Organocatalysis



 

In enzymes due to their comparable effects on reaction rates and forms of catalysis involved.

The term "organocatalysis" was created by David MacMillan in 2000 from the old and well known concept of "organic catalysis" introduced by the German chemist Wolfgang Langenbeck; "organocatalysis" is nothing more than a new name for an old methodology, but thus gives fresh impulses for intensive research in the following years.

Organocatalysts which display secondary iminium catalysis (by forming catalytic quantities of an activated iminium electrophile). This mechanism is typical for covalent organocatalysis. Covalent binding of substrate normally requires high catalyst loading (for proline-catalysis typically 20-30 mol%). Noncovalent interactions such as hydrogen-bonding facilitates low catalyst loadings (down to 0.001 mol%).

Two main advantages of organocatalysis are:

  • there is no need for metal-based catalysis thus making a contribution to green chemistry
  • when the organocatalyst is chiral an avenue is opened to aldol reactions,

Introduction

Regular achiral organocatalysts are based on nitrogen such as Hajos-Parrish-Eder-Sauer-Wiechert reaction:

In this reaction, naturally occurring chiral Robert B. Woodward (1981) [8].


Many chiral organocatalysts are an adaptation of chiral ligands (which together with a metal center also catalyze asymmetric reactions) and both concepts overlap to some degree.

Organocatalyst classes

Organocatalysts for asymmetric synthesis can be grouped in several classes:

  • cinchona alkaloids, certain oligopeptides.
  • Synthetic catalysts derived from biomolecules. Examples of proline derivatives are McMillan Imidazolidinones and the CBS catalyst
  • TADDOLS
  • Derivatives of NOBIN
  • Triazolium salts as next-generation Stetter reaction catalysts
  • Organocatalysts based on thioureas

Examples of asymmetric reactions involving organocatalysts are:

Imidazolidinone organocatalysis

A certain class of imidazolidinone compounds (also called MacMillan organocatalysts) are suitable catalysts for many acetone) which leave the chirality intact [9]:

This catalyst works by forming a iminium ion with LUMO [10]:

The transient iminium intermediate is chiral which is transferred to the reaction product via chiral induction. The catalysts have been used in transfer hydrogenations and epoxidations.

One example is the asymmetric synthesis of the drug benzylideneacetone [11]:

A recent exploit is the organotrifluoroborate salt [12]:

For other examples of its use: see organocatalytic transfer hydrogenation and asymmetric DA reactions.

Thiourea organocatalysis

In nature noncovalent interactions such as catalysis that is characterized by selective substrate recognition (molecular recognition), substrate activation, and enormous acceleration of organic transformations. Based on the pioneering exmaninations by Kelly, Etter, Jorgensen, Hine, Curran, Göbel, and De Mendoza (see review articles cited below) on Lewis acid catalyst, but act through explicit double hydrogen bonding instead of covalent binding known from traditional metal-ion mediated catalysis. Schreiner and co-workers identified and indroduced electron-poor thiourea derivatives as hydrogen-bonding organocatalysts. N,N'-bis[[3,5-bis(trifluormethyl)phenyl thiourea is to date the most effective achiral thiourea derivative and combines all typical structural features for double H-bonding mediated organocatalysis:

  • electron-poor
  • rigid structure
  • non-coordinating, electron withdrawing substituents in 3,4, and/or 5 position of a phenyl ring
  • the trifluoromethyl-group is the preferred substituent

Advantages of thiourea derivatives:

  • no product inhibition due to weak enthalpic binding, but specific binding-“recognition“
  • low catalyst-loading (down to 0.001 mol%)[citation needed]
  • high TOF values (up to 2,000 h–1)[citation needed]
  • simple and inexpensive synthesis
  • easily to modulate and to handle, no inert atmosphere necessary
  • immobilization on solid phase (polymer-bound organocatalysts), catalyst recovery and reusability
  • catalysis under almost neutral conditions (pka thiourea 21.0), acid-sensitive substrates are tolerated
  • metal-free, not toxic (compare traditional metal-containing Lewis-acid catalysts
  • water-tolerant, even catalytically effective in water or aqueous media
  • environmentally benign ("Green Chemistry")

To date various organic transformations are organocatalyzed through hydrogen-bonding N,N'-bis[[3,5-bis(trifluormethyl)phenyl thiourea at low catalyst loadings and in good to excellent product yields. This electron-poor thiourea derivative has proven to be the benchmark for noncovalent organocatalysis utilizing explicit hydrogen-bonding as well as to be the basis for development of a wide range of catalytically active derivatives.

Since 2001 research groups world-wide (e.g., Berkessel, Connon, Jacobsen, Nagaswa, Takemoto) have realized the potential of thiourea derivatives and developed various achiral/chiral mono- and bifunctional derivatives incorporating the electron-poor 3,5-bis(trifluoromethyl)phenyl substrate-"anchor" functionality. Meanwhile a broad spectrum of organic transformations are performed through hydrogen-bonding organocatalysis and the research ist still in the focus of interest.

       
       
       
   

References

  1. ^ Justus von Liebig (1860). "Ueber die Bildung des Oxamids aus Cyan". Annalen der Chemie und Pharmacie 113 (2): 246-247.
  2. ^ W. Langenbeck, Liebigs Ann. 1929, 469, 16.
  3. ^ Berkessel, A., Groeger, H. (2005). Asymmetric Organocatalysis. Weinheim: Wiley-VCH. ISBN 3-527-30517-3. 
  4. ^ Peter I. Dalko, Lionel Moisan, review: "In the Golden Age of Organocatalysis", Angew. Chem. Int. Ed. 2004, 43, 5138–5175
  5. ^ Matthew J. Gaunt, Carin C.C. Johansson, Andy McNally, Ngoc T. Vo, review: "Enantioselective organocatalysis" Drug Discovery Today, 2007, 12(1/2), 8-27
  6. ^ Dieter Enders, Christoph Grondal, Matthias R. M. Hüttl, review: "Asymmetric Organocatalytic Domino Reactions", Angew. Chem. Int. Ed. 2007, 46, 1570–1581
  7. ^ Enantioselective Organocatalysis Peter I. Dalko and Lionel Moisan Angew. Chem. Int. Ed. 2001, 40, 3726 ± 3748
  8. ^ Asymmetric total synthesis of erythromcin. 1. Synthesis of an erythronolide A secoacid derivative via asymmetric induction R. B. Woodward, E. Logusch, K. P. Nambiar, K. Sakan, D. E. Ward, B. W. Au-Yeung, P. Balaram, L. J. Browne, P. J. Card, C. H. Chen J. Am. Chem. Soc.; 1981; 103(11); 3210-3213. doi:10.1021/ja00401a049
  9. ^ New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Diels-Alder Reaction Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc.; (Communication); 2000; 122(17); 4243-4244. doi:10.1021/ja000092s
  10. ^ Modern Strategies in Organic Catalysis: The Advent and Development of Iminium Activation Gérald Lelais and David W. C. MacMillan VOL. 39, NO. 3, 79 • 2006 Aldrichimica Acta http://www.sigmaaldrich.com/aldrich/brochure/al_acta_39_3.pdf
  11. ^ Organocatalytic Asymmetric Michael Reaction of Cyclic 1,3-Dicarbonyl Compounds and ,-Unsaturated Ketones - A Highly Atom-Economic Catalytic One-Step Formation of Optically Active Warfarin Anticoagulant Angewandte Chemie International EditionVolume 42, Issue 40, Date: October 20, 2003, Pages: 4955-4957 Nis Halland, Tore Hansen, Karl Anker Jørgensen doi:10.1002/anie.200352136
  12. ^ Organocatalytic Vinyl and Friedel-Crafts Alkylations with Trifluoroborate Salts Sandra Lee and David W. C. MacMillan J. AM. CHEM. SOC. 2007, 129, 15438-15439 doi:10.1021/ja0767480
  13. ^ Alexander Wittkopp, Peter R. Schreiner, "Diels-Alder Reactions in Water and in Hydrogen-Bonding Environments", book chapter in "The Chemistry of Dienes and Polyenes" Zvi Rappoport (Ed.), Volume 2, John Wiley & Sons Inc.; Chichester, 2000, 1029-1088. ISBN 0-471-72054-2.
  14. ^ Alexander Wittkopp, "Organocatalysis of Diels-Alder Reactions by Neutral Hydrogen Bond Donors in Organic and Aqueous Solvents", dissertation written in German, Universität Göttingen, 2001. english abstract/download: [1]
  15. ^ P. R. Schreiner and A. Wittkopp (2002). "H-Bonding Additives Act Like Lewis Acid Catalysts". Org. Lett. 4 (2): 217-220. doi:10.1021/ol017117s.
  16. ^ A. Wittkopp and P. R. Schreiner (2003). "Metal-Free, Noncovalent Catalysis of Diels-Alder Reactions by Neutral Hydrogen Bond Donors in Organic Solvents and in Water". Chemistry - A European Journal 9 (2): 407-414. doi:10.1002/chem.200390042.
  17. ^ Peter R. Schreiner, review: "Metal-free organocatalysis through explicit hydrogen bonding interactions", Chem. Soc. Rev. 2003, 32, 289-296. abstract/download:[2]
  18. ^ M. Kotke and P. R. Schreiner (2006). "Acid-free, organocatalytic acetalization". Tetrahedron 62 (2-3): 434-439.
  19. ^ Christian M. Kleiner, Peter R. Schreiner, "Hydrophobic amplification of noncovalent organocatalysis", Chem. Commun. 2006, 4315-4017.abstract/download:[3]
  20. ^ M. Kotke and P. Schreiner (2007). "Generally Applicable Organocatalytic Tetrahydropyranylation of Hydroxy Functionalities with Very Low Catalyst Loading". Synthesis (5): 779-790. doi:10.1055/s-2007-965917.
  21. ^ L. Wanka and C. Cabrele (2007). "γ-Aminoadamantanecarboxylic Acids Through Direct C-H Bond Amidations". European Journal of Organic Chemistry 2007 (9): 1474-1490. doi:10.1002/ejoc.200600975.
  22. ^ Z. Zhang and P. R. Schreiner (2007). "Thiourea-Catalyzed Transfer Hydrogenation of Aldimines". Synlett (9): 1455-1457. doi:10.1055/s-2007-980349.
  23. ^ M. P. Petri (2004). "Activation of Carbonyl Compounds by Double Hydrogen Bonding: An Emerging Tool in Asymmetric Catalysis". Angewandte Chemie International Edition 43 (16): 2062-2064. doi:10.1002/anie.200301732.
  24. ^ Yoshiji Takemoto, review: "Recognition and activation by ureas and thioureas: stereoselective reactions using ureas and thioureas as hydrogen-bonding donors", Org. Biomol. Chem. 2005, 3, 4299-4306. abstract/download: [4]
  25. ^ Mark S. Taylor, Eric N. Jacobsen (2006). "Asymmetric Catalysis by Chiral Hydrogen-Bond Donors". Angewandte Chemie International Edition 45 (10): 1520-1543. doi:10.1002/anie.200503132.
  26. ^ J. C. Stephen (2006). "Organocatalysis Mediated by (Thio)urea Derivatives". Chemistry - A European Journal 12 (21): 5418-5427. doi:10.1002/chem.200501076.
v • d • e
Concepts in Biocatalysis
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Organocatalysis". A list of authors is available in Wikipedia.