Synthesis Of Bifunctional L-Prolinamide Derivative Organocatalysts

Since 2000, the early discovery of List and Barbas that L-proline was used as the catalyst for the enantioselective direct aldol reaction, several L-proline derivatives, including L-prolinamide derivatives, have been synthesized and applied for highly enantioselective direct aldol reaction, Michael addition and Mannich reaction. So far, catalyst loading as low as 2mol% and enantioselectivity up to >99% ee were achieved with some of the most recent catalysts. However, even with these great advances, the activity of most organocatalysts was dependent on the substrates. Recently, the development of new organocatalysts by combining a Lewis acid and a Lewis base has focused much attention.In this thesis, L-proline as an ingredient, bifunctional L-prolinamide derivative organocatalysts were synthesized via the esterification reaction, ammonolysis reaction and condensation reaction.(1) The synthesis of L-proline methyl ester : L-proline methyl ester was prepared via the esterification reaction at ambient temperature between L-proline and thionyl chloride in methanol in 83.2% yield.(2) The synthesis of N-(2-aminoethyl)-L-prolinamide: N-(2-aminoethyl)-L- prolinamide was prepared via the ammonolysis reaction at ambient temperature between L-proline methyl ester and excess ethylendiamine in methanol in 80.0% yield.(3) The synthesis of bifunctional L-prolinamide derivative organocatalyst 1: the product 1 was synthesized via the condensation reaction at ambient temperature between salicylaldehyde with N-(2-aminoethyl)-L-prolinamide in CH2Cl2 in 27.5% yield.(4) The synthesis of bifunctional L-prolinamide derivative organocatalyst 2: the product 2 was synthesized via the condensation reaction at ambient temperature between 3,5-di-t-butylsalicylaldehyde with N-(2-aminoethyl)-L-prolinamide in CH2Cl2 yield 31.0%.In addition, an interesting phenomenon was observed in our experiment. Besides the products 1 and 2, we also detected the formation of diheterocyclic compounds, which formed in the condensation reaction between secondary amine in pyrrole ring and salicylaldehyde/3,5-di-t-butylsalicylaldehyde.