Investigation of the efficiency of asymmetric organocatalysts on various organic reactions

The creation of functionalized optically active molecules with structural diversity is related to capability of managing the three-dimensional structure belongs to molecular framework. At this point, asymmetric transformations furnish various ways of generating enantiomerically enriched and enantiomerically pure compounds which are widely utilized in drug discovery and chemical synthesis. Applying catalytic methods that encapsulate enzymatic, metal-catalyzed and organocatalysis are considered as attractive strategies on providing chiral products with high selectivity and atom efficiency. Until the end of the last century, using metal and biocatalysts has predominated, recently organocatalysts which are feasible and effficient tools in comparision with these kinds of catalysts emerged a shift in synthetic perspective. Organocatalysts are metal-free, small organic molecules that have several superiorities over enzymes and metal-catalysts from environmental and economical point of view. They do not entail demanding reaction conditions like inert gas atmosphere and anhydrous solvent due to the insensibility to oxygen and moisture. In addition, they are inexpensive, readily available, recoverable and non-toxic compounds. Owing to the aforementioned advantages, enantioselective organocatalytic processes such as carbon-carbon bond formation reactions has made important progress in recent years. The aldol reaction, that provides an atom-economic approach to β-hydroxy carbonyls is one of the most important carbon-carbon bond forming reactions in modern organic synthesis, as a key step for the synthesis of natural products and biologically active substances. This useful transformation facilitates the construction of larger complex molecules with new stereogenic centers from smaller ones. Subsequent to the using of proline as a catalyst in the intermolecular aldol reaction, prolinamides that eleminates some drawbacks (solubility problems, excessive using, moderate enantioselectivities etc.) of proline have been frequently used in the asymmetric aldol reaction on account of the ability to act as hydrogen bond donors. Thus, the researches on the asymmetric aldol reactions are focused on the design of new catalysts which display high activity and selectivity. The idea behind our research is designing novel chiral organocatalysts with structural diverstiy to catalyze asymmetric direct aldol reaction in various conditions. By this aim, (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid ((S)-THIQA) and L-Proline based new chiral organocatalysts having mono- and dipeptide structure were sythesized. The structure of these catalysts were determined by the FTIR, 1H NMR, 13C NMR, LC-MS and GC-MS spectral data. In the last step, catalytic effect of the synthesized organocatalysts in the enantioselective aldol reaction was investigated. Especially, the good results obtained from (S)-THIQA-based organocatalysts which have not been investigated widely in this field contributed to the literature.