Development of domino cyclization reaction for one-pot synthesis of pyrroloindolizines and its application to total syntheses of related alkaloids

我们发现金催化的多米诺骨牌反应包括三键的活化、亚胺氮的6-外开环、甲亚胺叶立德的生成和烯胺的环合，炔基亚氨基酯可以作为唯一的非对映异构体转化为中氮杂环。对苯基薄荷酯衍生物进行了X-射线晶体分析，揭示了产物的构型和影响立体选择性的机理。然而，由于外烯胺通过与芳环的共轭异构化为不适当的内烯胺，最终形成吡咯吲哚二氮的最后一步--烯胺环化反应根本无法进行。用分子间方法对烯胺环化步骤进行了研究，排除了不希望发生的异构化反应，最终发现在一锅法工艺中，三氟乙酯作为电泳剂给出羟基吡咯的效果最好。基于这些发现，桃金娘碱类的合成研究目前正在进行中。

We could find a gold-catalyzed domino reaction including an activation of triple bond, 6-exo-dig cyclization from imine nitrogen, generation of azomethine ylide, and enamine cyclization.Alkynyl iminoesters could be transformed into indolizines as a sole diastereomer. The X-ray crystallographic analysis on phenylmenthyl ester derivative revealed the configuration of the products and the mechanism on the observed stereoselectivities. However, the enamine cyclization, the final step for pyrroloindolizine formation, could not proceed at all because of the isomerization of the exo-enamine into the inappropriate endo-enamine via a conjugation with aromatic ring. After the investigations on the enamine cyclization step with intermolecular approach for a preclusion of undesired isomerization, we finally realized that trifluoroethyl ester worked best as an electrophile to give hydroxypyrroles in one-pot process. Based on these findings, synthetic studies on myrmicarins are now in progress.