Yeni imidazolyum türü n-heterosiklik karbenlerin sentezleri ve heck reaksiyonu ile bazı heterohalkalı bileşiklerin türevlendirilmelerindeki uygulamaları
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Date
2010
Authors
Çetin, Meliha
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Publisher
Uludağ Üniversitesi
Abstract
2 İzoksazolinlerden, metoksit varlığında NHC' lerin hazırlanmaya çalışılması sırasında %100 de ile cis-3-metoksi-7-(metoksikarbonil)-2,7a-diaril-5-okso-2,3,5,7a-tetrahidro-1H-pirolo[1,2-e]imidazol-6-olatlara 3 çevrildikleri gösterilmiştir. 3'lerin asidik hidrolizleri kinetik kontrollü olarak metil 1-formil-4-hidroksi-5-okso-2-fenil-2-((arilamino)metil)-2,5-dihidro-1H-pirol-3-karboksilatların 6 oluşmasına yol açmıştır. Bu yapıların molekül içi transformillenmeleriyle karşılık gelen (E)- ve (Z)-metil 4-hidroksi-2-((N-(aril)formamido)metil)-5-okso-2-fenil-2,5-dihidro-1H-pirol-3-karboksilatların 7 oluştukları tespit edilmiş, bu dönüşümün substitüente bağlı olduğu (? ile uyumlu) belirlenerek, Hammett eşitliğiyle karakterize edilmiştir. Sıcaklığın etkisi araştırılmış ve aynı seriler için 50, 60 ve 70 oC' de ? ? ? sabitleri belirlenmiştir. Amid diastereomerik oranı [(E)-7]/[(Z)-7] substitüente bağlıdır ve log[(E)]/[(Z)]X = -??I + log[(E)]/[(Z)]X=H eşitliği ile ifade edilebilir.2 İzoksazolinler toluende kaynatıldıklarında 3,4-dihidro-2H-imidazol-1-ium-1-(1,2-bis-metoksikarbonil-2-okso-etanitler) 8' lere çevrilirler ve bu yapılar hızlıca eliminasyonla 3H-imidazol-1-ium-1-(1,2-bis-metoksikarbonil-2-okso-etanitler) 10 ve 1H-imidazolleri 11 verirler. C-6' da aromatik halkanın varlığı durumunda dönüşüm hızı azalır ve 10' ların verimi artar. Toluenden daha polar çözücülerde (DMSO v.b.) 2' ler ılıman koşullarda kantitatif olarak 11' lere dönüşürler. Daha az polar çözücülerde (CCl4 gibi) reaksiyon hızı düşer ve 10 ürününün verimi artar. C-2' de substitüent içermeyen ylidler 10 oda koşullarında Et3N beraberinde Ag2O veya AgNO3 ile muamele edilerek yüksek verimlerle C-2 metallenmiş 13 yapıları oluşturulmuştur. 3H-imidazol-1-ium-1-(1,2-bis-metoksikarbonil-2-okso-etanit) 10' ların gümüş kompleksleri, Ag(NHCE)(Et3N), oda koşullarında CH2Cl2 içinde Pd(CH3CN)2Cl2 veya Pd(AcO)2 ile muamele edilerek yüksek verimlerle karşılık gelen 3H-imidazol-1-ium-1-(1,2-bis-metoksikarbonil-2-okso-etanit)-Pd(II) komp- leksleri 14, Pd(NHCE)(Et3N)Cl, hazırlanmıştır. Çözücü polaritesine bağlı olarak yapıların Pd(NHCE)2 ve Pd(Et3N)2Cl2 olarak dengede bulundukları tespit edilmiştir. 14 Katalizöründeki substitüent ve reaktanların etkilerinin yanı sıra, çözücü polaritesinin de reaksiyon hızı üzerindeki etkisi araştırılmıştır.4-Fenil-1-aril-2,5-dihidro-1H-imidazol 3-oksitler 1 dehidrasyonla kantitatif olarak 4-fenil-1-aril-1H-imidazolleri 11 verirler. Bunların ?-haloesterler ve amidlerle alkillenmeleriyle karşılık gelen imidazolyum tuzları 16 oluşurlar. İn situ oluşturulmuş NHC' lerden oluşturulan gümüş kompleksleri 17 ve 18 üzerinden karşılık gelen Pd(II) kompleksleri 19 hazırlanmıştır.Hazırlanmış olan Pd-NHC komplekslerinin aktiviteleri Heck-Mizoroki kenetlenme reaksiyonlarında çalışılmıştır. Öncü katalizörler seçilerek optimizasyon işlemleri gerçekleştirilmiştir. TONmax için 350000 değerlerine ulaşılmıştır. Seçilen katalizörler, 2- benzil(metil)-4-fenilizokinolin-1(2H)-on, 2-fenilH-imidazo[1,2-a]piridin ve 1,3,5-trifenil-1H-imidazol-2(3H)-on' ların fonksiyonelleştirilmesinde kullanılmıştır.
Attempts to prepare NHC? s from isoxazolines 2 in the presence of methoxide revealed that at these conditions they rearrange to cis-3-methoxy-7-(methoxycarbonyl)-2,7a-diaryl-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolo[1,2-e]imida-zol-6-olates 3 with 100% de. The acidic hydrolysis of 3 led to kinetically controlled formation of methyl 1-formyl-4-hydroxy-5-oxo-2-phenyl-2-((arylamino)methyl)-2,5-dihydro-1H-pyrrole-3-carboxylates 6. The intramolecular transformylations of the latter to the corresponding (E)- and (Z)-methyl 4-hydroxy-2-((N-(aryl)formamido)methyl)-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylates 7 were shown to be substituent dependent (correlate with ?) and characterized by Hammett type equations. The effect of temperature was investigated and the ? constants determined for the same reaction series at 50, 60 and 70 oC. The amide diastereomeric ratio [(E)-7]/[(Z)-7] is substituent dependent and can be described by the equation log[(E)]/[(Z)]X = -??I + log[(E)]/[(Z)]X=H.Isoxazolines 2 undergo rearrangement to 3,4-dihydro-2H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanides) 8 which spontaneously undergo elimination to give 3H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanides) 10 or 1H-imidazoles 11 when heated in toluene at reflux. The presence of the aromatic ring at C-6 decelerated the conversion and enhanced the yield of 10. Solvents more polar than toluene (e.g. DMSO) provided quantitative conversion of 2 into 11 in mild conditions, while in less polar solvents such as CCl4, the reaction rate was lowered and the yield of 10 enhanced. C-2 unsubstituted ylides 10 were treated with Ag2O or AgNO3 in the presence of Et3N at room temperature to give C-2 metallated derivatives 13 in excellent yields. The silver complexes of 3H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanides) 10, Ag(NHCE)(Et3N), were treated with Pd(CH3CN)2Cl2 or Pd(AcO)2 in CH2Cl2 at room temperature to give the corresponding 3H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanide)-Pd(II) complexes 14, Pd(NHCE)(Et3N)Cl, in high yields. Depending on the solvent polarity the latter complexes were proved to exist in equilibrium with Pd(NHCE)2 and Pd(Et3N)2Cl2. The effect of substituents on the catalyst 14 and reactants as well as the solvent polarity on the reaction rate were investigated.4-Phenyl-1-aryl-2,5-dihydro-1H-imidazole 3-oxides 1 were dehydrated quantitatively to 4-phenyl-1-aryl-1H-imidazoles 11. The alkylation of the latter with ?-haloesters and amides provides the corresponding imidazolium salts 16. The silver complexes of in situ formed NHCs from 16 were prepared and converted to the corresponding Pd(II) complexes 19.The catalytic activities of the prepared PdNHC complexes were screened in Heck-Mizoroki coupling reactions. Lead catalysts were selected and optimized. TONmax of 350000 were achieved. The selected catalysts were used in the functionalization of 2-benzyl(methyl)-4-phenylisoquinolin-1(2H)-one, 2-phenylH-imidazo[1,2-a]pyridine and 1,3,5-triphenyl-1H-imidazol-2(3H)-one.
Attempts to prepare NHC? s from isoxazolines 2 in the presence of methoxide revealed that at these conditions they rearrange to cis-3-methoxy-7-(methoxycarbonyl)-2,7a-diaryl-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolo[1,2-e]imida-zol-6-olates 3 with 100% de. The acidic hydrolysis of 3 led to kinetically controlled formation of methyl 1-formyl-4-hydroxy-5-oxo-2-phenyl-2-((arylamino)methyl)-2,5-dihydro-1H-pyrrole-3-carboxylates 6. The intramolecular transformylations of the latter to the corresponding (E)- and (Z)-methyl 4-hydroxy-2-((N-(aryl)formamido)methyl)-5-oxo-2-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylates 7 were shown to be substituent dependent (correlate with ?) and characterized by Hammett type equations. The effect of temperature was investigated and the ? constants determined for the same reaction series at 50, 60 and 70 oC. The amide diastereomeric ratio [(E)-7]/[(Z)-7] is substituent dependent and can be described by the equation log[(E)]/[(Z)]X = -??I + log[(E)]/[(Z)]X=H.Isoxazolines 2 undergo rearrangement to 3,4-dihydro-2H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanides) 8 which spontaneously undergo elimination to give 3H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanides) 10 or 1H-imidazoles 11 when heated in toluene at reflux. The presence of the aromatic ring at C-6 decelerated the conversion and enhanced the yield of 10. Solvents more polar than toluene (e.g. DMSO) provided quantitative conversion of 2 into 11 in mild conditions, while in less polar solvents such as CCl4, the reaction rate was lowered and the yield of 10 enhanced. C-2 unsubstituted ylides 10 were treated with Ag2O or AgNO3 in the presence of Et3N at room temperature to give C-2 metallated derivatives 13 in excellent yields. The silver complexes of 3H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanides) 10, Ag(NHCE)(Et3N), were treated with Pd(CH3CN)2Cl2 or Pd(AcO)2 in CH2Cl2 at room temperature to give the corresponding 3H-imidazol-1-ium-1-(1,2-bis-methoxycarbonyl-2-oxo-ethanide)-Pd(II) complexes 14, Pd(NHCE)(Et3N)Cl, in high yields. Depending on the solvent polarity the latter complexes were proved to exist in equilibrium with Pd(NHCE)2 and Pd(Et3N)2Cl2. The effect of substituents on the catalyst 14 and reactants as well as the solvent polarity on the reaction rate were investigated.4-Phenyl-1-aryl-2,5-dihydro-1H-imidazole 3-oxides 1 were dehydrated quantitatively to 4-phenyl-1-aryl-1H-imidazoles 11. The alkylation of the latter with ?-haloesters and amides provides the corresponding imidazolium salts 16. The silver complexes of in situ formed NHCs from 16 were prepared and converted to the corresponding Pd(II) complexes 19.The catalytic activities of the prepared PdNHC complexes were screened in Heck-Mizoroki coupling reactions. Lead catalysts were selected and optimized. TONmax of 350000 were achieved. The selected catalysts were used in the functionalization of 2-benzyl(methyl)-4-phenylisoquinolin-1(2H)-one, 2-phenylH-imidazo[1,2-a]pyridine and 1,3,5-triphenyl-1H-imidazol-2(3H)-one.
Description
Keywords
Dipolar halkakatılma, Nitronlar, Ylidler, İzoksazolinler, İmidazoizoksazolinler, Çevrilme, Kaskat reaksiyonları, NHCler, Kenetlenme reaksiyonları, NHC-metal kompleksleri, Dipolar cycloaddition, Nitrones, Ylides, Isoxazolines, Imidazoisoxazolines, Rearrangement, Cascade reactions, NHCs, Coupling reactions, NHC-metal complexes
Citation
Çetin, M. (2010). Yeni imidazolyum türü n-heterosiklik karbenlerin sentezleri ve heck reaksiyonu ile bazı heterohalkalı bileşiklerin türevlendirilmelerindeki uygulamaları. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Fen Bilimleri Enstitüsü.