金/铱接力催化炔基酰胺环化/不对称烯丙基苄基化串联反应  

Gold/Iridium Catalyzed Alkynylamide Cyclization/Asymmetric Allylic Benzylation Cascade Reaction

作　　者：王瑞祥 赵庆如 顾庆[2] 游书力 Wang Rui-Xiang;Zhao Qing-Ru;Gu Qing;You Shu-Li(Chang-Kung Chuang Institute,East China Normal University,Shanghai 200062,China;State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China)

机构地区：[1]华东师范大学庄长恭研究所,上海200062 [2]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5期431-434,共4页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.21821002,22031012,22071260)资助。

摘　　要：苄基亲核试剂参与的不对称烯丙基取代反应可以快速构筑含苄基片段的手性分子,受到了有机化学家的广泛关注.其中使用5-亚甲基二氢噁唑作为苄基亲核试剂等同体,可以实现形式上的不对称苄位烯丙基取代反应.然而由于5-亚甲基二氢噁唑化合物稳定性较差,合成也存在一定困难,对于发展高效的不对称苄位烯丙基取代反应提出了新挑战.本工作发展了金/铱催化的炔基酰胺环化/不对称烯丙基苄基化串联反应.首先金催化炔基酰胺环化生成5-亚甲基二氢噁唑,随后亲核进攻烯丙基铱中间体,以良好的收率(49%~87%)以及优秀的对映选择性控制(98%~>99%ee)得到芳基苄位烯丙基取代的手性分子.Asymmetric allylic substitution reactions involving benzyl nucleophilic reagents can rapidly construct chiral molecules containing benzyl fragments,which has attracted widespread attention from organic chemists.Formal asymmetric allylic benzylation reactions have been achieved by utilizing methylene oxazole as an equivalent of benzyl nucleophile.However,the development of highly efficient asymmetric allylic benzylation reactions remains a great challenge mainly due to the poor stability and synthetic difficulty of methylene oxazole.In this work,we have developed gold-and iridiumcatalyzed alkynylamide cyclization/asymmetric allylic benzylation cascade reactions.In the presence of gold-carbene complex(Au1)and the combination of[Ir(cod)Cl]2 and(Sa)-Carreira ligand,a wide range of enantioenriched oxazole derivatives,bearing a benzylic stereogenic center,were obtained in 49%~87%yields with 98%~>99%ee.A general procedure is described as the following:To a dried Schlenk tube were added[Ir(cod)Cl]2(5.4 mg,0.008 mmol,4 mol%),(Sa)-L1(16.2 mg,0.032 mmol,16 mol%)and 1,2-dichloroethane(1 mL)under argon atmosphere.The mixture was stirred at room temperature for 15 minutes to give a chiral iridium complex solution.Under an argon atmosphere,alkynylamide(0.2 mmol,1.0 equiv.),allyl alcohol(0.4 mmol,2.0 equiv.),Au1(0.02 mmol,12.4 mg,10 mol%),Fe(OTf)2(0.2 mmol,70.6 mg,1.0 equiv.)and 3Åmolecular sieves(80.0 mg)were added to another dry Schlenk tube,and then the above-prepared iridium catalyst was added.The reaction mixture was stirred at 40℃until the starting materials were consumed(monitored by thin layer chromatography,TLC).The mixture was quenched with water(5 mL),and extracted with dichloromethane(5 mL×3).The combined organic layers were dried over anhydrous Na2SO4,filtered,and then concentrated in vacuo to afford the crude product.The residue was purified by column chromatography(V(petroleum ether)/V(ethyl acetate)=15/1 or 10/1)to afford product 3.

关 键 词：不对称催化 烯丙基苄基化 炔酰胺环化 串联反应 金 铱 

分 类 号：O621.251[理学—有机化学]