有机催化吲哚与环状酮亚胺膦酸酯的傅-克反应合成含手性季碳胺基膦酸衍生物（英文）

发布时间：2018-06-03 16:01

  本文选题：傅-克反应 + 季碳胺基膦酸酯　； 参考：《催化学报》2017年05期

【摘要】：在有机合成中,季碳中心的构建始终是一项充满挑战的课题.含手性季碳中心的胺基膦酸化合物以其多样的生物活性,如酶抑制剂、抗真菌剂、抗菌剂和抗病毒剂等,受到了科研工作者的广泛关注.目前已有许多合成策略报道,其中亲核试剂与α-酮亚胺膦酸酯的不对称加成策略为含手性季碳中心胺基膦酸衍生物的合成提供了一条简洁有效的路径,但是却鲜有报道,已有的报道也仅局限于乙酰氰、丙酮、硝基甲烷和芳基硼酸作亲核试剂.为满足多样的手性胺基膦酸衍生物的合成需求,新的合成策略和亲核源仍有待进一步发展.值得一提的是,不对称傅-克反应是一种非常有效的构建碳-碳键的合成方法,并已有广泛报道.基于吲哚与亚胺底物的傅-克反应经验,我们研究组发展了一种有机催化吲哚与环状酮亚胺膦酸酯傅-克反应合成含手性季碳胺基膦酸衍生物的方法,使用的有机催化剂是手性磷酸.通过对溶剂、催化剂和温度的筛选发现,使用在3,3′-位引入吸电子的3,5-二三氟甲基苯基取代的H8-BINOL衍生的手性磷酸作催化剂,反应温度为30℃,溶剂为均三甲苯时,最高能以98%对映选择性得到含手性季碳胺基膦酸酯化合物.该反应操作简单,条件温和,不仅适用于吲哚衍生物,对吡咯也能取得较好结果.总之,该方法提供了一条简洁有效的合成手性胺基膦酸衍生物的途径.
[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 伪 -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，

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