1 / 65

Gregory C. Fu

“From Planarity to Chirality ” The research work of Gregory C. Fu by Maude Poirier October 2 nd , 2007. Gregory C. Fu. 1963 Born in Galion, Ohio 1984-1985 Researcher with Professor K. Barry Sharpless    MIT 1985-1991 Graduate student with Professor David A. Evans    Harvard University

lovey
Télécharger la présentation

Gregory C. Fu

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. “From Planarity to Chirality”The research work of Gregory C. FubyMaude PoirierOctober 2nd, 2007

  2. Gregory C. Fu • 1963 Born in Galion, Ohio • 1984-1985 Researcher with Professor K. Barry Sharpless   MIT • 1985-1991Graduate student with Professor David A. Evans   Harvard University • 1991-1993 Postdoctoral fellow with Professor Robert H. Grubbs   CALTECH • 1993-1996 Assistant Professor of Chemistry   MIT • 1996-1998 Firmenich Assistant Professor of Chemistry   MIT • 1998-1999 Firmenich Associate Professor of Chemistry   MIT • 1999-present Professor of Chemistry   MIT

  3. Gregory C. Fu • 1963 Born in Galion, Ohio • 1984-1985 Researcher with Professor K. Barry Sharpless   MIT • 1985-1991Graduate student with Professor David A. Evans   Harvard University • 1991-1993 Postdoctoral fellow with Professor Robert H. Grubbs   CALTECH • 1993-1996 Assistant Professor of Chemistry   MIT • 1996-1998 Firmenich Assistant Professor of Chemistry   MIT • 1998-1999 Firmenich Associate Professor of Chemistry   MIT • 1999-present Professor of Chemistry   MIT

  4. Gregory C. Fu • 2007 Fellow, American Academy of Arts and Sciences • 2007 Catalysis Science Award, Mitsui Chemicals   • 2006 Mukaiyama Award, Society of Synthetic Organic Chemistry of Japan   • 2005 Fellow, Royal Society of Chemistry • 2004 Corey Award, American Chemical Society   • 2001 Springer Award in Organometallic Chemistry • 2000 School of Science Undergraduate Teaching Prize, Massachusetts Institute of Technology  • 2000 Chan Memorial Award in Organic Chemistry • 1999 Innovation Recognition Award, Union Carbide  • 1998 Bristol-Myers Squibb Award • 1998 Cope Scholar Award, American Chemical Society  • 1998 Synthetic Organic Chemistry Award, Pfizer  • 1997 Camille Dreyfus Teacher-Scholar Award • 1997 Alfred P. Sloan Research Fellow • 1997 Chemistry Scholar Award, Glaxo Wellcome  • 1996 Lilly Grantee Award, Eli Lilly  • 1996 Cottrell Scholar Award, Research Corporation  • 1995 American Cancer SocietyJunior Faculty Research Award • 1994 National Science FoundationYoung Investigator Award • 1993 Camille and Henry Dreyfus FoundationNew Faculty Award

  5. What is planar chirality ? • Chirality in molecules devoid of chiral centers 1) For the synthesis of cyclophanes see: S. K. Collins, Y. El-Azizi, Pure App. Chem.2006, 78, 783-789. S. K. Collins, Y. El Azizi, A. Schmitzer, Angew. Chem. Int. Ed.2006, 45, 968-973. 2) E. M. Brzostowska, M. Paulynice, R. Bentley, A. Greer, Chem. Res. Toxicol.2007, 20, 1046-1052.

  6. What is planar chirality ? • Chirality in molecules devoid of chiral centers 1) For the synthesis of cyclophanes see: S. K. Collins, Y. El-Azizi, Pure App. Chem.2006, 78, 783-789. S. K. Collins, Y. El Azizi, A. Schmitzer, Angew. Chem. Int. Ed.2006, 45, 968-973. 2) E. M. Brzostowska, M. Paulynice, R. Bentley, A. Greer, Chem. Res. Toxicol.2007, 20, 1046-1052.

  7. What is planar chirality ? • Chirality in molecules devoid of chiral centers 1) For the synthesis of cyclophanes see: S. K. Collins, Y. El-Azizi, Pure App. Chem.2006, 78, 783-789. S. K. Collins, Y. El Azizi, A. Schmitzer, Angew. Chem. Int. Ed.2006, 45, 968-973. 2) E. M. Brzostowska, M. Paulynice, R. Bentley, A. Greer, Chem. Res. Toxicol.2007, 20, 1046-1052.

  8. What is planar chirality ? • Chirality in molecules devoid of chiral centers 1) For the synthesis of cyclophanes see: S. K. Collins, Y. El-Azizi, Pure App. Chem.2006, 78, 783-789. S. K. Collins, Y. El Azizi, A. Schmitzer, Angew. Chem. Int. Ed.2006, 45, 968-973. 2) E. M. Brzostowska, M. Paulynice, R. Bentley, A. Greer, Chem. Res. Toxicol.2007, 20, 1046-1052.

  9. Nucleophilic catalyst development G. C. Fu, Acc. Chem. Res, 2000, 33, 412-420.

  10. Nucleophilic catalyst development • Should be electron rich, enhancing the nucleophilicity of the catalyst • It’s steric environment should be tunable • Should lead to robust planar-chiral complexes for maximum versatility and for ease of handling G. C. Fu, Acc. Chem. Res, 2000, 33, 412-420.

  11. Planar-Chiral nucleophilic catalyst synthesis G. C. Fu, Acc. Chem. Res, 2000, 33, 412-420. J. C. Ruble, G. C. Fu, J. Org. Chem. 1996, 61, 7230-7231.

  12. Kinetic resolution, basic principles • Enantiomers react at different rates with other chiral compounds • The more theses rates are fart appart the better is • Selectivity factor s : k( fast-reacting enantiomer ) k( slow-reacting enantiomer ) ^ S = 10 For a review on kinetic resolution, see: H. B. Kagan, J. C. Flaud, Top. Stereochemi. 1988, 18, 249-330.

  13. Kinetic resolution, basic principles DG Rxn coordinates

  14. Kinetic Resolution of Secondary Alcohols • J. C. Ruble, H. A. Latham, G. C. Fu, J. Am. Chem. Soc.1997, 119, 1492-1493. • J. C. Ruble, J. Tweddell, G. C. Fu, J. Org. Chem.1998, 63, 2794-2795. • B. Tao, J. C. Ruble, D. A. Holc, G. C. Fu, J. Am. Chem. Soc,1999, 121, 5091-5092.

  15. Kinetic Resolution of Secondary Alcohols G. C. Fu, Acc. Chem. Res. 2000, 33, 412-420.

  16. Synthesis of Kagan’s ether analogue 1) M. Harmata, M. Kahraman, J. Org. Chem. 1999, 64, 4949-4952.

  17. Kinetic Resolution of Allylic Alcohols • J. C. Ruble, J. Tweddell, G. C. Fu, J. Org. Chem. 1998, 63, 2794-2795. • S. Bellemen-Laponnaz, J. Tweddell, J. C. Ruble, F. M. Breitling, G. C. Fu, Chem. Commun. 2000, 1009-1010.

  18. Epothilone A synthesis 1) S. Bellemen-Laponnaz, J. Tweddell, J. C. Ruble, F. M. Breitling, G. C. Fu, Chem. Commun. 2000, 1009-1010. 2) For the synthesis of Epothilone A, see: S. C. Sinha, C. F. Barbas, III and R. A. Lerner, Proc. Natl. Acad. Sci. USA,1998, 95, 14603.

  19. Epothilone A synthesis 1) S. Bellemen-Laponnaz, J. Tweddell, J. C. Ruble, F. M. Breitling, G. C. Fu, Chem. Commun. 2000, 1009-1010. 2) For the synthesis of Epothilone A, see: S. C. Sinha, C. F. Barbas, III and R. A. Lerner, Proc. Natl. Acad. Sci. USA,1998, 95, 14603.

  20. Kinetic Resolution of Secondary Amines 1) S. Arai, S. Bellemin-Laponnaz, G. C. Fu, Angew. Chem. Int. Ed. 2001, 40, 234-236.

  21. Asymmetric nucleophilic catalysist: Planar-chiral heterocycles B. L. Hodous, J. C. Ruble, G. C. Fu, J. Am. Chem. Soc.1999, 121, 2637-2638.

  22. Asymmetric nucleophilic catalysist: Planar-chiral heterocycles B. L. Hodous, J. C. Ruble, G. C. Fu, J. Am. Chem. Soc.1999, 121, 2637-2638.

  23. Asymmetric nucleophilic catalysist: Planar-chiral heterocycles B. L. Hodous, J. C. Ruble, G. C. Fu, J. Am. Chem. Soc.1999, 121, 2637-2638.

  24. Asymmetric nucleophilic catalysist: Planar-chiral heterocycles B. L. Hodous, J. C. Ruble, G. C. Fu, J. Am. Chem. Soc.1999, 121, 2637-2638.

  25. Asymmetric Staudinger synthesis of b-lactams 1) B. L. Hodous, G. C. Fu, J. Am. Chem. Soc.2002, 124, 1578-1579. 2) E. C. Lee, B. L. Hodous, E. Bergin, C. Shih, G. C. Fu, J. Am. Chem. Soc. 2005, 127, 11586-11587.

  26. Asymmetric Staudinger synthesis of b-lactams 1) B. L. Hodous, G. C. Fu, J. Am. Chem. Soc.2002, 124, 1578-1579. 2) E. C. Lee, B. L. Hodous, E. Bergin, C. Shih, G. C. Fu, J. Am. Chem. Soc. 2005, 127, 11586-11587.

  27. Asymmetric Staudinger synthesis of b-lactams 1) B. L. Hodous, G. C. Fu, J. Am. Chem. Soc.2002, 124, 1578-1579. 2) E. C. Lee, B. L. Hodous, E. Bergin, C. Shih, G. C. Fu, J. Am. Chem. Soc. 2005, 127, 11586-11587.

  28. Building quaternary centers Steglich rearrangement 1) W. Steglich, G. Hofle, Tetrahedron Lett. 1970, 4727-4730. 2) For a review of asymmetric synthesis of quaternary stereocenter, see: E. J. Corey, A. Guzman-Perez, Angew. Chem. Int. Ed. 1998, 37, 388-401. 3) For an overview on the synthesis and significance of a-alkylated a-amino acids, see: T. Wirth, Angew. Chem. Int. Ed. 1997, 36, 225-227.

  29. Rearrangement of O-Acylation azlactone 1) J. C. Ruble, G. C. Fu, J. Am. Chem. Soc. 1998, 120, 11532-11533. 2) J. C. Ruble, J. Tweddell, G. C. Fu, J. Org. Chem, 1998, 63, 3154-3155.

  30. Rearrangement of O-Acylation azlactone 1) J. C. Ruble, G. C. Fu, J. Am. Chem. Soc. 1998, 120, 11532-11533. 2) J. C. Ruble, J. Tweddell, G. C. Fu, J. Org. Chem, 1998, 63, 3154-3155.

  31. Building quaternary centers: synthesis of oxindoles and benzofuranones I. D. Hills, G. C. Fu, Angew.Chem. Int. Ed. 2003, 42, 3921-3924.

  32. Building quaternary centers: synthesis of oxindoles and benzofuranones I. D. Hills, G. C. Fu, Angew.Chem. Int. Ed. 2003, 42, 3921-3924.

  33. Building quaternary centers: synthesis of oxindoles and benzofuranones I. D. Hills, G. C. Fu, Angew.Chem. Int. Ed. 2003, 42, 3921-3924.

  34. Building quaternary centers: synthesis of b-ketoesters A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc.2005, 127, 5604-5607.

  35. Building quaternary centers: synthesis of b-ketoesters A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc.2005, 127, 5604-5607.

  36. Building quaternary centers: synthesis of b-ketoesters Mechanistic studies A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc.2005, 127, 5604-5607.

  37. Building quaternary centers: synthesis of b-ketoesters Mechanistic studies A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc.2005, 127, 5604-5607.

  38. Building quaternary centers: synthesis of b-ketoesters Mechanistic studies A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc.2005, 127, 5604-5607.

  39. Building quaternary centers: synthesis of b-ketoesters Mechanistic studies A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc.2005, 127, 5604-5607.

  40. Planar-chiral Brønsted Acid catalyst B. L. Hodous, G. C. Fu, J. Am. Chem. Soc. 2002, 124, 10006-10007.

  41. Planar-chiral Brønsted Acid catalyst B. L. Hodous, G. C. Fu, J. Am. Chem. Soc. 2002, 124, 10006-10007.

  42. Planar-chiral Brønsted Acid catalyst B. L. Hodous, G. C. Fu, J. Am. Chem. Soc. 2002, 124, 10006-10007.

  43. Planar-chiral Brønsted Acid catalyst • Support for a Brønsted-acid mechanism: • Treatment of the nucleophiles result in protonation of the catalyst and formation of an ion pair. • The reaction rate has 1st order dependence on ketene and catalyst and zero-order dependence on the nucleophile KIE of 5 has been measured for the addition of 1-D-2-cyanopyrrole to ketenes. • The ee of the product is inversely proportional to the concentration of the reaction. • Stereochemical outcome of the reaction can be explained by this pathway. G. C. Fu, Acc. Chem. Res. 2004, 37, 542-547.

  44. Planar-chiral Brønsted Acid catalyst • Support for a Brønsted-acid mechanism: • Treatment of the nucleophiles result in protonation of the catalyst and formation of an ion pair. • The reaction rate has 1st order dependence on ketene and catalyst and zero-order dependence on the nucleophile KIE of 5 has been measured for the addition of 1-D-2-cyanopyrrole to ketenes. • The ee of the product is inversely proportional to the concentration of the reaction. • Stereochemical outcome of the reaction can be explained by this pathway. G. C. Fu, Acc. Chem. Res. 2004, 37, 542-547.

  45. Planar-chiral Brønsted Acid catalyst • Support for a Brønsted-acid mechanism: • Treatment of the nucleophiles result in protonation of the catalyst and formation of an ion pair. • The reaction rate has 1st order dependence on ketene and catalyst and zero-order dependence on the nucleophile KIE of 5 has been measured for the addition of 1-D-2-cyanopyrrole to ketenes. • The ee of the product is inversely proportional to the concentration of the reaction. • Stereochemical outcome of the reaction can be explained by this pathway. G. C. Fu, Acc. Chem. Res. 2004, 37, 542-547.

  46. Planar-chiral Brønsted Acid catalyst • Support for a Brønsted-acid mechanism: • Treatment of the nucleophiles result in protonation of the catalyst and formation of an ion pair. • The reaction rate has 1st order dependence on ketene and catalyst and zero-order dependence on the nucleophile KIE of 5 has been measured for the addition of 1-D-2-cyanopyrrole to ketenes. • The ee of the product is inversely proportional to the concentration of the reaction. • Stereochemical outcome of the reaction can be explained by this pathway. G. C. Fu, Acc. Chem. Res. 2004, 37, 542-547.

  47. Planar-chiral Brønsted Acid catalyst S. L. Wiskur, G. C. Fu, J. Am. Chem. Soc. 2005, 127, 6176-6177.

  48. Planar-chiral Brønsted Acid catalyst K. Dai, T. Nakai, J. A. C. Romero, G. C. Fu, Angew. Chem. Int. Ed. 2007, 46, 4367-4369.

  49. Planar-chiral Brønsted Acid catalyst K. Dai, T. Nakai, J. A. C. Romero, G. C. Fu, Angew. Chem. Int. Ed. 2007, 46, 4367-4369.

  50. Planar-chiral Brønsted Acid catalyst K. Dai, T. Nakai, J. A. C. Romero, G. C. Fu, Angew. Chem. Int. Ed. 2007, 46, 4367-4369.

More Related