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

我们发现了一个金催化的多米诺反应，包括三键的活化、亚胺氮的6-外显环化、亚甲亚胺酰化和烯胺环化。炔基亚胺酯可以作为唯一的非对映体转化为吲哚嘧啶。对苯基薄荷酯衍生物进行了x射线晶体学分析，揭示了产物的构型及其对立体选择性的影响机理。然而，吡咯吲哚嗪形成的最后一步，即烯胺环化根本无法进行，因为外显烯胺通过与芳香环的偶联而异构化为不合适的内显烯胺。通过分子间方法对烯胺环化步骤进行研究，以避免不期望的异构化，我们最终认识到三氟乙酯作为亲电试剂在一锅法中得到羟基吡咯的效果最好。基于这些发现，目前正在进行对桃金娘素的合成研究。

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.