Asymmetric Michael Addition Of Nitroalkanes To 2-Enoyl- Pyridine N-Oxides

The Michael addition has emerged as a powerful tool in organic synthesis for constructing carbon-carbon bonds. Although impressive progress in the transition-metal-catalyzed asymmetric Michael additions has been made in the past decades, there remains a great challenge in the diastereoselectivity issue of Michael additions. It is noteworthy that a satisfactory diastereoselectivity in the Michael addition of nitroalkanes to α,β-unsaturated ketones still is a challenging problem despite the immense developments in the enantioselective version of this reaction. Meanwhile,2-enoyl-pyridine N-oxide as a popular Michael acceptor has been extensively explored in the asymmetric transformations. In this context, the asymmetric Michael addition of nitroalkanes with 2-enoyl-pyridine N-oxide was chose as a model reaction to address the issue of diastereoselectivity.This thesis includes four parts. The first part summarizes the Michael addition of nitroalkanes and the asymmetric reaction involving 2-acyl-pyridine N-oxides. The second and third parts show the enantioselective and diastereoselective addition of nitroalkane to 2-enoyl-pyridine N-oxides. The fourth part is the experiment part.Two transition-metal catalysts, chiral scandium(III) and copper(II) complexes, have been developed to achieve a high enantioselectivity in the Michael addition of nitromethane to 2-enoyl-pyridine N-oxides. More importantly, a switchable enantioselectivity was realized by virtue of these two types catalysts. Remarkably, the chiral scandium(III) catalyst showed great activity in the Michael reaction employing other nitroalkanes, such as, nitroethane and nitropropane. With this efficient catalyst, not only a high enantioselectivity but also an unprecedented diastereoselectivity was achieved. Moreover, a relatively rare negative nonlinear effect was observed in this process. On the basis of this finding, the control experiments and the NMR monitoring study, the corresponding transition state model involved in this reaction was proposed.