Organocatalysis
Ξ July 14th, 2008 | → | ∇ Senza categoria |
What is an organocatalyst? The process of acceleration of chemical reaction with a substoichiometric amount of organic molecule which doesn’t contain metal atoms. The pioneering reaction published in the 1970s is the Hajos-Parrish-Eder-Sauer-Wiechert reaction, the Robinson annulation catalyzed by L-proline.
Several reactions mechanism for the triketone reaction have been proposed over the years; the most important are the Agnami mechanism and the Houk mechanism. The Agnami mechanism has an enamine intermediate with two molecules of proline involved in the transition state, but the most quote mechamisn has been proposed by Houk, where a single proline unit suffices with a cyclic transition state and the proline carboxyl group involved in hydrogen bonding.
List and Barbas in the 2000 have proposed a reaction mechanism based on enamino formation; the observed stereoselectivity based on the Zimmerman-Traxler model favoring the Re-face approach.
The catalytic potential of proline in asymmetric aldol reaction was not explored furher until recently; now thanks to the work of List, MacMillan, and others in the early 2000s, the last ten years have seen exponential growth in the field of asymmetric organocatalysis. New imminium and enamine-based organocatalysis now enables cycloadditions, Micheal additions, Mannich and aldol reactions, nucleophilic substitutions, oxidation and reduction and many other transformations with excellent enantioselectivity; new generation of phase transfer catalyst give almost perfect enantiomeric excesses at low catalyst loadings; chiral ureas and thioureas are extremely enantioselective catalyst for addition of a variety of nucleophiles to aldehydes and imines; and so forth. Organocatalysis currently seems to be in a state of GOLD RUSH and at short intervals new GOLD MINES are discovered and reported in the literature.
List recently introdice a classification of organicatalyst based on the mechanism of catalysis:
- Lewis based catalyst
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Lewis acid catalyst
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Bronstead base catalyst
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Bronsted acid catalyst
Lewis based catalyst initiates the catalytic cycle by nucleophilic attack on the substrate, and the resulting complex undergoes reaction and releases product and catalyst for the further turn over. Lewis acid catalyst also activate the substrate in a similar manner. Bronsted base and acid catalysis is initiated by the partial protonation and deprotonation, respectively.
Despite the considerable progress that has been made in the elucidation of transition states, we are only beginning to understand the basic factors that control the reactivity and selectivity of these reactions, and the rational design of the catalyst remains in most cases a dream.