Organocatalytic resolution of racemic alpha azido ketones

Canbolat, Eylem
Chiral cyclic alpha azido ketones are very important compounds in organic chemistry. Because, the reduced forms of them are amino alcohols and these amino alcohols are interesting compounds for their biological activities. They have some pharmaceutical activities such as: potassium channel open up properties, treatment of central nervous system, antihypertensive properties, the agent of dopamin receptor activator, hypolipemic agent and dopamine agonist. These types of compounds have highly acidic alpha-protons, and many kinds of reactions can be performed with them. In this study, mainly, selective protonation of racemic compounds was performed with a new practical method and there are not so many examples related to deracemization in the literature. Alpha-azido derivatives of tetralone, indanone, chromanone, and thiochromanone structures are chosen as starting materials because of their importance for biological activities arising from their cyclic structures. Firstly, these α-azido compounds were synthesized according to literature. The acidic alpha-protons do not require strong bases. Their enantioselective deracemization and deracemization processes were screened by using Cinchona derivatives as organocatalysts. This screening process was monitored by chiral HPLC columns. The parameters such as catalyst loading, solvent, temperature, reaction time and additives were optimized to obtain high enantioselectivities up to 98%. In addition to deracemization reactions, Michael addition reactions were also performed by starting from α-azido chromanones. In these reactions different type of urea catalyst was used to activate the electrophilic part of trans-β-nitrostyrene compound. Again by controlling the temperature, time and catalyst loading, two diastereomers were formed and the screening process was monitored by chiral HPLC columns again. The Michael products were obtained in up to 94% ee and 75% yield.


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Gadzhili, RA; Nadzhafova, RA; Sesenoglu, O (2002-01-01)
The condensation reaction of 2,3-dichloropropyl- and 2-methoxy-3-chloropropyl alkyl ketones with alkyl 2-aminoacetate salts leads to 1-alkoxy-carbonylmethyl-2-alkylpyrroles. These compounds, with various bases, gave 1-carbamoylmethyl-, 1-dialkylaminocarbonylmethyl-, 1-carbazoyl methyl-2-alkylpyrroles and potassium salt of 2-alkyl-pyrrolyl-1-acetic acid.
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Vatansever, Erol Can; Balcı, Metin; Department of Chemistry (2013)
Synthesis of thiophene containing compounds are of particular interest in synthetic organic chemistry. Besides the importance for synthetic organic chemistry, thiophene derivatives are used in applied research such as drug synthesis and study of functional materials. In this thesis, a new methodology for developing of 2,3-disubstituted thiophenes was developed. This methodology utilizes readily available compounds in a two-step synthesis to provide a facile access to the 2,3-disubstituted thiophenes. In the...
Synthesis of n-(2-propylphenyl) substituted chiral amino alcohols and their usage in enantioselective diethylzinc addition reactions
Günler, Zeynep İnci; Tanyeli, Cihangir; Department of Chemistry (2011)
IChiral 1,2-amino alcohols were synthesized via newly developed “intramolecular unsaturation transfer” using cyclohexanone, propargyl bromide, and various chiral amino alcohols as starting components. These amino alcohols can be potential chiral ligands for many asymmetric transformation reactions. Therefore, their effectiveness as chiral ligands in diethylzinc addition to benzaldehyde and N-diphenylphosphinoyl imines were tested. Various parameters including temperature, solvent, ligand amount etc. were sc...
Synthesis of chiral aziridinyl phosphonates, their biological activities and organocatalytic effect of their phosphonic acid derivatives
Beksultanova, Nurzhan; Doğan, Özdemir; Department of Chemistry (2017)
Aziridines are important three-membered heterocyclic ring systems in synthetic organic chemistry and medicinal chemistry. They can be used as the building blocks for the synthesis of amino acids, amino alcohols, pyrrolidines, pyrroles, lactams, and oxazoles. Aziridinyl phosphonates are attracting more attention in recent years. They are the precursors of α-amino phosphonates that find applications such as enzyme inhibitors and antibacterial agents. One of the methods for the synthesis of these compounds is ...
Organocatalytic enantioselective construction of isatin-derived N-alkoxycarbonyl 1,3-aminonaphthols via sterically encumbered hydrocarbon-substituted quinine-based squaramide
Karahan, SEDA; Tanyeli, Cihangir (2017-09-07)
Herein, an illustrative example to synthesize chiral naphthoxazepine precursors via the aza-Friedel-Crafts reaction of N-alkoxycarbonyl isatin ketimines with naphthol using a new 2-adamantyl-substituted quinine-derived squaramide catalyst is presented; the reaction afforded the chiral-tetrasubstituted 3-amino-2-oxindoles with excellent enantioselectivity of greater than 99% ee and quantitative yields. To the best of our knowledge, this methodology is featured for being representative of the efficiency of st...
Citation Formats
E. Canbolat, “Organocatalytic resolution of racemic alpha azido ketones,” M.S. - Master of Science, Middle East Technical University, 2012.