One-pot synthesis of chloroalcohols and their lipase mediated kinetic resolution - ferrocenyl aziridinylmethanols as chiral ligands in enantioselective conjugate diethylzinc addition to enones

Download

index.pdf

Date

2007

Author

İşleyen, Alper

Metadata

Show full item record

Item Usage Stats

129
views

157
downloads

An unexpected tricyclic ether formation instead of acetate addition to the double bond of a norbornene derivative aroused our interest to explore the mechanism of this reaction. Mechanistic studies showed that methylene diacetate (MDA) was formed in the stock solution (NBu4OAc + dichloromethane) and decomposed to formaldehyde under Lewis or Brønsted acid conditions. Formaldehyde and olefin condensation (Prins reaction) clearly explains the formation of the unexpected product. Same methodology was then successfully applied to develop a one-step procedure for the synthesis of 3-chloro-3-arylpropanols, which are important starting materials for the synthesis of biologically active benzanilide derivatives. Styrenes were reacted with MDA in the presence of boron trifluoride to give the corresponding 3-chloro-3-arylpropanols in 3684% yield. The second part of the thesis involves kinetic resolution of 3-chloro-3-arylpropanols by lipase mediated acylation which are described for the first time. Acylation with the CCL provided the best enantioselectivity amongst the enzymes used. Enantiomerically enriched products with up to 78% ee were obtained after two successive lipase-mediated acylations. Different substituents on the aromatic ring and bromide, instead of chloride, at the benzylic position of the substrates were found to have no drastic influence on the enantioselectivity of the reaction. In the last part, easily available ferrocenyl substituted aziridinylmethanols (FAM) were complexed with nickel to catalyze the enantioselective diethylzinc addition to various enones with ee’s reaching 82%. The ligands can be recovered and used without losing their activity. The sense of asymmetric induction was found to be dependent on the configuration of the aziridine ring.

Subject Keywords

Chemistry, Organic

URI

http://etd.lib.metu.edu.tr/upload/12608857/index.pdf
https://hdl.handle.net/11511/17212

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

One-Pot Synthesis of Spiro-2H-pyrroles fromN-Propargylic beta-Enaminones KARADENİZ, EDA; Zora, Metin (Georg Thieme Verlag KG, 2019-06-01) A simple and general one-pot method for the synthesis of spiro-2 H -pyrroles has been developed. Initially, cyclohexane-embedded -enaminones with internal alkyne functionality were synthesized by conjugate addition of 1-ethynylcyclohexylamine to ,-alkynic ketones, followed by palladium-catalyzed coupling of the resulting N -propargylic -enaminones with aryl iodides. When subjected to basic conditions, the cyclohexane-embedded -enaminones with internal alkyne functionality underwent tandem nucleophilic cycli...
A facile synthesis of various butenolides Tanyeli, Cihangir (Informa UK Limited, 2000-01-01) The synthesis of alpha'-acyloxy-alpha,beta-unsaturated cyclic ketones from the corresponding alpha,beta-unsaturated cyclic ketones by using manganese (III) acetate in combination with 2-chloropropionic acid followed by subsequent Arbuzov and intramolecular Horner-Emmons cyclization reactions provided a convenient synthetic pathway to various butenolides 4a-d.
The effect of the double bond pyramidalization on the mode of the bromination reaction: Bromination of benzobicyclononadiene Balcı, Metin; Guney, Murat; Dastan, Arif; Azizoglu, Akin (American Chemical Society (ACS), 2007-06-22) The bromination of 6,7,8,9-tetrahydro-5H-5,9-ethenobenzo[a][7]annulene yielded regio- and stereospecifically formed dibromides arising from the alkyl shift where the bromine exclusively attacks the double bond from the endo face of the double bond. DFT calculations on model compounds showed that the pyramidalization of the double bond and steric repulsion caused by the methylene protons are responsible for the stereo- and regioselective addition of bromine.
Synthesis of 1,2,3,5- tetrasubstituted pyrrole derivatives via 5-exo-dig type cyclization and stereoselective functionalisation of ferrocene derivatives Kayalar, Metin; Demir, Ayhan Sıtkı; Department of Chemistry (2005) A convenient and new method for the synthesis of 1,2,3,5-tetrasubstituted pyrrole derivatives starting from 1,3,-dicarbonyl compounds through acid catalyzed cyclization reaction is described. Alkylation of 1,3-dicarbonyl compound with propargyl bromide followed by one step cyclization with the introduction of primary amines in the presence of catalytic amount of triflouroacetic acid (TFA) affords the corresponding pyrrole derivatives in high yields. The investigations on the studies of developing a new meth...
Unusual fragmentation of fulvene endoperoxides with phenyliodosyl bis(trifluoroacetate) (PIFA) Ozer, G; Saracoglu, N; Balcı, Metin (Wiley, 2003-05-01) Reaction of unsaturated fulvene endoperoxides with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate gave saturated fulvene endoperoxides containing the 1,2-dihydropyridazine ring. Treatment of dihydropyridazine endoperoxides with water followed by phenyliodosyl bis(trifluoroacetate) oxidation provided acrylic acid derivatives and dimethyl pyridazine-3,6-dicarboxylate.

Citation Formats

A. İşleyen, “One-pot synthesis of chloroalcohols and their lipase mediated kinetic resolution - ferrocenyl aziridinylmethanols as chiral ligands in enantioselective conjugate diethylzinc addition to enones,” Ph.D. - Doctoral Program, Middle East Technical University, 2007.