本文選題：傅-克反應 + 季碳胺基膦酸酯　； 參考：《催化學報》2017年05期

【摘要】：在有機合成中,季碳中心的構(gòu)建始終是一項充滿挑戰(zhàn)的課題.含手性季碳中心的胺基膦酸化合物以其多樣的生物活性,如酶抑制劑、抗真菌劑、抗菌劑和抗病毒劑等,受到了科研工作者的廣泛關(guān)注.目前已有許多合成策略報道,其中親核試劑與α-酮亞胺膦酸酯的不對稱加成策略為含手性季碳中心胺基膦酸衍生物的合成提供了一條簡潔有效的路徑,但是卻鮮有報道,已有的報道也僅局限于乙酰氰、丙酮、硝基甲烷和芳基硼酸作親核試劑.為滿足多樣的手性胺基膦酸衍生物的合成需求,新的合成策略和親核源仍有待進一步發(fā)展.值得一提的是,不對稱傅-克反應是一種非常有效的構(gòu)建碳-碳鍵的合成方法,并已有廣泛報道.基于吲哚與亞胺底物的傅-克反應經(jīng)驗,我們研究組發(fā)展了一種有機催化吲哚與環(huán)狀酮亞胺膦酸酯傅-克反應合成含手性季碳胺基膦酸衍生物的方法,使用的有機催化劑是手性磷酸.通過對溶劑、催化劑和溫度的篩選發(fā)現(xiàn),使用在3,3′-位引入吸電子的3,5-二三氟甲基苯基取代的H8-BINOL衍生的手性磷酸作催化劑,反應溫度為30℃,溶劑為均三甲苯時,最高能以98%對映選擇性得到含手性季碳胺基膦酸酯化合物.該反應操作簡單,條件溫和,不僅適用于吲哚衍生物,對吡咯也能取得較好結(jié)果.總之,該方法提供了一條簡潔有效的合成手性胺基膦酸衍生物的途徑.
[Abstract]:In organic synthesis, the construction of quaternary carbon centers is always a challenging subject. Amino phosphonic acid compounds containing chiral quaternary carbon centers have attracted wide attention due to their diverse biological activities, such as enzyme inhibitors, antifungal agents, antimicrobial agents and antiviral agents. At present, many synthesis strategies have been reported, among which the asymmetric addition strategy of nucleophilic reagent and 偽 -keto-imidronate provides a simple and effective route for the synthesis of chiral quaternary carbon-centered amino phosphonic acid derivatives, but it is rarely reported. Previous reports have been limited to acetyl cyanide, acetone, nitromethane and aryl boric acid as nucleophilic reagents. In order to meet the needs of synthesis of various chiral amino phosphonic acid derivatives, new synthesis strategies and nucleophilic sources need to be further developed. It is worth mentioning that asymmetric Friedel-Ke reaction is a very effective method for the synthesis of carbon-carbon bond, and has been widely reported. Based on the experience in the Friedel-gram reaction of indole-imine substrates, our team developed an organic catalytic method for the synthesis of chiral quaternary carbamido-phosphonic acid derivatives by the Friede-gram reaction of indoles with cycloketoimine phosphonate. The organic catalyst used is chiral phosphoric acid. Through the screening of solvent, catalyst and temperature, it was found that the chiral phosphoric acid derived from the H8-BINOL derivative of 3o 5- difluoromethylphenyl substituted H8-BINOL was used as catalyst when the reaction temperature was 30 鈩，

本文編號：1973364