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" consisting of carbon, hydrogen, sulfur and other nonmetal elements found in organic compounds.

Quotes

• In biological systems, hydrogen bonding is used extensively for molecular recognition, substrate binding, orientation and activation. In organocatalysis, multiple hydrogen bonding by man-made catalysts can effect remarkable accelerations and selectivities as well.
  • A. Berkessel, "Organocatalysis by Hydrogen Bonding Networks" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• By using related Mannich reactions it was also possible to open up a flexible entry to amino sugars, carbasugars, polyoxamic acid and phytosphingosine derivatives. Furthermore, novel ulosonic acid precursors were obtained via an organocatalytic entry. The concept was extended to multicomponent cascade reactions leading to tetrasubstitued cyclohexene carbaldehydes. (...) Starting from diene containing aldehyde substrates the organocatalytic domino process could be combined with an intramolecular Diels-Alder reaction in one pot providing tricyclic carbon frameworks under control of five carboncarbon bonds and up to eight stereocenters.
  • D. Enders, M. R. M. Hüttl, and O. Niemeier. "Biomimetic organocatalytic C–C-bond formations." in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• Four recent developments in reaction methodology—two of them being organocatalytic reactions—now allow for a very efficient access to UCS1025A. (...) We have developed a straightforward strategy for the synthesis of an important class of lepidopteran sex pheromones starting from simple dialdehydes. The combination of a Wittig reaction and an organocatalytic reduction represents a useful sequence for the nontrivial two-carbon homologation of aldehydes. (...) In the early stages of the UCS1025A campaign, we developed a novel two-step approach to small N-heterocycles using an organocatalytic Mannich reaction and a novel CDI-mediated dehydrative cyclization. (...) Our work and that of others have clearly demonstrated that organocatalytic strategies can cut down the total number of synthetic operations.
  • D. Enders, M. R. M. Hüttl, and O. Niemeier. "Biomimetic organocatalytic C–C-bond formations." in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• Organocatalysis offers several advantages not only with respect to its synthetic range. Among “typical” advantages of organocatalysis, in particular with respect to large-scale applications, are favorable economic data of many organocatalysts, the stability of organocatalysts as well as the potential for an efficient recovery
  • Harald Gröger, "Asymmetric organocatalysis on a technical scale: current status and future challenges." in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• The suitability of organocatalytic reactions for larger-scale production processes of chiral building blocks has also already been demonstrated in some cases. Notably, different types of bond formation have been reported, comprising several carbon-carbon bond formations as well as oxidation processes. … The Hajos–Parrish–Eder–Wiechert–Sauer reaction certainly represents a historical landmark in the field of (asymmetric) organocatalysis. … A further strength of organocatalysis is its use for efficient carbon–carbon bond formation by means of alkylation processes. … Further great advancements in the field of asymmetric alkylation reactions have been made by several groups for the chiral phase transfercatalyzed alkylation of glycinates. This type of reaction offers attractive access to enantiomerically pure, particularly nonproteinogenic α-amino acids. … The asymmetric catalytic Strecker reaction is another elegant approach for the synthesis of optically active α-amino acids. … Epoxidation reactions belong to the most important (asymmetric) transformations. Besides asymmetric metal-catalyzed methodologies, analogous organocatalytic epoxidation has been known for a long time. … In addition to the Julia–Colonna epoxidation, also the Shi-epoxidation received commercial interest.
  • Harald Gröger, "Asymmetric organocatalysis on a technical scale: current status and future challenges." Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• The results demonstrate that organocatalysis can represent a valuable tool for solutions on industrial scale also. Albeit the use of organocatalysis in industry is still limited, it can be expected that the broad variety of already developed efficient organocatalytic syntheses, in combination with further breakthroughs and new applications, will contribute to an increasing number of organocatalytic large-scale reactions in the future.
  • Harald Gröger, "Asymmetric organocatalysis on a technical scale: current status and future challenges." Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• … in organocatalysis, a purely organic and metal-free small molecule is used to catalyze a chemical reaction. In addition to enriching chemistry with another useful strategy for catalysis, this approach has some important advantages. Small organic molecule catalysts are generally stable and fairly easy to design and synthesize. They are often based on nontoxic compounds, such as sugars, peptides, or even amino acids, and can easily be linked to a solid support, making them useful for industrial applications. However, the property of organocatalysts most attractive to organic chemistsmay be the simple fact that they are organic molecules.
  • S.C. Pan, B. List, "New Concepts for Organocatalysis" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• Enamine catalysis often delivers valuable chiral compounds such as alcohols, amines, aldehydes, and ketones. Many of these are normally not accessible using established reactions based on transition metal catalysts or on preformed enolates or enamines, illustrating the complimentary nature of organocatalysis and metallocatalysis.
  • S.C. Pan, B. List, "New Concepts for Organocatalysis" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• In the proline-based enamine catalysis, proline actually plays a dual role. The amino-group of proline acts as Lewis base, whereas the carboxylic group acts as a Brønsted acid …
  The potential of using relatively strong chiral organic Brønsted acids as catalysts (Specific Brønsted acid catalysis) has been essentially ignored over the last decades. Achiral acids such as p-TsOH have been used as catalysts for a variety of reactions since a long time, but applications in asymmetric catalysis havebeen extremely rare.
  • S.C. Pan, B. List, "New Concepts for Organocatalysis" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• Enamine catalysis, Brønsted acid catalysis, and iminium catalysis turn out to be powerful new strategies for organic synthesis. (...) Despite its long roots, asymmetric organocatalysis is a relatively new and explosively growing field that, without doubt, will continue to yield amazing results for some time to come.
  • S.C. Pan, B. List, "New Concepts for Organocatalysis" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• Due to the increasing number of chiral drugs in the pipeline, asymmetric synthesis and efficient chiral separation technologies are steadily gaining in importance. Recently a third class of catalysts, besides the established enzymes and metal complexes, has been added to the tool kit of catalytic asymmetric synthesis: organocatalysts, small organic molecules in which a metal is not part of the active principle.
  • Manfred T. Reetz, et al. "Preface" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• The renaissance of organocatalysis since 2000 is truly impressive (Berkessel and Gröger 2004; Seayad and List 2005) (see also the other chapters in this monograph). Much of the design of organocatalysts for a variety of different reaction types is inspired by the knowledge that has accumulated regarding the mechanisms of enzyme catalysis. It has been estimated that about 40% of all enzymes are metalloenzymes, while the majority (60%) unfold their catalytic power in the absence of transition metals. Thus, the latter can be considered to be organocatalytic enzymes.
  • Manfred T. Reetz, "Controlling the Selectivity and Stability of Proteins by New Strategies in Directed Evolution: The Case of Organocatalytic Enzymes", in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.

• In summary, in the first 3 years of our research we have made important contributions to the field of organocatalysis. In this highly competitive and fast moving topical area of organic chemistry we have set important milestones by, for example, developing the first metal-free, highly enantioselective Brønsted catalyzed biomimetic transferhydrogenations, cascade reductions, Strecker reactions, azaenamine additions, direct Mannich reactions, pyridine reductions, as well as domino Mannich-Michael additions. The enantioselectivities observed for such transformations are impressive with most exceeding 90% enantiomeric excess. In addition to these novel chiral ion pair catalyzed transformations, we were the first to realize that chiral Brønsted acids can activate carbonyl groups which resulted in the development of the first organocatalytic electrocyclic reactions. This is not only the first example of such a method but more significantly, it opens the door for many further enantioselective carbonyl transformations.
  • M. Rueping, E. Sugiono, "New Developments in Enantioselective Brønsted Acid Catalysis: Chiral Ion Pair Catalysis and Beyond" in Organocatalysis (2008) edited by M.T. Reetz, B. List, S. Jaroch, H. Weinmann.