Asymmetric Catalytic Synthesis Of Spiro "Nitrogencycle-3, 3'-oxind Ole" Unit

The chiral spiro[nitrogencycle-3,3'-oxindole] unit constitutes a core structural element prevalent in a large family of natural products or biological active molecules On one hand, the unique structure of these natural compounds has attracted much attention from synthetic chemists; on the other hand, the significant biological activity has intrigued intense interest in the development of biologically promising analogues with improved efficiency and selectivity. Catalytic asymmetric methods to access these compounds would be highly valuable. In this manuscript, we have developed two new approaches for catalytic asymmetric synthesis of optically active derivatives containing the spiro[nitrogencycle-3,3'-oxindole] unit, respectively.The asymmetric 1, 3-dipolar cycloaddition of azomethine ylides to alkene represents an efficient and atom-economic method for enantioselective synthesis of pyrrolidine derivatives. However, methyl 2-(2-nitrophenyl)acrylate and its analogues were seldom successfully involved in highly enantioselective catalytic variants. In this manuscript, we have described a chiral Br?nsted acid-catalyzed 1,3-dipolar cycloaddition reaction of methyl 2-(2-nitrophenyl)acrylate with azomethine ylides, yielding highly enantioenriched pyrrolidine derivatives, which can be readily transformed to spiro[pyrrolidin-3,3'-oxindole] unit by easily operative reactions. The methodology holds great potential in total synthesis as demonstrated by its applications to the synthesis of diastereoisomers of spirotryprostatin A. The biological evaluation suggested that the configuration of the stereogenic center of spirooxindole (C9 and C18) was not the key element affecting the anti-cancer biological activity of spirotryprostatin alkaloids.The concept of combining transition metal catalysis and organocatalysis has emerged as a promising strategy for developing new and valuable reactions, and has attracted considerable attention as it hold great potential in the creation of new transformations, which each type of catalysts failed to afford alone. The strategy also provides a powerful tool for saving both energy and resources. In this manuscript, we have presented a highly enantioselective synthesis of spiro[4H-pyrilindin-3,3'-oxindole] derivatives via Mannich reaction of 3-substituted oxindoles and N-Boc-imines followed by intramolecular hydroamination catalyzed by a gold(I) complex with the assistance of a Br?nsted acid additive in one pot. Through systemic study, we found that the combined catalysts with a chiral 1,2- diphenylethylene-diamine skeleton 5.5e and PPh3AuNTf2 were the best catalysts of the reaction. Under the optimized reaction conditions, middle yield and excellent levels of enantioselectivity could be obtained.