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NHC in Organocatalysis: Thiamine, Homoeneolate, and Redox Reactions

Explore the comprehensive review of N-Heterocyclic Carbene (NHC) applications in organocatalysis. This seminar presentation covers the history, properties, and catalytic cycles of NHC in various reactions like Benzoin Condensation, Stetter Reaction, Diels-Alder Reaction, and activation of ketene. Learn about the prominent role of Thiamine (Vitamin B1) as an important coenzyme in biochemical reactions. Discover insights into asymmetric catalysis, efficient catalyst design, and other applications of NHC. Delve into the synthesis of g-Butyrolactones, b-Amino Acid Esters, and more.

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NHC in Organocatalysis: Thiamine, Homoeneolate, and Redox Reactions

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  1. N-Heterocyclic carbenes : Comprehensive Organocatalysis Review 2010 Seminar Presentation April 1st, 2010 Francis Barabé University of Ottawa Dept. of Chemistry Center for Catalysis Research and Innovation Prof. Louis Barriault

  2. The Program Introduction Thiamine History-Properties Asymetric Catalysis (Benzoin Condensation and Stetter Reaction) Homoenolate Chemistry Internal Redox Reaction Diels-Alder Reaction Activation of ketene

  3. Thiamine diphosphate (TPP) - Nature’s NHC The first water soluble vitamin isolated and described by Casimir Funk in 1912 • Important coenzyme in a number of biochemical reactions • pyruvate dehydrogenase (glycolysis) • acetolactase synthesis (amino acids) Thiamine Vitamin B1

  4. Pyruvate Dehydrogenase complex Three enzymes complex E1- pyruvate dehydrogenase E2- dihydrolipoyl transacetylase E3- dihydrolipoyl dehydrogenase Thiamine CoA(SH) Chem. Rev, 2007, 107, 12-5609 DeTar, D. F.; Westheimer, F. H. J. Am. Chem. Soc. 1959, 81, 175 Notes de cours Substances Naturelles de Pr. Claude Spino

  5. Wohler, F. Liebig. J. Ann. Pharm. 1832, 3, 249-282 Ugai, T.; and al. J. Pharm. Soc. Jpn. 1943, 269 Mizuhara, M.and al. J. Am. Chem. Soc,1954,76, 571 Breslow, R.; J. Am. Chem. Soc. 1958, 3719-3726 Debate on active specie and stability more studied in organometallic chemistry Isolation and caracterization of first NHC by Arduengo and co worker Wanzlick, H.W.; Angew. Chem. Int. Ed. 1962, 75-80 Lemal, D. M.; J. Am. Chem. Soc. 1964, 2518-2519 Wanzlick, H.WAngew. Chem. Int. Ed. 1968, 7, 141-142 Arduengo,J. Am. Chem. Soc. 1991,113, 361-363 Brief History

  6. Richard JACS 2004 126 4366 • More nucleophilic than basic, but remains one of the strongest neutral base known Kind of NHC and his property D. Bourissou, O. Guerret, F. P. Gabbai, G. Bertrand. Chem. Rev. 2000, 100, 39-91.

  7. Insight in The Catalytic Cycle Nolan, S. P.; et al. Angew. Chem. Int. Ed. 2007, 2988-3000

  8. Evolution of Asymetric Version : The Benzoin Condensation Sheehan, J.; et al. J. Am. Chem. Soc. 1966, 3666-3667; Sheehan, J.; et al. J. Org. Chem. 1974, 1196-1199 ; Enders, D.; et al. Helv. Chim. Acta 1996, 1217-1221 ; Leeper, F. J.; et al. J. Chem. Soc., Perkin Trans. 1 1998, 1891-1893 ; Enders, D.; et al. Angew. Chem. Int. Ed. 2002, 1743-1745

  9. Efficient Catalyst Design : Triazolium Salt Houk, K. N.; et al. Proc. Natl. Acad. Sci. U. S. A.2004, 5770-5775 Enders, D.; et al. Acc. Chem. Res. 2004, 534-541

  10. Intramolecular Suzuki et al. J. Am. Chem. Soc. 2003, 125, 8432-8433 • Asymetric Kerr, M. S.; Read de Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2006, 124, 10298-10299. Enders, D.; Niemeier, O.; Balensiefer, T.Angew. Chem. Int. Ed. 2006, 45, 1463-1467. • Macrocyclization Miller, T and al..J. Org. Chem. 2007, 72, 5260 Benzoin Condensation : Intramolecular version

  11. The Stetter Reaction : Michael Addition Stetter, H. Angew. Chem. Int. Ed. 1976, 15, 639 Tius, M. A.; Harrington, P. E. Org. Lett. 1999, 1, 649

  12. Stetter Reaction with unactivated olefin Glorius, F.; et al. J. Am. Chem. Soc. 2009, 191, 14190-14191

  13. Stetter Reaction with unactivated olefin : Conia-ene • Quaternary center formation is tolerated but, substitution of the terminal carbon of the alkene diminishes the reactivity

  14. Homoenolate Chemistry Nolan, S. P.; et al. Angew. Chem. Int. Ed. 2007, 2988-3000

  15. Homoenolate Chemistry • Glorius and Bode have both shown that it is necessary to carefully adjust the steric bulkof the NHC for selective activation of homoenolate

  16. Synthesis of g-Butyrolactones Glorius, F.; et al. Angew. Chem. Int. Ed. 2004, 6205-6208 Bode, J.; et al. J. Am. Chem. Soc. 2004, 14370-14371

  17. Dimerization, if imine isn’t enough reactive • Inhibition, if imine is too much reactive • With the good balance Synthesis of g-Butyrolactames M. He, J. W. Bode, Org. Lett.2005, 7,3131 – 3134. Bode, J. W.; et al. J. Am. Chem. Soc. 2008, 130, 17266

  18. Synthesis of b-Amino Acid Esters Ying, G.Y., and al.Org. Lett. 2008, 10, 953-956

  19. Bamberger Rearrangement :Annulation Ying, J.Y. and al., Org. Lett. 2008, 12, 2333-2336

  20. Synthesis of trans-Substituted Cyclopentene Nair, V.; et al. J. Am. Chem. Soc. 2006, 8736-8737

  21. Synthesis of cis-Substituted Cyclopentene Bode, J. W.; et al. J. Am. Chem. Soc. 2007, 3520-3521

  22. Synthesis of b-lactames Bode, J. W.; et al. J. Am. Chem. Soc. 2008, 418-419

  23. The Program Introduction Thiamine History-Properties Asymetric Catalysis (Benzoin Condensation and Stetter Reaction) Homoenolate Chemistry Internal Redox Reaction Diels-Alder Reaction Activation of ketene

  24. Zeitler, K.,Org. Lett. 2006, 8, 636 Chan, A.; Scheidt, K. A.Org. Lett. 2005, 7, 905-908 Rovis, T. And al. J. Am. Chem. Soc. 2004, 126, 9518-9519 Chow, K. Y.-K.; Bode, J. W. J. Am. Chem. Soc. 2004, 126, 8126-8127. Internal Redox Reaction

  25. Catalytic Enolate for Mannich Reaction Scheidt,K. A. al. J. Am. Chem. Soc. 2009, 128, 18028-18029

  26. Scheidt,K. A. and al..Org. Lett. 2009, 11, 105-108 Other Applications of Internal Redox Reactions Gravel, M., and al,, T.Org. Lett. 2009, 11, 891-893

  27. Internal Redox with Formylcyclopropanes :Synthesis of 3,4-Dihydro-a-pyrone Derivatives You. S-L., and al,, T.Org. Lett. 2009, 11, 1623-1625

  28. Synthesis of b-lactones

  29. Azadiene Diels-Alder Reaction Bode et al. J. Am. Chem. Soc. 2006, 128, 8418-8420

  30. Oxodiene Diels-Alder Reaction Bode et al., Org. Lett. 2008, 10, 3817-3820

  31. [4 + 2] Cycloaddition of Ketenes with Enones Song, Y., and al. J. Org. Chem. 2009,74,7585-7587

  32. [4 + 2] Cycloaddition of Ketenes with N-Benzoyldiazenes L. He, X. Wu, P. L. Shao, S. Ye,, T.Angew. Chem. Int. Ed. 2009, 48, 192-195.

  33. Formal [2+ 2] Cycloaddition of Ketenes L. He, X. Wu, P. L. Shao, S. Ye,, T.J. Org. Chem. 2009, 19, 7585-7589 L. He, X. Wu, P. L. Shao, S. Ye,, T.Org. Lett. 2008, 10, 277-280 L. He, X. Wu, P. L. Shao, S. Ye,, T.Org. Lett. 2008, 10, 4029-4031

  34. The Program Introduction Thiamine History-Properties Asymetric Catalysis (Benzoin Condensation and Stetter Reaction) Homoenolate Chemistry Internal Redox Reaction Diels-Alder Reaction Activation of ketene

  35. Acknowledgements Group members: Prof. Louis Barriault Geneviève Bétournay Kassandra Lepack Daniel Newbury Jason Poulin Boubacar Sow My students Gabriel Bellavance Patrick Levesque Past members Steve Arns Marie-Christine Brochu Éric Beaulieu Christiane Grisé-Bard My sponsors CRSNG University of Ottawa Family Rockstar Hooley’s Chartwell’s and all of you….

  36. Rovis, T.And al. J. Org. Chem. 2008,73,9727 Other Applications of Internal Redox Reactions

  37. Cyclohexanones and cyclopentanones can be accessed and formation of quaternary c center is tolerated Exploring the Scope Enders, D.; et al. Helv. Chim. Acta 1996, 1899-1902 Rovis, T.; et al. J. Am. Chem. Soc. 2002, 124, 10298 Rovis, T.; et al. Synlett 2009, 1189-1207 • Diasteroselective reaction Rovis, T.; et al. J. Am. Chem. Soc. 2005, 127, 6284

  38. Imine as Electrophile You. S-L., and al,, T.Org. Lett. 2009, 11, 3182-3185

  39. Generation of a,b,-Unsaturated Acyl Imidazoliums Ryan, S. J. Candish, L. Luton, D. W..; et al. J. Am. Chem. Soc. 2009, 131, 14176-14177

  40. Rovis, T.And al. J. Am. Chem. Soc. 2005,127,16406

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