Novel annulation reactions for the synthesis of substituted pyrroles darzens reaction of acyl phosphonates with α-bromo ketones : selective synthesis of cis- and transepoxyphosphonates

Emrullah, Mustafa
In the first part of this thesis, it is aimed to develope methods for the synthesis of trisubstituted pyrrrole derivatives. 2-Aminopyrrroles, alkoxy and sulfonyl substittitued pyrrole derivatives as well as pirolinones show interesting biological activities and are precursor of well know drugs. Although there is a number of methods for the synthesis of pyrroles, the synthesis of 2-aminopyrroles is limited to few works and is not widely known. Therefore, it is still an important goal in organic chemistry to improve methods for the synthesis of multifunctionalized pyrrole derivatives and pyrrolinones. Alkylation of β-dicarbonyl compounds with bromoacetonitrile furnishes α- cyanomethyl-β-dicarbonyl compounds. The condensation reaction of α- v cyanomethyl-β-dicarbonyl compounds with amines catalyzed by p-TsOH affords the corresponding enamines and further base catalyzed cyclization furnishes 2- aminopyrroles in high yields, moreover, zinc perchlorate-catalyzed addition of amines, alcohols and thiols to the nitrile carbon of α-cyanomethyl-β-ketoesters followed by annulation gives the 5-alkoxy and 5-alkylsulfanylpyrrole-3-carboxylates in high yields. In the second part of the thesis, reactions of a broad range of acyl phosphonates with α-bromo acetophenones at room temperature in the presence of different bases were described to afford two diastereomeric epoxy phosphonates in good yields and high diastereoselectivities. The diastereoselectivity of this reaction is easily controlled by changing the base. Accordingly, changing the base from Cs2CO3 to DBU changes the diatereomeric ratio (trans/cis) from 5/3 to 9/1. Furthermore, the treatment of trans isomer with DBU shows a complete conversion to the corresponding cis isomer. Additionally, these highly functionalized epoxyphosphonates are shown to be useful intermediates to give several reactions


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A regioselective approach to the synthesis of benzo[h][1,6]-naphthyridine and chromenopyrazinone derivatives was developed. The synthetic route to benzo[h][1,6]naphthyridines involves the N-propargylation of aromatic aminobenzaldehydes, followed by reaction with propargylamine in the presence of DBU (1,8-diazabicyclo[5.4.0] undec-7ene). For the synthesis of chromenopyrazine and chromeno-pyrazinone derivatives, the acetonitrile group was introduced to salicylaldehyde derivatives, and a DBU-promoted cyclizati...
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This microreview describes recent advances in asymmetric synthesis of aziridine derivatives, which have been published over the last two years.
A new approach for the synthesis of spiro and gem-dimethyl-substituted 1,4-oxazepines from N-propargylic beta-enaminones
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An efficient and general method for the synthesis of spiro-1,4-oxazepines and 3,3-dimethyl-1,4-oxazepines is reported. When treated with ZnI2 and AgSbF6 in refluxing DCE, cyclohexane-embedded N-propargylic beta-enaminones underwent 7-exo-dig cyclization to afford spiro-1,4-oxazepines, specifically 12-methylene-11-oxa-7-azaspiro[5.6]dodeca-7,9-dienes, in good to high yields. Accordingly, N-(1,1-dimethyl)propargylic beta-enaminones produced 3,3-dimethyl-1,4-oxazepines. Cyclization was found to be general for ...
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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.
Self condensation reaction of alpha-ketophosphonates
Göllü, Mehmet; Demir, Ayhan Sıtkı; Department of Chemistry (2007)
This thesis presents synthesis of tertiary α-hydroxy phosphonate derivatives. α-Ketophosphonates is known that they are both acyl anion precursors and electrophiles. In this work, α-ketophosphonates were used as both acyl anion precursors and electrophiles in the presence of catalytic amount of KCN. α-Ketophosphonates underwent benzoin-type condensation reaction.
Citation Formats
M. Emrullah, “ Novel annulation reactions for the synthesis of substituted pyrroles darzens reaction of acyl phosphonates with α-bromo ketones : selective synthesis of cis- and transepoxyphosphonates,” Ph.D. - Doctoral Program, Middle East Technical University, 2009.