有机催化靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应  

Organocatalytic Enantioselective Mannich-type Addition of 5H-Oxazol-4-ones to Isatin Derived Ketimines

作　　者：黄秋红 李文军[2] 李鑫 HUANG Qiuhong;LI Wenjun;LI Xin(College of Chemistry,Nankai University,Tianjin 300071,China;Department of Medicinal Chemistry,School of Pharmacy,Qingdao University,Qingdao 266021,China;Haihe Laboratory of Sustainable Chemical Transformations,Tianjin 300192,China)

机构地区：[1]南开大学化学学院,天津300071 [2]青岛大学药学院药物化学系,青岛266021 [3]物质绿色创造与制造海河实验室,天津300192

出　　处：《高等学校化学学报》2022年第8期65-74,共10页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:22193011,21971120,21933008)资助。

摘　　要：研究了手性磷酸催化的靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应,以良好至优秀的收率(高达97%)、对映选择性(高达99%e.e.)以及非对映选择性(均>20∶1 d.r.)得到一系列含噁唑酮骨架的手性3,3′-二取代氧化吲哚化合物.该反应可以进行扩大化和衍生反应.Chiral 3,3′-disubstituted oxindoles are widely present in a variety of natural products and bioactive mole⁃cules.And the nature of substituents and the absolute configuration of the stereo center at the C3 position have a great effect on the bioactivities of these chiral oxindoles.Therefore,it is of great significance to develop efficient and practi⁃cal methods to construct chiral 3,3′-disubstituted oxindole compounds.In particular,the enantioselective Mannich-type addition of isatin derived imines is one of the most straightforward method for forging chiral 3,3′-disubstituted oxindole compounds.Based on previous experiments,it was found that the 5H-oxazol-4-ones,which had diverse reactive sites and could be easily converted into importantα-alkyl-α-hydroxy derivatives,were potential candidate nucleophile for enantioselective Mannich-type addition reaction.Herein,we reported the first chiral phosphoric acid catalyzed enantioselective Mannich-type addition reaction of isatin derived ketimines with 5H-oxazol-4-ones.Various of electron-withdrawing or electron-donating substituted isatin derived ketimines and 5H-oxazol-4-ones.Various of electron-withdrawing or electron-donating substituted isatin derived ketimines and 5H-oxazol-4-ones could be better adapt to the reaction conditions to construct chiral 3,3′-disubstituted oxindole compounds with good to excellent yields(up to 97%),enantioselectivities(up to 99%e.e.)and diastereoselectivities(all>20∶1 d.r.).What’s more,the reaction could be scaled up,and the synthetic utility of the desired chiral 3,3′-disubstituted oxindoles was proved by transformations.

关 键 词：有机催化 靛红衍生酮亚胺 噁唑酮 Mannich型加成反应 手性3 3′-二取代氧化吲哚化合物 

分 类 号：O626.25[理学—有机化学]