Study Of Small Organic Molecular-catalyzed Asymmetric(Aza) Michael Addition Reactions

During the last decade, organocatalysis has been one of the most rapidly growing and competitive fields in asymmetric catalysis, and developed to a third pillar beside metal and biocatalysis, and have an important and far-reaching impact on asymmetric (aza) Michael addition reaction. In this paper, asymmetric (aza) Michael addition reaction as research center, small molecule catalysts and nitrogen nucleophiles as innovation, several efficient organocatalysts and nitrogen nucleophiles have been reported for the first time. Their participation on the asymmetric (aza) Michael addition reactions were studied and good results were obtained.We found that two kinds of C2-symmetric chiral tetraamines derived from L-proline were efficient organocatalysts for the asymmetric Michael reactions for the first time. The tetraamine synthesized from L-proline and o-phenylenediamine has shown to be very effective catalyst for the asymmetric Michael addition reactions of various cyclic ketones and chalcones. The corresponding adducts were obtained in good chemical yields (up to96%) with high levels of diastereo-and enantioselectivities (up to>99:1dr and93%ee) under mild conditions. According to the results of the experiment and studying the ESI-MS of the intermediates, we made a detailed study for the proposed mechanism and determined the control step of the reaction.In addition, the tetraamine synthesized from L-proline and (1R,2R)-1,2-diaminocyclohexane has showed good catalytic activity for asymmetric Michael additions of various cyclic ketones to nitroalkenes as well as chalcones. The situation is rare among reported catalytic systems. The Michael adducts were obtained in excellent yields (84-99%) and good diastereo-and enantioselectivities (up to97:3dr and91%ee) for asymmetric Michael reactions to nitroalkenes, and moderate to high yields (61-91%) with good diastereo-and enantioselectivities (up to>99:1dr and93%ee) for the reactions to chalcones.Nitrogen nucleophiles as innovation, the first application of4-nitrophthlimide as novel and effective nitrogen nucleophile for asymmetric aza-Michael addition to a, β-unsaturated ketones has been developed. Under mild conditions, utilizing9-epi-9-amino-9-deoxyquinine as catalyst, a range of chalcones and aliphatic a, β-unsaturated ketones were examined, affording the corresponding adducts in moderate to high yields (49-98%) with excellent enantioselectivities (95->99%ee). All the products were unreported new compounds, and their structures were determined by1H NMR,13C NMR and HR-MS. Their absolute configuration were determined by diffraction analysis. Computational studies demonstrate the reason of4-nitrophthalimide as a suitable nucleophile may be due to its structural characteristics, making it easier to be activated so that it has stronger nucleophilicity. In addition, we have also made reasonable prediction and discussion about the reaction mechanism.The first enantioselective aza-Michael addition of4-nitrophthalimide to nitroalkenes was reported. It is particularly noteworthy that this new catalytic asymmetric aza-Michael addition is effective for aromatic and aliphatic nitroalkenes, utilizing chiral thiourea catalyst derived from cinchonine as catalyst, the process gave corresponding Michael adducts in moderate yields (up to75%) with up to87%ee. All the products were unreported new compounds, and their structures were determined by1H NMR,13C NMR and HR-MS. According to the characteristics of the substrate and the structure of the catalyst, we have made reasonable prediction and discussion about the possible reaction mechanism. In addition, activity test showed that some products of the reaction have moderate or good herbicidal activity against cole and barnyard grass at100μg/mL.The first asymmetric aza-Michael additions of phthalimide derivatives to a, β-unsaturated aldehydes have been reported. Utilizing diarylprolinol TMS ether as the catalyst, the reactions proceeded smoothly to afford corresponding Michael adducts in high yields (70-98%) with good enantioselectivities (up to95%ee). All the unreported new compounds were determined by1H NMR,13C NMR and HR-MS.