Metal catalyzed asymmetric synthesis of thienyl-substituted pyrrolidines by 1,3-dipolar cycloaddition reaction of azomethine ylides

Bulut, Merve
Pyrrolidines are structurally and biologically important heterocyclic compounds. One of the efficient methods for the synthesis of these compounds is 1,3-dipolar cycloaddition (1,3-DC) reaction of azomethine ylides with electron deficient dipolarophiles. Asymmetric synthesis of these compounds has been studied by many groups by using 1,3-DC reactions with chiral transition metal catalysts. In all these studies aryl-substituted pyrrolidines were synthesized mainly. In this thesis, heteroaryl-substituted pyrrolidines which were not explored in the literature will be synthesized by using chiral metal catalysts developed in our group. Chiral metal catalysts are composed of a metal and a chiral ligand. As the metal source, Cu-, Zn-, and Ag-salts were used with FAM (ferrocenyl aziridinyl methanol) chiral ligands. Besides the known FAM ligands, a new derivative, CFAM (cyclohexyl ferrocenyl aziridinyl methanol), was also synthesized for the first time in this thesis. With the CFAM chiral ligands, total of twelve chiral ligands (PFAM1-4, CFAM1-4, and 1-NFAM1-4) were screened for the synthesis of thienyl-substituted pyrrolidines. After optimizing all the reaction parameters (temperature, concentration, solvent, etc.), Ag-PFAM1 catalyst system found to be the better one by forming thienyl-substituted pyrrolidines in 85% ee and 64% yield with N-methylmaleimide.


Chiral metal catalyzed enantioselective synthesis of pyridinyl pyrrolidine derivatives
Gözükara, Zeynep; Doğan, Özdemir; Department of Chemistry (2019)
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 chir...
Synthesis of 6-halogen-substituted 2-methylene-2,3dihydro-1,4-oxazepine derivatives
İbiş, Özge; Zora, Metin; Department of Chemistry (2017)
Heterocyclic compounds are important since they are present in life naturally or synthetically. Among heterocyclic compounds, seven-membered 1,4-oxazepines are giving more attention than ever due to their wide range of biological and medicinal activities. There are many studies about their synthesis and new ones continue to appear. In this study, synthesis of halogen-substituted 1,4-oxazepine derivatives was investigated, which may have potential for biological studies. For this purpose, α,β-alkynic ketone ...
Stereoselective oxidation of sulfides to sulfoxides by n-chloramines
İpek, Halil; Akdağ, Akın; Department of Chemistry (2014)
Chiral sulfoxides are present in many biologically active compounds. Asymmetric synthesis of the sulfoxides has been performed by chiral metal complexes and chiral peroxides. Although the asymmetric organooxidation of sulfides by chiral peroxides proved to be successful, peroxides are difficult to handle and obtain. In this study, a new metal free method has been developed to oxidize sulfides to chiral sulfoxides with easily accessible chiral N-chloramines. For this purpose, chiral reagents were synthesized...
Synthesis of ferrocenyl substituted pyrazoles by sonogashira and suzuki-miyaura cross-coupling reactions
Karabıyıkoğlu, Sedef; Zora, Metin; Department of Chemistry (2010)
Pyrazoles constitute one of the most important classes of heterocyclic compounds due to their interesting chemical and biochemical features. Researchers have studied many pyrazole containing structures for almost over a century in order to investigate the various biological activities possessed by these molecules. A new and important trend in these studies is to produce ferrocenyl substituted pyrazoles since ferrocene attracts considerable interest in the research field of organometallic and bioorganometall...
Beksultanova, Nurzhan; Doğan, Özdemir; Department of Chemistry (2021-7-16)
Aziridines are small three-membered heterocyclic compounds. They are important as building blocks for many nitrogen-containing biologically active compounds and as chiral ligands in metal catalyzed asymmetric synthesis of different organic compounds. In the first part of this thesis, we have studied the ring opening reactions of various racemic and chiral aziridine-2-phosphonates. Regioselective aziridine ring opening reaction with HCl formed -amino--chlorophosphonates in 60-95 % yield and the same reacti...
Citation Formats
M. Bulut, “Metal catalyzed asymmetric synthesis of thienyl-substituted pyrrolidines by 1,3-dipolar cycloaddition reaction of azomethine ylides,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Chemistry., Middle East Technical University, 2019.