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

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.

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

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 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 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.