Design of new asymmetric organocatalysts and their application in organic reactions

Developing of new methods for producing optically active substances in the synthesis of single enantiomer of the drug is particularly vital importance. Asymmetric catalytic methods offers a good solution for the separation of racemic mixtures in the chemical industry. But in recent years, small organic molecules are new catalysts which provide high efficiency in enantioselective reactions. Organocatalysts recently has emerged as a new complementary tool to asymmetric organometallic and enzymatic reactions for the synthesis of new materials and enantiomerically rich molecules. There are a number of advantages of organocatalysts over transition metal catalysts and enzyme catalysts. Generally, they are stable, inexpensive, easily obtainable and non-toxic. They do not require harsh conditions such as inert atmosphere and non-aqueous solvents due to their stability. In addition, asymmetric organocatalysts complete the reaction more efficently and they attract attention due to their operational simplicity compared to conventional metal catalysts. Indeed, metal is not used in the most of the biocatalytic process in nature. In this sense, the scientific community are continuing to construct a new field of enantioselective synthesis for metal-free synthetic designs. The greatest interest focuses on the development of the new systems containing proline to use for the asymmetric formation of the C-C bond through enamine as in the aldol condensation. Most important features of these small, inexpensive and natural amino acids are that both of its the two enantiomeric forms can be avaiable and it allows the synthesis of unlimited chiral compounds. However, although proline successfully provides numerous asymmetric transformation, it comprises some disadvantages; difficulty in application (low solubility in organic solvent), non satisfactory catalytic activities, the formation of various side products and lower the reaction rate limit the extent use of these molecules. To overcome these obstacles, modifying proline skeleton which can exhibit high reactivity and selectivity is of great importance. Our research is based on the idea to design new chiral organocatalyst with structural diversity to catalyze asymmetric direct aldol reaction under various reaction conditions. By this aim, synthesis of the L-Proline based new chiral organocatalysts having dipeptide structure have been accomplished. The structure of these catalysts have been determined by the FTIR, 1H NMR, 13C NMR and LC-MS (Q-TOF) spectral data. In the last step, catalytic activity of the synthesized organocatalysts in the enantioselective aldol reaction was investigated. Good yields and enantioselectivities have been observed with newly synthesized L-Proline based organocatalysts.