The Catalytic Asymmetric Cyclization Reactions Of Azomethine Ylides

To be regarded as an important synthetic intermediate, azomethine ylide was widely used in synthesis of many medical intermediates and natural products. In the past decade, much attention has been paid to the catalytic asymmetric reaction of azomethine ylide, especially for the catalytic asymmetric [3+2] cycloaddition. A great deal of research and good results have been achieved in our research group in recent years. In order to get more kinds of chiral heterocycles using the azomethine ylide or similar synthons, we designed several kinds of catalytic asymmetric cycloaddition based on the structural features of azomethine ylide. My research work mainly contains the following three parts:1) According to the catalytic asymmetric1,3-dipolar [3+2] cycloaddition of azomethine ylides with (Z)-sulfonyl acrylate, we tried to investigate the regioselectivity and enantoselectivity of azomethine ylides with the olefin bearing two different electron-withdrawing groups on ?-and ?-position. Respectively, when AgOAc/(S)-TF-Biphamphos was employed as the chiral catalyst, the ester-directing regiochemical controlled cycloadducts were obtained with high yields (73-98%), high endo/exo-selectivities (>98:2dr) and high enantioselectivities (95-99%ee). Especially for the imino esters bearing substituent groups on a-position, the chiral pyrrolidine derivates with a quaternary carbon center were also obtained with high selectivity. Based on the experimental results and DFT calculation, a plausible transition state model and reaction mechanism was proposed.2) The first catalytic asymmetric1,3-dipolar cross-cycloaddition of azomethine ylides with pyrazolidinium ylides has been successfully developed, which provides an convenient method to construct chiral1,2,4-triazinane framworks. A series of1,2,4-triazinane derivatives bearing a diversity of functional groups were realized with high yields (67-94%), high endo/exo-selectivities (>20:1) and high enantioselec-tivities (74-98%ee) when employing CuBF4/(S,Sp)tBu-Phosferrox as the chiral catalyst. Various kinds of azomethine ylides and pyrazolidinium ylides worked smoothly in this catalytic system.3) An unprecedented catalytic asymmetric inverse-electron-demand aza-Diels-Al-der reaction of indoles with in situ formed azoalkenes has been developed, which provides a convenient method to get chiral pyridazino[3,4-b]indole derivates. Using CuBF4/(S,Sp)-tBu-Phosferrox as the chiral catalyst, desired products have been obtained with high yields(81-97%), high diastereoselectivities (94:6->20:1) and high enantioslectivties (78%-99%ee). And a broad substrate scope was achieved in this catalytic system. A plausible transition state model was proposed according to the experimental results of nonlinear effect.