Chiral metal catalyzed enantioselective synthesis of pyridinyl pyrrolidine derivatives

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2019
Gözükara, Zeynep
Pyrrolidine skeleton can be found as core structures in many natural compounds. Almost all pyrrolidine derivatives show some biological activities and some of them are used as drugs. These compounds can be synthesized by 1,3-dipolar cycloaddition reaction of azomethine ylides with dipolarophiles. This strategy is one of the most efficient and atom economical reaction, because two “C-C” bonds and up to four stereogenic centers can be created in a single step. Our group has synthesized amino alcohol type chiral ligands having ferrocene and aziridine units in their structures. These ligands are shortly called FAM and used with a metal as chiral catalyst for the enantioselective synthesis of organic compounds. In this thesis these chiral catalysts and new derivatives (1-NFAM and CFAM) were screened for the first time in the literature for the enantioselective synthesis of pyridinyl substituted pyrrolidine derivatives. For the synthesis of pyrrolidine structures, 1,3-dipolar cycloaddition of azomethine ylides with electron deficient dipolarophiles were used. Imines, the precursors of azomethine ylides, were prepared by condensation of 2-, 3-, and 4- pyridinecarboxaldehyde with glycine methyl ester. Dimethyl maleate, tertiarybutyl acrylate, methyl acrylate, N-methylmaleimide, trans-chalcone, and vinylsulfone were used as the dipolarophiles. As the metal sources, silver, copper and zinc salts were tested. After optimizing the reaction conditions by changing many parameters, it was found that PFAM1 chiral ligand with silver is catalyzing the reaction better than the other ligands and metal sources by forming the product in 94% yield and 48% ee.

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Citation Formats
Z. Gözükara, “Chiral metal catalyzed enantioselective synthesis of pyridinyl pyrrolidine derivatives,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Chemistry., Middle East Technical University, 2019.