상전이 촉매 반응을 통한 α-substituted-α-benzyl malonate의 새로운 비대칭 합성법 개발

Abstract

Chiral α-malonates는 생리학적인 활성을 가지는 약리활성물질과 천연물의 chiral α-quaternary carbon centers의 구조합성에 광범위하게 사용된다. 본 연구실에서는 상전이 촉매, PTC라 불리는 상전이 촉매반응을 이용하여 높은 수준의 입체선택적인 합성을 보고했다. 선행연구에서 5가지 malonate 물질들을 PTC α-benzylation 하였고, 2,2-diphenylethyl malonate 을 최종물질로 선택하여 반응 조건을 최적화하였다. -40oC, 50% aqueous potassium hydroxide와 toluene 용매조건으로 PTC를 진행하였을 때 높은 광학수율(>99% ee)을 얻었으며 다양한 electrophiles 을 사용하여 실험하였다. 본 연구에서는 diphenylethyl malonate의 α위치에 다양한 치환기가 있는 phenyl을 도입하여 electronic effect를 밝혀내고자 하였다. 결과적으로, electron donating group 이 electron withdrawing group 보다 높은 광학수율(>90%)을 얻었으며 이는 촉매와의 상호작용에서 기인한 것으로 생각된다.

Chiral α-malonates are widely used for the structural synthesis of chiral α-quaternary carbon centers of physiologically active pharmaceuticals and natural products. In our laboratory, we reported a high level of stereoselective synthesis results using a phase transfer catalyst (PTC). In previous studies, 5 malonate materials were PTC α-benzylation and 2,2-diphenylethyl malonate was selected as the final material to optimize the reaction conditions. High optical yield (up to 99% ee) was obtained when PTC was reacted at -40°C, 50% aqueous potassium hydroxide and toluene solvent conditions and various electrophiles were used. In this study, we tried to clarify the electronic effect by using phenyl with various substituents at α position of diphenylethyl malonate. In conclusion, the electron- donating group (EDG) has higher optical yield (up to 96% ee) than the electron-withdrawing group (EWG), which is thought to be due to the interaction with the catalyst.