由碘介導甲醇/乙醇間斷異-納札羅夫環化反應之共軛二烯以獲得高取代性之二烷氧基環戊烯衍生物

Abstract

在1942年，科學家發現了納札羅夫(Nazarov)反應。然而在接下來的近八十年中，由於對其合成意義缺乏認識，這個反應並未受到太多關注。直到過去十年才有大量的研究被報導出來，原因在於此反應對於天然化合物或醫藥分子中所含的五圓環衍生物而言，是個十分有效的合成途徑。本研究即是以納札羅夫(Nazarov)反應的延伸 ：「間斷異-納札羅夫(Interrupted Iso-Nazarov)」進行研究，探討不同溶劑作為親核劑在合環時產生的加成反應。使用二烯醛(Dienals)架構的分子與碘作為催化劑，搭配不同溶劑進行間斷異-納札羅夫合環反應，並利用聚焦式微波合成儀將反應時間大幅縮短，同時提升反應產率。利用親核基捕捉環戊烯中間體 ，進一步從結果探討捕捉加成時的不同立體位向，最終得到高度立體選擇性的不同取代基之二烷氧基環戊烯衍生物。Scientists have discovered the “Nazarov reaction” almost eighty years ago. However, for almost eighty years, it didn't receive much attention due to a lack of recognition regarding its synthetic significance. It was only in the past decade that a substantial amount of research has been reported, as this reaction has proven to be a highly effective synthetic pathway for pentacyclic derivatives found in natural compounds and pharmaceutical molecules. This research is an extension of the Nazarov reaction, which is "Interrupted Iso-Nazarov". The goal of the study is to investigate the addition reaction of different solvents as nucleophilic groups during the cyclization. We carried an iodine-catalyzed"interrupted iso-Nazarov" reaction of dienals in various solvents. Furthermore, we used "Microwave reactor" to substantially reduce reaction time and boost the yield of products. We attempted to use the nucleophile to trap the cyclopentene intermediate and further explored the different stereo orientations when trapping the intermediate from the results. Fortunately, highly stereoselective cyclopentene derivatives with different substituents were finally obtained at the end.