Design And Synthesis Of Enamine-type Prolinamide Organocatalysts Based On Molecular Recognition And Their Applications In Asymmetric Michael Addition

Objective:Organocatalysis is an important mechanism of asymmetric synthesis. Design and synthesis organocatalysts that is consistent with atom economy strategy have become the hot topic in asymmetric catalysis. In this paper, the novel pyrimidinyl and N-nitrophenyl prolinamide organocatalyst based on molecular recognition and enamine catalysis were synthesized. The applications of the above organocatalyst in asymmetric Michael addition was investigated. The organocatalysts is expected to give excellent catalytic efficiency and stereo selectivity. Methods:1.N-Cbz-L-proline and 2- amino- pyridine compounds or nitro- aniline compounds were used as starting materials, undergoing amidation coupling reactions and removal of Cbz protecting group which then giving novel prolinamide organocatalysts; 2.The organocatalysts were applied in asymmetric Michael addition. According to the yield of the addition product,enantioselectivities and diastereoselectivities, the catalytic efficiency and the stereo selectivity of the organocatalysts were evaluated. Results:1.Five prolinamide organocatalysts were designed and synthesized, their structures were confirmed by ESI-MS, 1HNMR, 13 CNMR, HR-MS and IR spectra, and all of them have not been reported in the literature; 2.The organocatalysts were applied in asymmetric Michael addition of cyclohexanone to Chalcone, but affordedthe poor yield of adducts. While, the organocatalysts could catalyzed the asymmetric Michael addition of cyclohexanone to nitroalkene to give the desired adducts with excellent yield(93%), diastereoselectivities(up to 99:1 dr) and moderate enantioselectivities(45% ee) under mild conditions. The enantioselectivity observed is unusual. Conclusion:1.Five novel prolinamide organocatalysts were obtained, all of them have not been reported in the literature, And the synthetic route of the organocatalysts was established; 2.The organocatalysts were applied in asymmetric Michael addition of cyclohexanone to nitroalkene to give the desired adducts with excellent yield(93%), diastereoselectivities(up to 99:1 dr) and moderate enantioselectivities(45% ee) under mild conditions. The catalytic activity of the organocatalysts is good, but the stereo selectivity is moderate.