1 / 42

Feng Shi

Chiral Phosphoric Acids-Catalyzed Multi-Component Reactions for Synthesis of Structurally Diverse Nitrogenous Compounds. Feng Shi. Dec. 18th, 2010. Introduction:. Multi-component Reactions (MCR). The definition of MCR:.

nash-richards
Download Presentation

Feng Shi

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. Chiral Phosphoric Acids-Catalyzed Multi-Component Reactions for Synthesis of Structurally Diverse Nitrogenous Compounds Feng Shi Dec. 18th, 2010

  2. Introduction: Multi-component Reactions (MCR) The definition of MCR: The reaction between three or more reagents in a single vessel which have been added together (or nearly) to form a new compound that contains significant portions of all the components. The advantages of MCR: • superior atom economy, atom utilization and selectivity • lower level of by-products • simpler procedures and equipment • lower costs, time, and energy • more environmentally friendly

  3. Chiral Organocatalyzed Multi-component Reactions • Amino-acid derivatives • Brønsted acids • Lewis bases • Nucleophilic Carbenes Chiral Organocatalysts: Combined catalysis of organo and metal catalysts

  4. Chiral Brønsted Acids For review, see: T. Akiyama*, Chem. Rev.2007, 107, 5744.

  5. Other newly developed Brønsted Acids:

  6. The first examples of Phosphoric Acids-catalyzed Reactions T. Akiyama*, J. Itoh, K. Yokota, K. Fuchibe, Angew.Chem. Int. Ed. 2004, 43, 1566. D. Uraguchi, M. Terada*, J. Am. Chem. Soc.2004, 126, 5356.

  7. The Structural Features of Chiral Phosphoric Acids: For related reviews, see: (a) M. Terada*, Synthesis, 2010, 1929; (b) A. Zamfir, S. Schenker, M. Freund, S. B. Tsogoeva*, Org. Biomol. Chem., 2010, 8, 5262; (c) S. J. Connon*, Angew.Chem. Int. Ed. 2006, 45, 3909.

  8. Chiral Phosphoric Acids-Catalyzed Multi-Component Reactions Aza-D-A Reaction Cyclization Reactions Direct Mannich Reaction Biginelli Reaction Ugi-type reaction 1,3-Dipolar Cycloaddition Povarov Reaction Kabachnik–Fields Reaction Hantzsch Reaction Friedel-Crafts Aminoalkylation

  9. Direct Mannich Reaction: Transition state Q.-X. Guo, H. Liu, C. Guo, S.-W. Luo, Y. Gu, L.-Z. Gong*, J. Am. Chem. Soc.2007, 129, 3790.

  10. Using Enecarbamates as Nucleophiles G. Dagousset, F. Drouet, G. Masson, J. Zhu*, Org. Lett., 2009, 11, 5546.

  11. Vinylogous Mannich Reaction M. Sickert, F. Abels, M. Lang, J. Sieler, C. Birkemeyer, C. Schneider*, Chem. Eur. J.2010, 16, 2806.

  12. Biginelli Reaction: P. G. Biginelli*, Chim. Ital.1893, 23, 360. General mechanism:

  13. The first organocatalytic highly enantioselective Biginelli reaction X.-H. Chen, X.-Y. Xu, H. Liu, L.-F. Cun, L.-Z. Gong*, J. Am. Chem. Soc.2006, 128, 14802.

  14. Biginelli and Biginelli-Like Condensations • Reversal of the stereochemistry by tuning the 3,3’-disubstituents of phosphoric acids N. Li, X.-H. Chen, J. Song, S.-W. Luo*, W. Fan, L.-Z. Gong*, J. Am. Chem. Soc.2009, 131, 15301.

  15. Reaction Mechanism

  16. Synthetic applications:

  17. Asymmetric Amplification in Phosphoric Acid-Catalyzed Biginelli Reaction: • Positive nonlinear effect N. Li, X.-H. Chen, S.-M. Zhou, S.-W. Luo, J. Song, L. Ren, L.-Z. Gong*, Angew. Chem. Int. Ed.2010, 49, 6378.

  18. Cyclization Reactions Leading to Dihydropyridine Derivatives: Synthetic applications: J. Jiang, J. Yu, X.-X. Sun, Q.-Q. Rao, L.-Z. Gong*, Angew. Chem. Int. Ed. 2008, 47, 2458.

  19. Reaction Mechanism:

  20. Cyclization leading to dihydropyridinone derivatives: J. Jiang, J. Qing, L.-Z. Gong*, Chem. Eur. J. 2009, 15, 7031.

  21. Reaction Mechanism: formal [4+2] cycloaddition

  22. Hantzsch reaction: C. G. Evans, J. E. Gestwicki*, Org. Lett.2009, 11, 2957.

  23. Aza-Diels-Alder Reaction: H. Liu, L.-F. Cun, A.-Q. Mi, Y.-Z. Jiang, L.-Z. Gong*, Org. Lett.2006, 8, 6023.

  24. Povarov reaction: An inverse electron-demand aza-Diels-Alder reaction between 2-azadienes and electron-rich olefins. H. Liu, G. Dagousset, G. Masson,* P. Retailleau, J. Zhu*, J. Am. Chem. Soc.2009, 131, 4598.

  25. Ugi-type reaction: T. Yue, M.-X. Wang,* D.-X. Wang, G. Masson, J. Zhu*, Angew. Chem. Int. Ed. 2009, 48, 6717.

  26. 1,3-Dipolar cycloaddition: X.-H. Chen, W.-Q. Zhang, L.-Z.Gong*, J. Am. Chem. Soc. 2008, 130, 5652.

  27. Methyleneindolinones as dipolarophiles to synthesize Spiro[pyrrolidin-3,3’-oxindoles] with unusual regiochemistry X.-H. Chen, Q. Wei, H. Xiao, S.-W. Luo, L.-Z. Gong*, J. Am. Chem. Soc. 2009, 131, 13819.

  28. Reaction mechanism:

  29. Imine as dipolarophile to synthesize imidazolidines W.-J. Liu, X.-H.Chen, L.-Z. Gong*, Org. Lett.2008, 10, 5357.

  30. 2,3-Allenoate as dipolarophiles to create pyrrolidines along with C=C double bond ‘ ‘ J. Yu, L. He, X.-H. Chen, J. Song, W.-J.Chen, L.-Z. Gong*, Org. Lett.2009, 11, 4946. Kinetic Resolution of Racemic 2,3-Allenoates J. Yu, W.-J. Chen, L.-Z. Gong*, Org. Lett.2010, 12, 4050.

  31. 1,4-Naphthoquinone as dipolarophile to synthesize isoindolines C. Wang, X.-H. Chen, S.-M. Zhou, L.-Z. Gong*, Chem. Commun. 2010, 1275.

  32. Kabachnik–Fields reaction: The reaction of a carbonyl compound, an amine, and a phosphite by in situ imine hydrophosphonylation. X. Cheng, R. Goddard, G. Buth, B. List*, Angew. Chem. Int. Ed.2008, 47, 5079. L. Wang, S.-M. Cui, W. Meng, G.-W. Zhang, J. Nie, J.-A. Ma*, Chin. Sci. Bull. 2010, 55, 1729.

  33. Friedel-Crafts aminoalkylation: G.-W. Zhang, L. Wang, J. Nie, J.-A. Ma*, Adv. Synth. Catal.2008, 350, 1457.

  34. Combined catalysis of phosphoric acid and metal catalysts: Cooperative Catalysis Relay Catalysis

  35. Cooperative Catalysis: Mannich-type multi-component reaction: W. Hu*, X. Xu, J. Zhou, W.-J. Liu, H. Huang, J. Hu, L. Yang, L.-Z. Gong*, J. Am. Chem. Soc.2008, 130, 7782.

  36. Reaction mechanism:

  37. X. Xu, J. Zhou, L. Yang, W. Hu*, Chem. Commun.2008, 48, 6564. X. Xu, Yu Qian, L. Yang, W. Hu*, Chem. Commun. ASAP, DOI: 10.1039/c0cc03024d

  38. Relay Catalysis : Consecutive Intramolecular Hydroamination/ Asymmetric Transfer Hydrogenation Z.-Y. Han, H. Xiao, X.-H. Chen, L.-Z. Gong*, J. Am. Chem. Soc.2009, 131, 9182.

  39. Intermolecular Hydroamination and Transfer Hydrogenation Reactions X.-Y. Liu, C.-M. Che*, Org. Lett., 2009, 11, 4204.

  40. Povarov reaction and subsequent intramolecular hydroamination C. Wang, Z.-Y. Han, H.-W. Luo, L.-Z. Gong*, Org. Lett., 2010, 12, 2266.

  41. Conclusions 1. Many asymmetric multi-component reactions have been successfully established by chiral PA. 2. Tremendous progress has been made in the development of chiral PA catalysts. 3. Combined catalysis of PA and metal catalysts is a new orientation. Outlook 1. There are still numerous multi-component reactions to be transformed into their asymmetric versions. 2. Further elaboration of novel PA derived from other types of chiral backbones is needed. 3. A more detailed mechanistic understanding of PA catalysis is needed. 4. It is full of challenge and opportunity to develop combined catalysis of PAand metal catalysts.

  42. Sincere thanks for your attention and kind help!

More Related