We synthesized alkylated tetramic acid derivatives and optimized the reaction conditions for the optimal enantioselectivity of the model reaction. We started the synthetic pathway with the transformation of Boc-protected glycine (1) and Meldrum's acid into tetramic acid 2. It was followed by Michael addition of trans-β-nitrostyrene in the presence of achiral organic catalyst, resulting in the formation of tert-butyl 4hydroxy-3-(1-phenyl-2-nitroethyl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate (3). In the next step, we alkylated the hydroxyl group of compound 3 with various alkylating reagents RX and thus prepared a group of O-alkylated derivatives 4. Then we performed a stereoselective synthesis of a selected derivative 4.5 with various chiral organic catalysts. We repeated the synthesis in the presence of the optimal organocatalyst in various organic solvents, resulting in optimized reaction conditions. In the last step, we peformed a reaction with substituted derivatives of trans-β-nitrostyrene in the presence of achiral organocatalyst under optimized reaction conditions.
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