Design and Synthesis of L-Proline Derivatives as Enantioselective Organocatalysts for Synthesis of the (S)-Wieland-Miescher Ketone

Some simple L-proline derivatives were designed as the organocatalysts for asymmetric synthesis of (S)-Wieland-Miescher Ketone. Their catalytic efficiencies were predicted based on DFT (Density Functional Theory) calculations. The results of DFT calculations were in good agreement with that of experiment. In order to further investigate the effects of substituent groups attached to CONH on catalytic efficiencies, 12 other L-proline derivatives were designed, synthesized and tested the catalytic efficiencies. Some of title organcatalysts (C04 and D01) exhibited excellent catalytic efficiencies (up to 93% ee and 88% yield) with a very low loading (0.5-1mol%) under solvent-free conditions. Meanwhile, microwave irradiation was used for accelerating the reaction, and the reaction time had been decreased to 3 hours. Organocatalysts D01 derived from cheap isopropylamine would make the preparation of (S)-Wieland-Miescher Ketone a lot easier and cheaper.