Stereoselective construction of 2-oxindole fused spirocycle precursors /

Download

index.pdf

Date

2019

Author

Karahan, Seda

Metadata

Show full item record

Item Usage Stats

257
views

141
downloads

Recent literature on the bioactivity of isatin (indoline-2,3-dione) derivatives triggered organic chemists to make use of the unique potential of isatin in asymmetric organocatalytic synthesis. Due to extensive presence of 2-oxindole skeleton, especially spiro-fused cycles, in many natural products, they drew the special interest in the disciplines of medicinal chemistry and agrochemistry. Due to highly reactive prochiral carbonyl group, isatins are potent precursors for the synthesis of 3,3-disubstituted spirooxindoles. Direct nucleophilic addition to isatin-derived ketimines is one of the straightforward approaches leading to α-chiral amines which are frequent subunits of pharmaceuticals and agrochemicals besides being heterocycle precursors. In this respect, asymmetric organocatalytic synthesis offers facile and environmentally benign reaction process and selectivity as well. Remarkable advantages of cooperative activation of substrates via bifunctional organocatalysts bearing H-bond donor components such as urea, thiourea and squaramide are indispensable. Modulation of sterically encumbered units such as 1-adamantyl, 2-adamantyl and t-butyl in the structure of organocatalyst reveals distinct changes in stereoselectivity of the synthetic transformations. In this thesis study, we aimed to utilize new quinine-based squaramides in the asymmetric aza-Friedel-Crafts and Mannich reactions of isatin ketimines to obtain corresponding chiral 2-oxindoles with 1,3-aminonaphthol and 2-azidoethanamine functionalities, respectively. A new quinine-derived squaramide organocatalyst revealed excellent stereoselectivity up to >99% ee in aza-Friedel-Crafts reaction also up to 96% ee and 24:1 diastereomeric ratio in Mannich reaction of N-carbamate protected isatin ketimines. Additionally, representative examples of 1,4-naphthoxazepines, 1,2,3-triazoles and cyclic ureas were synthesized to demonstrate the synthetic potential of these novel chiral 3,3-disubstituted 2-oxindoles as being heterocycle precursors. Reaction scope, limitations and activation modes of organocatalysts were discussed in detail.

Subject Keywords

Isatin., Catalysis., Asymmetric synthesis., Organic compounds

URI

http://etd.lib.metu.edu.tr/upload/12622962/index.pdf
https://hdl.handle.net/11511/27910

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Asymmetric diethylzinc addition to N-sulphonyl and N-phosphinoyl arylaldimines Çağlı, Eda; Doğan, Özdemir; Department of Chemistry (2013) Design of new chiral ligands for asymmetric synthesis is important. The ligand should be economical and efficient in enantioselective transformations. For the synthesis of some natural products and biologically active compounds, optically active amines are used as important intermediates. For this reason, it is significant to develop new catalyst system which can produce optically active amines in an economical and efficient way. Our group developed PFAM ligands and used successfully for the enantioselectiv...
Synthesis of chiral lactones via the baeyer villiger oxidation of cyclic aromatic acetoxy ketones novel annulation reactions of 2-propynyl-1,3-dicarbonyl compounds to form pyrroles addition of acyl phosphonates to diethyl cyanophosphonate (depc) Aybey, Asuman; Demir, Ayhan Sıtkı; Department of Chemistry (2009) Chiral Baeyer-Villiger (BV) oxidation of cyclic ketones allows rapid access to asymmetric lactones as valuable intermediates in organic chemistry and frequently encountered precursors in enantioselective synthesis. In the first part, BV oxidation of functionalized ketones, especially cyclic -hydroxy and acetoxy ketones is described which could be a straightforward route to the -hydroxy lactones and -hydroxyalkanoic acid derivatives. The -acetoxylation of indanone, tetralone and chromanone derivatives by usi...
Bifunctional 2-aminodmap/thiourea catalyzed enantioselective michael addition of thioacetic acid to trans-beta-nitrostyrenes Kabasakal, Zehra; Tanyeli, Cihangir; Department of Chemistry (2013) Michael addition reactions as an efficient method for carbon-carbon bond formations have been intensively explored in the context of enantioselective organocatalysis using aldehydes, ketones, 1,3- dicarbonyl compounds and nitroalkenes as donors. However, there are very few studies using thiol derivative as a nucleophile. In this thesis, enantioselective Michael addition reaction of thioacetic acid as Michael donor and 10 trans-β-nitrostyrene derivatives as Michael acceptors have been studied. The products o...
Chemoenzymatic synthesis of chiral hydroxymethyl cycloalkenols Şenocak, Deniz; Demir, Ayhan Sıtkı; Department of Chemistry (2004) Chiral cyclic alkenols with hydroxymethyl functionality are important structural units in many biologically active natural compouds such as prostaglandins, sesquiterpene antiviral agents, pentenomycins, xanthocidin, sarkomycin, etc. 1,3-cycloalkanediones are converted into bicyclic polyoxo derivatives with formaldehyde and trioxane in the presence of Lewis acid. Selective oxidation of the bicyclic compounds by using manganese(III)acetate followed by enzyme-catalyzed kinetic resolution afforded chiral bicycl...
Stereoselective Synthesis of 1,2,3-Triazolooxazine and Fused 1,2,3-Triazolo-delta-Lactone Derivatives Gümüş, Ayşegül; Mert, Kudret; Tanyeli, Cihangir (2014-10-01) The stereoselective synthesis of 1,2,3-triazolooxazine and fused 1,2,3-triazolo--lactone by applying chemoenzymatic methods is described. trans-2-Azidocyclohexanol was successfully resolved by Novozyme 435 with an ee value of 99%. Installation of the alkyne moiety on the enantiomerically enriched azidoalcohol by O-alkylation, followed by intramolecular azidealkyne [3+2] cycloaddition resulted in the desired 1,2,3-triazolooxazine derivative. Enantiomerically pure azidocyclohexanol was also subjected to the H...

Citation Formats

S. Karahan, “Stereoselective construction of 2-oxindole fused spirocycle precursors /,” Ph.D. - Doctoral Program, Middle East Technical University, 2019.