ORGANOCATALYSIS

In organic chemistry, the term 'Organocatalysis' (a concatenation of the terms "organic" and "catalyst") refers to a form of catalysis, whereby the rate of a chemical reaction is increased by an organic catalyst referred to as an "organocatalyst" consiting of carbon, hydrogen, sulfur and other nonmetal elements found in organic compounds ^{[2] [3] [4] [5]}. Because of their similarity in composition and description, they are often mistaken as a misnomer for enzymes due to their comparable effects on reaction rates and forms of catalysis involved.
The term "organocatalysis" was created by 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 amine functionality can be described as performing either enamine catalysis (by forming catalytic quantities of an active enamine nucleophile) or 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 asymmetric catalysis, for example the use of proline in aldol reactions,

Contents

Imidazolidinone organocatalysis

Thiourea organocatalysis

Thiourea functionalized organocatalysts

References

Imidazolidinone organocatalysis

A certain class of imidazolidinone compounds (also called 'McMillan catalysts') are suitable catalysts for asymmetric Diels-Alder reactions. The original such compound was derived from the biomolecule phenylalanine in two chemical steps (amidation with methylamine followed by condensation reaction with acetone) which leave the chirality intact ^[6]:
:
For an example of its use: see Asymmetric DA reactions

Thiourea organocatalysis

In nature noncovalent interactions such as hydrogen bonding ("partial protonation") play a crucial role in enzyme catalysis that is characterized by selective substrate recognition (molecular recognition), substrate activation, and enormous acceleration of organic tranformations.
Based on the pioneering exmaninations by Kelly, Etter, Jorgensen, Hine, Curran, Göbel, and De Mendoza (see review articles cited below) on hydrogen bonding interactions of small, metal-free compounds with electron-rich binding sites Schreiner and co-workers peformed series of theoretical and experimental systematic investigations towards the hydrogen-bonding ability of various thiourea derivatives ^{[7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20]}. This purely organic compounds revealed effective acceleration of simple Diels-Alder reaction, act like weak 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

References

1. W. Langenbeck, ''Liebigs Ann.'' '1929', ''469'', 16.
2. Asymmetric Organocatalysis, , , Berkessel, A., Groeger, H., Wiley-VCH, , ISBN 3-527-30517-3
3. Peter I. Dalko, Lionel Moisan, review: "In the Golden Age of Organocatalysis", ''Angew. Chem. Int. Ed.'' '2004', ''43'', 5138–5175
4. Matthew J. Gaunt, Carin C.C. Johansson, Andy McNally, Ngoc T. Vo, review: ''"Enantioselective organocatalysis"'' ''Drug Discovery Today'', '2007', 12(1/2), 8-27
5. Dieter Enders, Christoph Grondal, Matthias R. M. Hüttl, review: ''"Asymmetric Organocatalytic Domino Reactions",'' ''Angew. Chem. Int. Ed.'' '2007', ''46'', 1570–1581
6. 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.
7. 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.
8. 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]
9. H-Bonding Additives Act Like Lewis Acid Catalysts, P. R. Schreiner and A. Wittkopp, , , Org. Lett., 2002
10. Metal-Free, Noncovalent Catalysis of Diels-Alder Reactions by ''Neutral'' Hydrogen Bond Donors in Organic Solvents and in Water, A. Wittkopp and P. R. Schreiner, , , Chemistry - A European Journal, 2003
11. Peter R. Schreiner, review: ''"Metal-free organocatalysis through explicit hydrogen bonding interactions"'', ''Chem. Soc. Rev.'' '2003', ''32'', 289-296. abstract/download:[2]
12. Acid-free, organocatalytic acetalization, M. Kotke and P. R. Schreiner, , , Tetrahedron, 2006
13. Christian M. Kleiner, Peter R. Schreiner, ''"Hydrophobic amplification of noncovalent organocatalysis"'', ''Chem. Commun.''' 2006', 4315-4017.abstract/download:[3]
14. Generally Applicable Organocatalytic Tetrahydropyranylation of Hydroxy Functionalities with Very Low Catalyst Loading, M. Kotke and P. Schreiner, , , Synthesis, 2007
15. γ-Aminoadamantanecarboxylic Acids Through Direct C-H Bond Amidations, L. Wanka and C. Cabrele, , , European Journal of Organic Chemistry, 2007
16. Thiourea-Catalyzed Transfer Hydrogenation of Aldimines, Z. Zhang and P. R. Schreiner, , , Synlett, 2007
17. Activation of Carbonyl Compounds by Double Hydrogen Bonding: An Emerging Tool in Asymmetric Catalysis, M. P. Petri, , , Angewandte Chemie International Edition, 2004
18. 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]
19.
20. Organocatalysis Mediated by (Thio)urea Derivatives, J. C. Stephen, , , Chemistry - A European Journal, 2006