Rh(III)-Catalyzed Mild Coupling of Nitrones and Azomethine Imines with Alkylidenecyclopropanes via C–H Activation: Facile Access to Bridged Cycles

Bridged cycles are an important class of structural motif in various biologically active molecules. Rh­(III)-catalyzed C–H activation of nitrones and azomethine imines in the context of dipolar addition with alkylidenecyclopropanes (ACPs) have been realized. By taking advantage of the ring strain in ACPs, the reaction with aryl nitrones delivered bridged [3.2.1] bicyclic isoxazolidines, and reaction with azomethine imines afforded bridged tricyclic pyrazolones under the same conditions, where both the nitrone and azomethine imine act as a dipolar directing group. All the reactions occurred under mild conditions with broad substrates scope, high efficiency, and >20:1 diastereoselectivity. The synthetic applications of this protocol have also been demonstrated.

桥环（bridged cycles）是各类生物活性分子中一类重要的结构基元。铑(III)催化的硝酮与甲亚胺亚胺的C-H活化偶极加成反应，在与亚烷基环丙烷（alkylidenecyclopropanes, ACPs）的反应体系中已被成功实现。借助ACPs的环张力特性，该催化体系中与芳基硝酮的反应可生成桥环[3.2.1]双环异噁唑烷；而在相同条件下与甲亚胺亚胺的反应则得到桥环三环吡唑啉酮，其中硝酮与甲亚胺亚胺均同时充当偶极导向基团。所有反应均在温和条件下进行，底物适用范围广、反应效率优异，且非对映选择性大于20:1。该合成策略的合成应用亦已得到验证。