Presentation is loading. Please wait.

Presentation is loading. Please wait.

1 “From Planarity to Chirality” The research work of Gregory C. Fu by Maude Poirier October 2 nd, 2007.

Similar presentations


Presentation on theme: "1 “From Planarity to Chirality” The research work of Gregory C. Fu by Maude Poirier October 2 nd, 2007."— Presentation transcript:

1 1 “From Planarity to Chirality” The research work of Gregory C. Fu by Maude Poirier October 2 nd, 2007

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

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

4 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 Society Junior Faculty Research Award 1994 National Science Foundation Young Investigator Award 1993 Camille and Henry Dreyfus Foundation New Faculty Award

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

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

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

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

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

10 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,

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

12 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 : S = k( fast-reacting enantiomer ) k( slow-reacting enantiomer ) ^ 10 For a review on kinetic resolution, see: H. B. Kagan, J. C. Flaud, Top. Stereochemi. 1988, 18,

13 13 Kinetic resolution, basic principles GG Rxn coordinates

14 14 Kinetic Resolution of Secondary Alcohols J. C. Ruble, H. A. Latham, G. C. Fu, J. Am. Chem. Soc. 1997, 119, J. C. Ruble, J. Tweddell, G. C. Fu, J. Org. Chem. 1998, 63, B. Tao, J. C. Ruble, D. A. Holc, G. C. Fu, J. Am. Chem. Soc, 1999, 121,

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

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

17 17 Kinetic Resolution of Allylic Alcohols 1) J. C. Ruble, J. Tweddell, G. C. Fu, J. Org. Chem. 1998, 63, ) S. Bellemen-Laponnaz, J. Tweddell, J. C. Ruble, F. M. Breitling, G. C. Fu, Chem. Commun. 2000,

18 18 Epothilone A synthesis 1) S. Bellemen-Laponnaz, J. Tweddell, J. C. Ruble, F. M. Breitling, G. C. Fu, Chem. Commun. 2000, ) 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,

19 19 Epothilone A synthesis 1) S. Bellemen-Laponnaz, J. Tweddell, J. C. Ruble, F. M. Breitling, G. C. Fu, Chem. Commun. 2000, ) 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,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43 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 1 st 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,

44 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 1 st 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,

45 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 1 st 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,

46 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 1 st 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,

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

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

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

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

51 51 Planar-chiral ligands for transition metal-catalyzed reactions H-L. Kwong, W-S. Lee, H-F. Ng, W-H. Chiu, W-T. Wong, J. Chem. Soc. Dalton Trans. 1998, cyclopropanation

52 52 Planar-chiral ligands for transition metal-catalyzed reactions R. Rios, J. Liang, M. M.-C. Lo, G. C. Fu, Chem. Commun. 2000,

53 53 Planar-chiral ligands for transition metal-catalyzed reactions R. Rios, J. Liang, M. M.-C. Lo, G. C. Fu, Chem. Commun. 2000,

54 54 Planar-chiral ligands for transition metal-catalyzed reactions cyclopropanation 1) R. Rios, J. Liang, M. M.-C. Lo, G. C. Fu, Chem. Commun. 2000, ) M. M.-C. Lo, G. C. Fu, J. Am. Chem. Soc. 1998, 120,

55 55 Planar-chiral ligands for transition metal-catalyzed reactions T. C. Maier, G. C. Fu, J. Am. Chem. Soc. 2006, 128, O-H insertion

56 56 Planar-chiral ligands for transition metal-catalyzed reactions E. C. Lee, G. C. Fu, J. Am. Chem. Soc. ASAP N-H insertion

57 57 Planar-chiral ligands for transition metal-catalyzed reactions S. Son, G. C. Fu, J. Am. Chem. Soc. 2007, 129, Asymmetric [4+1] cycloaddition

58 58 Planar-chiral ligands for transition metal-catalyzed reactions M. M-C. Lo, G. C. Fu, J. Am. Chem. Soc. 2002, 124, For mecanism, see: M. Miura, M. Enna, K. Okuro, M. Nomura, J. Org. Chem. 1995, 60, For -lactams trans-isomerization, see: M. Shimizu, K. Kume, T. Fujisawa, Chem. Lett. 1996, -lactams synthesis, the Kinugasa reaction

59 59 Planar-chiral ligands for transition metal-catalyzed reactions M. M-C. Lo, G. C. Fu, J. Am. Chem. Soc. 2002, 124, For mecanism, see: M. Miura, M. Enna, K. Okuro, M. Nomura, J. Org. Chem. 1995, 60, For -lactams trans-isomerization, see: M. Shimizu, K. Kume, T. Fujisawa, Chem. Lett. 1996, -lactams synthesis, the Kinugasa reaction

60 60 Planar-chiral ligands for transition metal-catalyzed reactions M. M-C. Lo, G. C. Fu, J. Am. Chem. Soc. 2002, 124, For mecanism, see: M. Miura, M. Enna, K. Okuro, M. Nomura, J. Org. Chem. 1995, 60, For b-lactams trans-isomerization, see: M. Shimizu, K. Kume, T. Fujisawa, Chem. Lett. 1996, -lactams synthesis, the Kinugasa reaction

61 61 Planar-chiral ligands for transition metal-catalyzed reactions -lactams synthesis, the Kinugasa reaction R. Shintani, G. C. Fu, Angew. Chem. Int. Ed. 2003, 42,

62 62 Planar-chiral ligands for transition metal-catalyzed reactions -lactams synthesis, the Kinugasa reaction R. Shintani, G. C. Fu, Angew. Chem. Int. Ed. 2003, 42,

63 63 Planar-chiral ligands for transition metal-catalyzed reactions -lactams synthesis, the Kinugasa reaction R. Shintani, G. C. Fu, Angew. Chem. Int. Ed. 2003, 42,

64 64 Planar-chiral ligands for transition metal-catalyzed reactions -lactams synthesis, the Kinugasa reaction R. Shintani, G. C. Fu, Angew. Chem. Int. Ed. 2003, 42,

65 65 Conclusion Nucleophilic catalysts Transition-metal ligands Building quaternary centers Brønsted acid catalyst


Download ppt "1 “From Planarity to Chirality” The research work of Gregory C. Fu by Maude Poirier October 2 nd, 2007."

Similar presentations


Ads by Google