【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.更多还原

【Abstract】 Chiral 3,3′-disubstituted oxindoles are widely present in a variety of natural products and bioactive molecules. 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 practical methods to construct chiral 3,3′-disubstituted oxindole compounds. In particular,the enantioselective Mannichtype 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 important α-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.更多还原