Organocatalytic Asymmetric Tandem Michael-Henry Reactions

The strategy of organocatalytic asymmetric domino reactions to construct complex framworks from simple precursors has blossomed so dramatically that the scope of organocatalysis in the field of asymmetric catalysis has been expanded significantly in the past few years. In this dissertation, recent advances in the organocatalytic asymmetric domino reactions were summarized and reviewed according their catalytic mechanism modes firstly, especially in chiral amine catalyzed enantioselective domino reactions. Then, two enantioselective Michael-Henry domino reactions catalyzed by diamine catalysts and amine-thiourea catalysts to afford chiral 3-nitro-2H-chromenes and 3-nitro-l, 2-dihydroquinolins have been studied respectively.An enantioselective oxa-Michael-Henry reaction of substituted salicylaldehydes with nitroolefins that proceeds through an aromatic-iminium-activation (AIA) has been developed by using a chiral diamine organocatalyst and a co-catalyst salicylic acid. The corresponding 3-nitro-2H-chromenes were obtained in moderate-to-good yields with up to 91 % ee under mild conditions. Based on the experimental results and ESI mass spectrometric detection of the intermediates, a plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.In the following study, an enantioselective aza-Micheal-Henry reaction of 2-amino benzaldehydes with nitroolefins synergistically promoted by simple bifunctional amine-thiourea organocatalysts was presented. A variety of substrates could be utilized to give chiral 3-nitro-1, 2-dihydroquinolines with a good enantioselectivity (up to 90% ee). Furthermore, based on the absolute configuration of the products and ESI-MS studies of the intermediates, an interesting reaction model involving both hydrogen-bonding interactions and aromatic iminium amongst the amine-thiourea catalyst and the reactants has been proposed.In conclusion, two kinds of organocatalytic enantioselective Michael-Henry reactions were disclosed to realize the asymmetric synthesis of 3-nitro-2H-chromenes and 3-nitro-1, 2-dihydroquinolins, which are valuable intermediates due to their versatile modifiability. The aromatic iminium activation catalytic mode was firstly proposed and confirmed by experimental results.