Brønsted酸催化炔酰胺分子内氢烷氧化/Claisen重排反应  

Brønsted Acid-Catalyzed Intramolecular Hydroalkoxylation/Claisen Rearrangement of Ynamides

作　　者：翟彤仪 葛畅 钱鹏程[2] 周波[1] 叶龙武[1,3] Zhai Tongyi;Ge Chang;Qian Pengcheng;Zhou Bo;Ye Longwu(College of Chemistry and Chemical Engineering,Xiamen University,Xiamen 361005;b College of Chemistry&Materials Engineering,Wenzhou University,Wenzhou 325035;c State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032)

机构地区：[1]厦门大学化学化工学院,厦门361005 [2]温州大学化学与材料工程学院,温州325035 [3]中国科学院上海有机化学研究所金属有机化学国家重点实验室,上海200032

出　　处：《化学学报》2023年第9期1101-1107,共7页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.22125108,22121001);厦门大学校长基金(No.20720210002);国家基础科学人才培养基金(No.J1310024)资助。

摘　　要：报道了一例Brønsted酸催化的炔酰胺分子内氢烷氧化/Claisen重排反应合成八元环内酰胺化合物的方法.首先,炔酰胺在Brønsted酸活化条件下形成烯酮亚胺鎓中间体,并通过氢键及离子对的方式与分子内的羟基作用,进而发生氢烷氧化/Claisen重排串联反应生成八元环内酰胺化合物.此外,利用手性Brønsted酸催化的动力学拆分策略对该不对称反应进行了初步探究,并成功合成了几类手性八元环内酰胺产物.该无金属催化的方法不仅操作简单、反应条件温和,还具有良好的官能团兼容性.这项研究为合成具有重要生物活性的八元环内酰胺骨架提供了实用的新方法.A Brønsted acid-catalyzed intramolecular hydroalkoxylation/Claisen rearrangement of ynamides for the synthesis of eight-membered lactams is presented.Firstly,the keteniminium intermediate was generated from the activation of ynamide by Brønsted acid,which could interact with intramolecular hydroxy group through hydrogen bonding and ion pairing effects.Then,the tandem hydroalkoxylation/Claisen rearrangement took place and produced eight-membered lactams.Meanwhile,preliminary studies were conducted into the chiral Brønsted acid-catalyzed kinetic resolution,and several chiral eight-membered lactams were successfully synthesized.Other notable features of this metal-free method include the simple procedure,mild reaction conditions and good functional group compatibility.This research provides a practical method for the synthesis of biologically important eight-membered lactam skeletons.Accordingly,MsOH(5 mol%,0.005 mmol,0.32μL)was added to the solution of ynamide(1 equiv.,0.1 mmol)in dry PhCl(4 mL)at room temperature.The reaction mixture was then stirred at 60℃and the progress of the reaction was monitored by thin layer chromatography(TLC).Upon completion,the reaction was quenched with Et3N(0.005 mmol,0.7μL),concentrated and purified by chromatography on silica gel(eluent:petroleum ether/ethyl acetate,V∶V=5∶1),to afford the desired eight-membered lactam.Under this condition,a series of ynamides with different substituents worked smoothly to provide the corresponding eight-membered lactams efficiently.Furthermore,chiral Brønsted acid(10 mol%,0.005 mmol,3.5 mg)and H_(2)O(0.05 mmol,0.9μL)were added to the solution of ynamide(1 equiv.,0.05 mmol)in PhCl(2 mL)at-20℃and the progress of the reaction was monitored by TLC.Upon completion,the reaction was quenched with Et3N(0.005 mmol,0.75μL),concentrated and purified by chromatography on silica gel(eluent:petroleum ether/ethyl acetate,V∶V=5∶1),to afford the chiral eight-membered lactam and chiral substrate.Also,a plausible mechanism involving the hydrogen bo

关 键 词：炔酰胺 Brønsted酸催化 CLAISEN重排 中环内酰胺 动力学拆分 

分 类 号：O621.251[理学—有机化学]