SlideServe
Télécharger Obtenir Pro
Menu
Accueil Pro
Préférences
ApparenceLight Aide et commentaires
© SlideServe · v2026

Enantioselective Formation of Quaternary Carbon Centers

Jims avatar
Jims
54 diapositives · 1K Views · Nov 14, 2011

Enantioselective Formation of Quaternary Carbon Centers. Cory C. Bausch November 18, 2004. Outline. Introduction Types of Reactions Alkylations Diels-Alder Cyclopropanation Pd Catalyzed Reactions Chiral Transfer Reactions Summary. Introduction.

#asymmetric #carbonic #hydrochloride #hydrosulphate #thiazine #base #photosynthesis #transcendental meditation
Enantioselective Formation of Quaternary Carbon Centers - slide 1
01 / 54Enantioselective Formation of Quaternary Carbon Centers
1 / 17

Télécharger la présentation

Enantioselective Formation of Quaternary Carbon Centers
Une image / un lien ci-dessous est fourni (tel quel) pour télécharger la présentation

Politique de téléchargement : le contenu du site vous est fourni TEL QUEL pour votre information et votre usage personnel ; il ne peut être vendu, concédé sous licence ni partagé sur d’autres sites sans l’accord de son auteur.Le contenu vous est fourni TEL QUEL, pour votre information et votre usage personnel uniquement. Téléchargez la présentation en cliquant sur ce lien. Lors du téléchargement, si vous ne parvenez pas à télécharger une présentation, l’éditeur a peut-être supprimé le fichier de son serveur.Pendant le téléchargement, si vous ne parvenez pas à obtenir une présentation, le fichier a peut-être été supprimé par l’éditeur.

F I N

Plus de contenu associé

Transcription de la présentation

  1. Enantioselective Formation of Quaternary Carbon Centers Cory C. Bausch November 18, 2004

  2. Outline • Introduction • Types of Reactions • Alkylations • Diels-Alder • Cyclopropanation • Pd Catalyzed Reactions • Chiral Transfer Reactions • Summary

  3. Introduction • Chiral quaternary center: Carbon with four different non-hydrogen substituents • Quaternary Center in this context: Carbon with four non-equivalent carbon substituents

  4. Synthetic Targets

  5. Outline • Introduction • Types of Reactions • Alkylations • Diels-Alder • Cyclopropanation • Pd Catalyzed Reactions • Chiral Transfer Reactions • Summary

  6. a,a-Alkylated Ketones a) Based on optical rotation of pure enantiomer Shun-ichi Hashimoto and Kenji Koga Tetrahedron Lett. 1978, 6, 573

  7. Tandem Michael Addition/Aldol Kogen, H.; Tomioka, K.; Hashimoto, S.; Koga, K.Tetrahedron Lett. 1980, 21, 4005

  8. Scope of Addition/Alkylation Kogen, H.; Tomioka, K.; Hashimoto, S.; Koga, K.Tetrahedron Lett. 1980, 21, 4005 Kogen, H.; Tomioka, K.; Hashimoto, S.; Koga, K. Tetrahedron1981, 37, 3951

  9. Alkylation of b-Keto Esters • Achieve both enantiomers with the same chiral species • Binding properties of ligand affect orientation of enamine Tomioka, K.; Ando, K.; Takemasa, Y. Koga, K. J. Am. Chem. Soc. 1984, 106, 2718

  10. Orientation of Addition • THF is poor coordinating ligand • HMPA is strong coordinating ligand Tomioka, K.; Ando, K.; Takemasa, Y. Koga, K. Tetrahedron Lett. 1984, 25, 5677

  11. Scope of Alkylation Tomioka, K.; Ando, K.; Takemasa, Y. Koga, K. J. Am. Chem. Soc. 1984, 106, 2718

  12. Chiral Phase Transfer Catalysis Hermann, K. and Wynberg, H. J. Org. Chem. 1979, 44, 2238

  13. PTC, cont. • Reaction gives up to 95% yield, 92% ee Dolling, U.H.; Davis, P.; Grabowski, E.J. J. Am. Chem. Soc. 1984, 106, 446

  14. PTC, cont. • Convenient, efficient Robinson annulation. • Product can be obtained in 78% ee and 99% yield. Dolling, U.H., et al. Angew. Chem. Int. Ed. Engl. 1986, 25, 476

  15. Nucleophilic Chiral Pd Enolates • Works for b-keto esters as well • Reaction scope gives 69-92% yield and 89-93% ee Hamashima, Y.; Hotta, D.; Sodeoka, M. J. Am. Chem. Soc. 2002, 124, 11240

  16. Salen-Al Catalyzed Michael Additions Taylor, M.S. and Jacobsen, E.N. J. Am. Chem. Soc. 2003, 125, 11204

  17. Outline • Introduction • Types of Reactions • Alkylations • Diels-Alder • Cyclopropanation • Pd Catalyzed Reactions • Chiral Transfer Reactions • Summary

  18. Enantioselective Diels Alder Cycloadditions • Reaction scope gives 40-91% yield and 82-96% ee Furuta, K.; Shimizu, S.; Miwa, Y.; Yamamota, H. J. Org. Chem. 1989, 54, 1481

  19. Cr(III)-Salen Catalyzed Enantioselective Diels-Alder Huang, Y.; Iwama, T.; Rawal, V.H. J. Am. Chem. Soc. 2000, 122, 7843

  20. Cr(III)-Salen Catalyzed, cont. Huang, Y.; Iwama, T.; Rawal, V.H. J. Am. Chem. Soc. 2000, 122, 7843

  21. Cr(III)-Salen Catalyzed, cont. Huang, Y.; Iwama, T.; Rawal, V.H. J. Am. Chem. Soc. 2000, 122, 7843

  22. Advances of Cr(III)-Salen Catalyzed Diels-Alder • Preserves second stereocenter • Possesses more functionality • General reaction scope • Mild and convenient conditions Huang, Y.; Iwama, T.; Rawal, V.H. Org. Lett. 2002, 4, 1163

  23. Rare-Earth Metal Catalyzed Quinone Diels-Alder • New effective chiral lewis acid in quinone Diels-Alder reactions • Sm, Gd are optimal metals from lanthanide metal screen Evans, D.A. and Wu, J. J. Am. Chem. Soc. 2003, 125, 10162

  24. Quinone Diels-Alder Reaction Evans, D.A. and Wu, J. J. Am. Chem. Soc. 2003, 125, 10162

  25. Application of Enantioselective Diels-Alder • Key step in the synthesis of Aspidosperma alkaloids • Generates two key stereocenters in one step • Synthesis gives >95% ee in 12 overall steps • Can be completed on >1 g scale Kozmin, S.A.; Iwama, T.; Huang, Y.; Rawal, V.H. J. Am. Chem Soc. 2002, 124, 4628

  26. Further Applications • Diels-Alder sets stereocenter in high ee • Efficient synthesis of 6-membered ring backbone Corey, E.J.; Guzman-Perez, A.; Teck-Peng, L. J. Am. Chem. Soc. 1994, 116, 3611

  27. Outline • Introduction • Types of Reactions • Alkylations • Diels-Alder • Cyclopropanation • Pd Catalyzed Reactions • Chiral Transfer Reactions • Summary

  28. Enantioselective Cyclopropanation • Asymmetric Modified Simmons-Smith Reaction • Reported in 1985 by Yamamoto, et al. and Mash, et al. Arai, I.; Mori, A.; Yamamoto, H. J. Am. Chem. Soc. 1985, 107, 8254 Mash, E.A. and Nelson, K.A. J. Am. Chem. Soc. 1985, 107, 8256

  29. Cyclopropanation, cont. Arai, I.; Mori, A.; Yamamoto, H. J. Am. Chem. Soc. 1985, 107, 8254 Mash, E.A. and Nelson, K.A. J. Am. Chem. Soc. 1985, 107, 8256

  30. Cyclopropanation in Total Synthesis • Cyclopropanation in 84% yield, 89% ee • 15% overall yield in 14 Steps Mash, E.A.; Math, S.K.; Flann, C.J. Tetrahedron Lett. 1988, 29, 2147

  31. Cyclopropanation of Allylic Alcohols • General substrate scope • No stoichiometric chiral source necessary • Order of addition of reagents is important Denmark, S.E. and O’Connor, S.P. J. Org. Chem. 1997, 62, 584

  32. Outline • Introduction • Types of Reactions • Alkylations • Diels-Alder • Cyclopropanation • Pd Catalyzed Reactions • Chiral Transfer Reactions • Summary

  33. Pd-Catalyzed Heck Reactions • Thoroughly explored pathway to quaternary carbons • Reaction is enantioselective and catalytic Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54, 4738

  34. Heck Reactions • Cis-decalin derivatives among first systems studied Sato, Y.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1989, 54, 4738

  35. Heck Reactions • Improvements using vinyl triflates • No silver salt needed • Higher enantiomeric excess obtained Sato, Y.; Watanabe, S.; Shibasaki, M. Tetrahedron Lett. 1992, 33, 2589

  36. Heck Reactions • Synthesis of hydrindans Sato, Y.; Honda, T.; Shibasaki, M. Tetrahedron Lett. 1992, 33, 2593

  37. Heck-Type Reactions • Palladium catalyzed polyene cyclizations of trienyl triflates Carpenter, N.E.; Kucera, D.J.; Overman, L.E. J. Org. Chem. 1989, 54, 5846

  38. Application of Polyene Cyclization • Enantioselective total synthesis • Heck reaction unsuccessful, polyene cyclization works well Maddaford, S.P.; Anderson, N.G.; Cristofoli, W.A.; Keay, B.A. J. Am. Chem. Soc. 1996, 118, 10766

  39. Heck Reaction, cont. • Form enantioenriched spirocycles • Achieve either enantiomer with same catalyst Ashimori, A.; Bachand, B.; Overman, L.E.; Poon, D.J. J. Am. Chem. Soc. 1998, 120, 6477

  40. Enantioenriched Spirocycles • Silver salt works better than amine base • Scope is fairly general Ashimori, A.; Bachand, B.; Overman, L.E.; Poon, D.J. J. Am. Chem. Soc. 1998, 120, 6477

  41. Enantioenriched Natural Products • Heck cyclization can obtain either enantiomer Matsuura, T.; Overman, L.E.; Poon, D.J. J. Am. Chem. Soc. 1998, 120, 6500

  42. Synthesis of Vicinal Stereogenic Quaternary Carbon Centers Overman, L.E.; Paone, D.V.; Stearns, B.A. J. Am. Chem. Soc. 1999, 121, 7702

  43. Vicinal Quaternary Centers, cont. • Both products formed with complete stereocontrol • Variation in protecting group allows access to both stereogenic products Overman, L.E.; Paone, D.V.; Stearns, B.A. J. Am. Chem. Soc. 1999, 121, 7702

  44. Further Expansion of Heck Coupling Lebsack, A.D.; Link, J.T.; Overman, L.E.; Stearns, B.A. J. Am. Chem. Soc. 2002, 124, 9008

  45. Pd-Catalyzed Allylation • Chiral ferrocenylphosphine ligands among first used • Works for wide array of b-diketones Hayashi, T.; Kanehira, K.; Hagihara, T.; Kumada, M. J. Org. Chem. 1988, 53, 113

  46. Pd-Catalyzed Allylation Trost, B.M.; Radinov, R.; Grenzer, E.M. J. Am. Chem. Soc. 1997, 119, 7879 Trost, B.M.; Schroeder, G.M. J. Am. Chem. Soc. 1999, 121, 6759

  47. Enantioselective Tsuji Allylation Behenna, D.C. and Stoltz, B.M. J. Am. Chem. Soc. ASAP

  48. Tsuji Allylation, cont. • Catalytic cycle of racemic allylation Behenna, D.C. and Stoltz, B.M. J. Am. Chem. Soc. ASAP Tsuji, J. and Minami, I. Acc. Chem. Res. 1987, 20, 140

  49. Outline • Introduction • Types of Reactions • Alkylations • Diels-Alder • Cyclopropanation • Pd Catalyzed Reactions • Chiral Transfer Reactions • Summary

  50. Chiral Transfer Reactions • Chirality transfer based on thermodynamic stability Hiroi, K.; Nakamura, H.; Anzai, T. J. Am. Chem. Soc. 1987, 109, 1249