Stereoselective Synthesis of γ‑Lactams from Imines and Cyanosuccinic Anhydrides

A reaction between imines and anhydrides has been developed with chiral disubstituted anhydrides and chiral imines. The synthesis of highly substituted γ-lactams with three stereogenic centers, including one quaternary center, proceeds at room temperature in high yield and with high diastereoselectivity in most cases. Enantiomerically pure alkyl-substituted anhydrides proceed with no epimerization, thus providing access to enantiomerically pure penta-substituted lactam products.本工作开发了亚胺（imines）与酸酐（anhydrides）之间的反应，该反应以手性双取代酸酐（chiral disubstituted anhydrides）与手性亚胺（chiral imines）为底物。反应可于室温下进行，多数情况下可实现高产率与高非对映选择性，合成含有三个立体异构中心（stereogenic centers）、其中一个为季碳中心（quaternary center）的高取代γ-内酰胺（γ-lactams）。采用对映体纯烷基取代酸酐参与反应时不会发生差向异构化（epimerization），因此可获得对映体纯的五取代内酰胺产物。