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Cyclopropenes An Accessible Precursor to Enantioenriched Compounds

Cyclopropenes An Accessible Precursor to Enantioenriched Compounds. Lucie ZimmerLiterature Meeting December 1st 2009. Cyclopropenes: Naturally Occuring Products. Cyclopropenes: Biologically Active Compounds. Cyclopropenes: Caracteristics. 27.5 kcalmol -1. 53.7 kcalmol -1.

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Cyclopropenes An Accessible Precursor to Enantioenriched Compounds

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  1. CyclopropenesAn Accessible Precursor to Enantioenriched Compounds Lucie ZimmerLiterature Meeting December 1st 2009

  2. Cyclopropenes: Naturally Occuring Products Cyclopropenes: Biologically Active Compounds

  3. Cyclopropenes: Caracteristics 27.5 kcalmol-1 53.7 kcalmol-1 π caracter of the 3-membered ring

  4. Cyclopropenes: Caracteristics 27.5 kcalmol-1 53.7 kcalmol-1 π caracter of the 3-membered ring + πcaracter of the double bond = very reactive especially towards π-philic transition metals

  5. Summary 1. Syntheses of cyclopropenes 1.1 “Racemic” syntheses 1.2 “Enantioselective” syntheses 2. Carbometallation 2.1 From enantioenriched cyclopropenes 2.2 From racemic cyclopropenes 3. Cycloadditions 3.1 Diels-Alder 3.2 (3+2) 3.3 Pauson-Kahn 4. Metathesis

  6. Summary 1. Syntheses of cyclopropenes 1.1 “Racemic” syntheses 1.2 “Enantioselective” syntheses 2. Carbometallation 2.1 From enantioenriched cyclopropenes 2.2 From racemic cyclopropenes 3. Cycloadditions 3.1 Diels-Alder 3.2 (3+2) 3.3 Pauson-Kahn 4. Metathesis

  7. Cyclopropenes: Large Scale Synthesis 1.1.1 From cyclopropanes 52g Bolesov’s method revisited by Rubin, M.; Gevorgyan, V. Synthesis 2004, 2004, 796-800.

  8. Cyclopropenes: Large Scale Synthesis 1.1.2 From Alkynes • No conversion was observed using 6 and 7 in presence of Rh2(OAc)4 • 10 and 12 are obtained in a 10:1 ratio • 12 untouched during the deprotection of 10 Rubin, M.; Gevorgyan, V. Synthesis 2004, 2004, 796-800.

  9. Cyclopropenes: Enantioselective Synthesis 1.2.1 Kinetic resolution Breslow, R.; Douek, M. J. Am. Chem. Soc. 1968, 90, 2698-2699. Liao, L.-a.; Zhang, F.; Dmitrenko, O.; Bach, R. D.; Fox, J. M. J. Am. Chem. Soc. 2004, 126, 4490-4491.

  10. Cyclopropenes: Enantioselective Synthesis 1.2.2 First enantioselective synthesis Significance of the diazo Significance of the polarity of the diazo (e.g. hexyne, dimethylbutyne) Protopopova, M. N.; Doyle, M. P.; Müller, P.; Ene, D. J. Am. Chem. Soc. 1992, 114, 2755-2757. Imogaï, H.; Bernardinelli, G.; Gränicher, C.; Moran, M.; Rossier, J.-C.; Müller, P. Helv. Chim. Acta 1998, 81, 1754-1764.

  11. Cyclopropenes: Enantioselective Synthesis Lou, Y.; Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 8916-8918. Lou, Y.; Remarchuk, T. P.; Corey, E. J. J. Am. Chem. Soc. 2005, 127, 14223-14230.

  12. Cyclopropenes: Enantioselective Synthesis Quaternary center formation Davies, H. M. L.; Lee, G. H. Org. Lett. 2004, 6, 1233-1236.

  13. Cyclopropenes: Enantioselective Synthesis Marek, I.; Simaan, S.; Masarwa, A. Angew. Chem., Int. Ed. 2007, 46, 7364-7376.

  14. Cyclopropenes: Large Scale Synthesis Cyclopropanation vs Cyclopropenation Doyle, M. P.; Ene, D. G.; Peterson, C. S.; Lynch, V. Angew. Chem., Int. Ed. 1999, 38, 700-702.

  15. Summary 1. Syntheses of cyclopropenes 1.1 “Racemic” syntheses 1.2 “Enantioselective” syntheses 2. Carbometallation 2.1 From enantioenriched cyclopropenes 2.2 From racemic cyclopropenes 3. Cycloadditions 3.1 Diels-Alder 3.2 (3+2) 3.3 Pauson-Kahn 4. Metathesis

  16. Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117-3179.

  17. Cyclopropenes: Carbometallation Diastereo- and Enantioselective: • hydrostannylation • silastannylation • stannastanylation • hydroboration • carbocupration • hydrogenation... Key metals Rh Pd H. G. Richey, Jr., R. M. Bension, J. Org. Chem.1980, 45, 5036. Nakamura, M.; Isobe, H.; Nakamura, E. Chem. Rev. 2003, 103, 1295-1326. Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2002, 124, 11566-11567. Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2003, 125, 7198-7199. Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2004, 126, 3688-3689.

  18. Cyclopropenes: Carbometallation Liao, L.-a.; Fox, J. M. J. Am. Chem. Soc. 2002, 124, 14322-14323.

  19. Cyclopropenes: Enantioselective Synthesis Liu, X.; Fox, J. M. J. Am. Chem. Soc. 2006, 128, 5600-5601.

  20. Cyclopropenes: Enantioselective Synthesis MeMgCl sparged with air can be replaced by MeOH (1 équiv.) Good yields Excellent ees 1,2- and 1,2,3-trisubstitued cyclopropanes Liu, X.; Fox, J. M. J. Am. Chem. Soc. 2006, 128, 5600-5601.

  21. Cyclopropenes: Enantioselective Synthesis But only MethylGrignard lead to good enantioselectivities... Liu, X.; Fox, J. M. J. Am. Chem. Soc. 2006, 128, 5600-5601.

  22. Cyclopropenes: Carbometallation Tarwade, V.; Liu, X.; Yan, N.; Fox, J. M. J. Am. Chem. Soc. 2009, 131, 5382-5383.

  23. Cyclopropenes: Carbometallation Tarwade, V.; Liu, X.; Yan, N.; Fox, J. M. J. Am. Chem. Soc. 2009, 131, 5382-5383.

  24. Cyclopropenes: Enantio- Synthesis of Cyclopropanes Sherrill, W. M.; Rubin, M. J. Am. Chem. Soc. 2008, 130, 13804-13809.

  25. Cyclopropenes: Enantio- Synthesis of Cyclopropanes Sherrill, W. M.; Rubin, M. J. Am. Chem. Soc. 2008, 130, 13804-13809.

  26. Cyclopropenes: Enantio- Synthesis of Cyclopropanes Sherrill, W. M.; Rubin, M. J. Am. Chem. Soc. 2008, 130, 13804-13809.

  27. Cyclopropenes: Enantio- Synthesis of Cyclopropanes Sherrill, W. M.; Rubin, M. J. Am. Chem. Soc. 2008, 130, 13804-13809.

  28. Summary 1. Syntheses of cyclopropenes 1.1 “Racemic” syntheses 1.2 “Enantioselective” syntheses 2. Carbometallation 2.1 From enantioenriched cyclopropenes 2.2 From racemic cyclopropenes 3. Cycloadditions 3.1 Diels-Alder 3.2 (3+2) 3.3 Pauson-Kahn 4. Metathesis

  29. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds 3.1 Diels-Alder

  30. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds Cortistatin A Magnus, P.; Littich, R. Org. Lett. 2009, 11, 3938-3941.

  31. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds Endo kinetic preference seems to be eroded by the extremely exothermic relief of the cyclopropenyl ring strain in the transition state of the Diels Alder. LaRochelle, R. W.; Trost, B. M.; Krepski, L. J. Org. Chem. 1971, 36, 1126–1136. Al Dulayymi, A. R.; Al Dulayymi, J. R.; Baird, M. S. Tetrahedron, 2000, 56, 1115–1125. Van Royen, L. A.; Mijngheer, R.; De Clercq, P. J. Tetrahedron 1985, 41, 4667–4680.

  32. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds Magnus, P.; Littich, R. Org. Lett. 2009, 11, 3938-3941.

  33. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds Magnus, P.; Littich, R. Org. Lett. 2009, 11, 3938-3941.

  34. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds 3.2 Cycloaddition (3+2)

  35. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds DeAngelis, A.; Taylor, M. T.; Fox, J. M. J. Am. Chem. Soc. 2009, 131, 1101-1105.

  36. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds DeAngelis, A.; Taylor, M. T.; Fox, J. M. J. Am. Chem. Soc. 2009, 131, 1101-1105.

  37. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds 3.3 Pauson-Kahn

  38. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds Pallerla, M. K.; Fox, J. M. Org. Lett. 2005, 7, 3593-3595.

  39. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds Pallerla, M. K.; Yap, G. P. A.; Fox, J. M. J. Org. Chem. 2008, 73, 6137-6141. Pallerla, M. K.; Fox, J. M. Org. Lett. 2005, 7, 3593-3595.

  40. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds Total Synthesis of (–)-pentalene

  41. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds

  42. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds

  43. Cyclopropenes: Enantio-Synthesis of Cyclic Compounds

  44. Summary 1. Syntheses of cyclopropenes 1.1 “Racemic” syntheses 1.2 “Enantioselective” syntheses 2. Carbometallation 2.1 From enantioenriched cyclopropenes 2.2 From racemic cyclopropenes 3. Cycloadditions 3.1 Diels-Alder 3.2 (3+2) 3.3 Pauson-Kahn 4. Metathesis

  45. Cyclopropenes: Enantio- Synthesis of Aliphatic Compounds Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, 6877-6882. Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2007, 129, 3824-3825.

  46. Cyclopropenes: Enantio- Synthesis of Aliphatic Compounds

  47. Cyclopropenes: Enantio- Synthesis of Aliphatic Compounds Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, 6877-6882.

  48. Cyclopropenes: Enantio- Synthesis of Aliphatic Compounds Hoveyda, A. H.; Lombardi, P. J.; O'Brien, R. V.; Zhugralin, A. R. J. Am. Chem. Soc. 2009, 131, 8378-8379.

  49. Cyclopropenes: Enantio- Synthesis of Aliphatic Compounds Hoveyda, A. H.; Lombardi, P. J.; O'Brien, R. V.; Zhugralin, A. R. J. Am. Chem. Soc. 2009, 131, 8378-8379.

  50. Cyclopropenes: Enantio- Synthesis of Aliphatic Compounds

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