双功能激活-催化的不对称反转电子的Diels-Alder反应研究：构建手性大环分子的新途径

反转电子要求的Diels-Alder反应(IEDDAR)是立体选择性构建六元功能化环状结构最有效的方法之一。目前报道催化模式：1）利用路易斯酸催化剂（金属化合物或有机小分子）LUMO-活化双烯体的策略；2）利用烯胺HOMO-活化亲双烯体的策略。然而，据我们所知，HOMO亲双烯体和LUMO双烯体共同激活-催化的方法还没有报道。本项目拟利用单一有机催化剂通过同时HOMO-活化亲双烯体和LUMO-活化双烯体的双功能策略，实现不对称IEDDAR的催化反应，为不对称IEDDAR提供了一种新的思路及潜在的方法。此外，大环类化合物是有机化合物中非常重要的一类，许多重要的天然产物及生物活性手性化合物均具有大环的结构骨架。本项目的另一个目的就是，将发展的双功能激活-催化的IEDDAR应用于手性合成大环类化合物之中，为具有重要生物活性的大环类化合物的手性构建提供了一种新的便利的方法。

The asymmetric inverse-electron demand Diels-Alder reaction (IEDDAR)is among the most powerful protocols for the stereoselective construction of functionalized crabocycles. At present, it can be achieved by two strategies: (i) the LUMO-dienes-activation strategy by the catalysis of either metal-based or organic molecules as Lewis acids; (ii) the HOMO-dienophiles-activation strategy by an enamine activation. However, to our best knowledge, a more efficient bifunctional HOMO-dienophiles and LUMO-dienes controlling activation strategy has not yet been development. In this study, we document the highly enantioselective bifunctional catalytic IEDDAR via an unprecedented dual HOMO-dienophiles and LUMO-dienes controlling pathway with a single reactive catalyst. It provides a new platform and potential method for organocatalytic asymmetric inverse-electron demand Diels-Alder reaction. In addition, macrolide core is a privileged structural element that is featured in a large series of bioactive naturally occuring alkaloids and pharmaceutically relevant assays. Herein, this asymmetric process provides a promising method for the construction of enantioenriched macrolides, and the synthetic route is more convenient for practical use.