. Guinchard Kévin Isaac Yang Zhang Julien Pastor KeihannYavari Maxime Gicquel Paul Aillard Valérian Gobé Dr F. Nuter Cristallography Dr. Pascal Retailleau HPLC Odile Thoison Suzanna Ramos Franck Pelissier ComputationalChemistry Dr. G. Frison

  35. EWPC 10 – Regensburg – 19/03/13 Aknowledgement …and you for listening !

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