Etkili Bir Kiral Katalizör Sentezi: Enantiyoselektif Michael Reaksiyonlarında Kullanılması

Kiral sentez, enantioselektif sentez veya stereoselektif sentez olarak da adlandırılan asimetrik sentez, stereoseçici olarak bir veya daha fazla kiral bileşiklerin oluşturulmasını sağlayan organik sentez biçimidir. Bir molekülün farklı enantiyomerleri veya diastereomerleri çoğu zaman farklı biyolojik aktiviteye sahip olduğu için asimetrik sentez özellikle ilaç endüstrisinde ve organik kimya alanında önemlidir. Kiral katalizör kullanımı ise, son yıllarda araştırmacılar tarafından tercih edilen en etkili yöntemlerden birisi olup; normal şartlarda rasemik karışım şeklinde ürün veren bir tepkimeye etki ederek, ağırlıklı olarak bir stereoizomeri elde etmeye yönelik bir stratejidir. Bu çalışmada ilk önce tetraoksakaliks[2]aren[2]triazin resorsinol ve siyanürik klorid kullanılarak sentezlendi ve sonra bu başlangıç maddesi (R)-(-)-2-fenilglisinol ile reaksiyona sokularak tetraoksakaliks[2]aren[2]triazin bazlı kiral bir bileşik elde edildi. Tetraoksakaliks[2]aren[2]triazinin karakterizasyonu, literatürde bulunan ${}^1H$ ve ${}^{13}C$ NMR spektroskopi değerleri ile karşılaştırılarak yapıldı. Daha sonra, hidroksil ve amino grubuna sahip yeni bir organokatalizör tasarlandı ve sentezlendi. Yeni katalizörün yapısı ${}^1H$ ve ${}^{13}C$ NMR spektroskopisi, elemental analiz ve çevirme açısı teknikleriyle aydınlatıldı. Sentezlenen kiral bileşik dimetilmalonatın farklı nitroalkenlerle olan enantiyoselektif Michael katılma reaksiyonlarında katalizör olarak kullanıldı ve çok iyi enantiyoselektivite elde edildi. Reaksiyonu etkileyen farklı faktörler (çözücü, sıcaklık, katalizör yüzdesi) incelenerek reaksiyon şartları optimize edildi. En iyi reaksiyon şartları oda sıcaklığı, çözücü olarak toluen ve %10 mol katalizör olarak bulundu. Kiral katalizörün katalitik etkisi HPLC’de kiral kolonlar kullanılarak belirlendi. Reaksiyon sonucunda oluşan ürünler yüksek verim (%93) ve yüksek enantiyomerik fazlalık (%95) ile (S) formunda elde edildi.

An Efficient Synthesis of Chiral Catalyst: Application in Enantioselective Michael Addition Reactions

Asymmetric synthesis, also called stereoselective synthesis, chiral synthesis or enantioselective synthesis, is a form of organicsynthesis which presentes one or more new elements of chirality. Use of catalysts is one of the most effective methods preferred bythe researchers in recent years. It causes to the preferential formation of a stereoisomer rather than a constitutional isomer. In thisstudy, tetraoxocalix[2]arene[2]triazine was synthesized firstly by using resorcinol and cyanuric chloride and then this starting materialwas derivatized with (R)-(-)-2-phenylglycinol to obtain tetraoxocalix[2]arene[2]triazine based chiral compound. Characterization oftetraoxocalix[2]arene[2]triazine was done by ${}^1H$ and ${}^{13}C$ NMR spectroscopy which is depicted in literature. Then, new organocatalyst,which possess an amino and a hydroxyl group, was designed and synthesized. The structure of the receptor characterized by FTIR, 1Hspectroscopy,${}^{13}C$ NMR spectroscopy, optical rotation and elemental analysis measurement was also included. The newly preparedtetraoxocalix[2]arene[2]triazine derivative was employed as a chiral ligand in the enantioselective Michael addition ofdimethylmalonate to conjugated nitroalkenes and good to excellent enantioselectivities were obtained. Various factors, (solvent,temperature, catalyst %) were examined and the reactions were optimized. The best condition for the Michael addition reaction wasdetermined as room temperature, toluene as solvent and 10 mol% of heteroatom-bridged calixaromatic based chiral catalyst asorganocatalyst loading. The catalytic efficiency of the chiral catalyst was analyzed by HPLC using chiral columns. The correspondingadducts were generally obtained in (S)-forms with great yields (up to 93%) and enantioselectivities (up to 95% ee).

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