Department of Chemistry, Emory University , Atlanta, Georgia 30322, United States.
J Org Chem. 2014 Jan 3;79(1):392-400. doi: 10.1021/jo4026622. Epub 2013 Dec 20.
Model studies dealing with the rhodium(II)-catalyzed carbenoid insertion/cyclization/cycloaddition cascade of several α-diazo dihydroindolinones have been carried out as an approach to the alkaloid mersicarpine. The cascade reaction of α-diazo dihydroindolinone 21 proceeded in high yield with excellent diastereoselectivity to give cycloadduct 22, which possesses the required stereochemistry of the two adjacent quaternary carbon centers present in mersicarpine. The overall reaction enabled the rapid assemblage of a polycyclic ring system that contains three new stereocenters and three continuous quaternary carbons in a single operation in high yield with excellent diastereoselectivity. The 3-indolinone derivative 36 was eventually formed from cycloadduct 22 by an acid-induced hydrolysis of 22 to give 23, which was subsequently converted in several steps to 36. The synthesis of this compound constitutes a successful construction of the tricyclic core of mersicarpine. Reduction of the nitrile group of 36 followed by a subsequent reductive cyclization/ring-opening aromatization cascade, as was found to occur with the related compound 29, will be employed for an eventual synthesis of demethylmersicarpine.
作为一种获得生物碱 mersicarpine 的方法，我们进行了一系列涉及几种 α-重氮二氢吲哚酮的铑（II）催化碳烯插入/环化/加成级联的模型研究。α-重氮二氢吲哚酮 21 的级联反应以高产率和优异的非对映选择性进行，得到具有 mersicarpine 中两个相邻季碳原子所需立体化学的环加成产物 22。该反应能够在单一操作中快速组装一个多环体系，其中包含三个新的立体中心和三个连续的季碳原子，产率高，非对映选择性优异。通过酸诱导水解 22 得到 23，随后将环加成产物 22 转化为 36，最终从环加成产物 22 中形成 3-吲哚酮衍生物 36。该化合物的合成成功构建了 mersicarpine 的三环核心。正如相关化合物 29 所发现的那样，36 的腈基的还原随后进行随后的还原环化/开环芳构化级联反应，将用于最终合成去甲基 mersicarpine。
