Synthesis And Immobilization Of Proline Dipeptides Organocatalyst

Organocatalysts have widely applications in the field of asymmetric synthesis, especially, enantioselective C-C bond forming reactions,such as aldol reaction, Michael reaction, etc. Recently, many researchers have focused on the design and synthesis of new and highly efficient organocatalystsIn this paper, we incorporated both prolinamide moieties and aminopyridine in one molecule could give the potential organocatalysts.Boc-1～Boc-9 (65%～92%,yield )were synthetized by mixed anhydride method or DCC condensation using N-Boc-L- proline N-Boc-4-OH-L-proline and Picolinamide respectively, Finally, the catalysts 1-9 were synthesized after being deprotected by TFA.The aldol reaction is one of the most important organic reactions, because it is a carbon-carbon bond forming reaction which produces highly functionalized compounds with a pair of newly generated chiral centers. We first examined the ability of the catalysts 1-9 to promote the direct aldol reaction between cyclohexanone and 4-nitrobenzaldehyde under various conditions. Catalysts 1, 4 and 9 are identified as the best catalysts for this reaction which lead to aldol adduct with excellent enantioselectivity and ee value up to 96%, dr value upto >99:1.The reactions of different aromatic aldehydes with cyclohexanone were studied under the optimized conditions (using 20 mol% of 1 as catalyst in CHCl3). The reactions of different aromatic aldehydes, which bear an electron-withdrawing group on the benzene ring, proceeded smoothly in excellent enantioselectivities (ee 94%, dr> 99:1) to furnish the aldol adducts. In addition, halogenated benzaldehydes led to decreased yields. Interestingly, the ee values of the products remained at good levels. On the other hand, this catalytic system was proven to be completely ineffective for the aromatic aldehydes with an electron-donating group or without any substitution.The Michael reaction is also an important C-C bond forming reaction in organic synthesis. We investigated the application of catalysts 1, 4and 9 for the Michael reaction between cyclohexanone and trans-β-nitrostyrene under the optimized reaction conditions. In the presence of 10 mol% catalyst loading, catalysts 1, 4 and 9 gave the product of cyclohexanone reacting with trans-β-nitrostyrene in moderate yield (up to 91% yield) and high diastereoselectivity( dr up to 99:1), but poor poor to moderate enantioselectivity( up to 70%, ee).The catalyst 1 was supported using Mesoporous-silica. We first examined the ability of the catalyst to promote the direct aldol reaction between acetone and 4-nitrobenzaldehyde under various conditions. Resultly, The catalyst had moderater catalytic activity ( ee 76, dr 90:10). The supported catalyst could be easily separated from the reaction system by filtration and reused at least six times without significant lost of activity and enantioselectivity.Via the researching work of this dissertation, suggest a new strategy in the design of new organocatalystss for direct asymmetric aldol reactions and related reactions and make the design and synthesis of catalyst possible to multiple reactions. While, our work provide experience for silica supported organocatalyst.