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

Abstract

Asymmetric synthesis, also called stereoselective synthesis, chiral synthesis or enantioselective synthesis, is a form of organic synthesis which presentes one or more new elements of chirality. Use of catalysts is one of the most effective methods preferred by the researchers in recent years. It causes to the preferential formation of a stereoisomer rather than a constitutional isomer. In this study, tetraoxocalix[2]arene[2]triazine was synthesized firstly by using resorcinol and cyanuric chloride and then this starting material was derivatized with (R)-(-)-2-phenylglycinol to obtain tetraoxocalix[2]arene[2]triazine based chiral compound. Characterization of tetraoxocalix[2]arene[2]triazine was done by 1H and 13C 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, 1H spectroscopy, 13C NMR spectroscopy, optical rotation and elemental analysis measurement was also included. The newly prepared tetraoxocalix[2]arene[2]triazine derivative was employed as a chiral ligand in the enantioselective Michael addition of dimethylmalonate 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 was determined as room temperature, toluene as solvent and 10 mol% of heteroatom-bridged calixaromatic based chiral catalyst as organocatalyst loading. The catalytic efficiency of the chiral catalyst was analyzed by HPLC using chiral columns. The corresponding adducts were generally obtained in (S)-forms with great yields (up to 93%) and enantioselectivities (up to 95% ee).

Keywords

• Asymmetric synthesis
• Organocatalysis
• Michael addition
• Stereoselectivity

Etkili Bir Kiral Katalizör Sentezi: Enantiyoselektif Michael Reaksiyonlarında Kullanılması

Öz

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 13C NMR spektroskopi değerleri ile karşılaştırılarak yapıldı. Daha sonra, hidroksil ve amino grubuna sahip yeni bir organokatalizör tasarlandı ve sentezlendi. Yeni katalizörün yapısı 1H ve 13C 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.

Anahtar Kelimeler

• Asimetrik sentez
• Organokatalizör
• Michael katılma
• Stereoselektivite

Kaynakça

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