Double Regioselective Asymmetric C-Allylation of Isoxazolinones: Iridium-Catalyzed N-Allylation Followed by an Aza-Cope Rearrangement.
Double Regioselective Asymmetric C-Allylation of Isoxazolinones: Iridium-Catalyzed N-Allylation Followed by an Aza-Cope Rearrangement.
复制标题
DOI：
10.1002/anie.201710940
复制
发表时间：
2018-01
影响因子：
--
通讯作者：
Stefan Rieckhoff;J. Meisner;J. Kästner;W. Frey;R. Peters
中科院分区：
文献类型：
--
作者：
Stefan Rieckhoff;J. Meisner;J. Kästner;W. Frey;R. Peters
异恶唑啉酮类化合物是一类具有生物活性和合成活性的杂环化合物，但长期以来一直不能通过不对称催化得到对映体富集形式。除了对映体选择性方法的不足之外，异恶唑啉酮的官能化通常受到由于杂环内各种亲核中心的竞争而引起的区域选择性问题的困扰。我们报告的第一个区域和对映选择性的异恶唑啉酮的C-烯丙基化。这些发生在有利于线性烯丙基化产物的高区域选择性下，尽管使用Ir亚磷酰胺催化剂，其通常导致支链异构体。我们的研究表明，这一结果是通过初始区域和对映选择性的N-烯丙基化，以提供一个支链烯丙基中间体，然后通过自发的[3，3]-重排，导致手性转移的反应级联的结果。
Isoxazolinones are biologically and synthetically interesting densely functionalized heterocycles, which for a long time were not accessible in enantioenriched form by asymmetric catalysis. Next to the deficit of enantioselective methods, the functionalization of isoxazolinones is often plagued by regioselectivity issues due to the competition of various nucleophilic centers within the heterocycles. We report the first regio- and enantioselective C-allylations of isoxazolinones. These occur with high regioselectivity in favor of the linear allylation products, although Ir phosphoramidite catalysts were used, which commonly results in branched isomers. Our studies suggest that this outcome is the result of a reaction cascade via an initial regio- and enantioselective N-allylation to provide a branched allyl intermediate, followed by a spontaneous [3,3]-rearrangement resulting in chirality transfer.