Cobalt-Catalyzed Intramolecular Olefin Hydroarylation Leading to Dihydropyrroloindoles and Tetrahydropyridoindoles
Cobalt-Catalyzed Intramolecular Olefin Hydroarylation Leading to Dihydropyrroloindoles and Tetrahydropyridoindoles
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DOI：
10.1002/anie.201305151
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发表时间：
2013-08-12
影响因子：
16.6
通讯作者：
Yoshikai, Naohiko
中科院分区：
文献类型：
--
作者：
Ding, Zhenhua;Yoshikai, Naohiko
具有二氢吡咯并吲哚和四氢吡啶并吲哚核心骨架的稠合三环吲哚存在于药学相关的小分子中，例如L-888，607、Ro 32-0432和MK-7246（图1）。[1]后一种骨架也与吲哚生物碱有关，如士的宁、马钱子碱和长春胺。因此，有效和选择性的反应，允许建设这样的稠环系统可能是有用的合成方法。作为一个值得注意的例子，Bergman和Ellman的小组通过铑催化的醛亚胺导向的C1 H2活化/N-烯丙基吲哚的分子内氢化芳基化实现了生物活性二氢吡咯并吲哚衍生物的合成，包括手性非外消旋衍生物（方案1a）。[2]沿着这个特定的例子，他们已经广泛地开发了带有烯烃系链的芳族、杂芳族和烯烃底物的铑催化的C13 H活化反应[3-6]，并证明了它们在碳环和杂环的靶向合成中的实用性，[7]而Murai小组早期报道了关于铑和铑催化的1，5-和1，6-二烯衍生物通过螯合辅助的烯属C2 H4活化。[8]As如方案1a所示，铑催化剂对于与带有烯丙基系链的底物的5-内型环化作用最有效。另一方面，高烯丙基系链由于两种固有可行的环化模式（即，5-外对6-内）以及在加氢芳基化之前容易的烯烃异构化而造成区域选择性问题，并且尚未用于吲哚平台。比同烯丙基更长的烯烃系链尚未用于任何芳族或杂芳族平台上。[9]我们在此报告我们的发展钴-N-杂环卡宾（NHC）催化的分子内烯烃加氢芳基化吲哚底物轴承homoallyl或bishomoallyl栓。补充铑催化的范围，本发明的催化体系允许5-外型-、6-内型-和6-外型环化，以在温和的反应条件下提供一系列二氢吡咯并吲哚和四氢吡啶并吲哚衍生物。目前的研究已经导致了一对夫妇的显着的发现，即，1）通过选择的NHC配体和2）季碳中心的形成，这是迄今为止未知的烯烃加氢芳基化通过螯合辅助C1 H1 H活化的区域发散形成的五元和六元环。我们的研究开始于吲哚1a的分子内环化，吲哚1a在C3位上具有醛亚胺部分，在N原子上具有高烯丙基基团（表1）。根据我们最近对钴催化的螯合辅助的分子间烯烃加氢芳基化的研究，[10，11]使用10摩尔%的CoBr 2、10-20摩尔%的
Fused tricyclic indoles with dihydropyrroloindole and tetrahydropyridoindole core skeletons are present in pharmaceutically relevant small molecules, such as L-888,607, Ro 32-0432, and MK-7246 (Figure 1).[1] The latter skeleton is also relevant to indole alkaloids, such as strychnine, brucine, and vincamine. Consequently, efficient and selective reactions allowing construction of such fused cyclic systems could be useful synthetic methods. As a notable example, the group of Bergman and Ellman achieved the synthesis of biologically active dihydropyrroloindole derivatives, including a chiral non-racemic derivative, through rhodium-catalyzed, aldimine-directed CÀH activation/intramolecular hydroarylation of N-allylindoles (Scheme 1a).[2] Along with this particular example, they have extensively developed rhodium-catalyzed CÀH activation reactions of aromatic, heteroaromatic, and olefinic substrates bearing alkene tethers [3–6] and demonstrated their utility in target-oriented synthesis of carbo-and heterocycles,[7] while the Murai group earlier reported seminal studies on rhodium-and ruthenium-catalyzed intramolecular cyclization of 1, 5-and 1, 6-diene derivatives through chelation-assisted olefinic CÀH activation.[8]As shown in Scheme 1 a, the rhodium catalysis works most efficiently for 5-endo-type cyclization with substrates bearing allylic tethers. On the other hand, homoallylic tethers pose a regioselectivity issue because of the two intrinsically feasible modes of cyclization (that is, 5-exo vs. 6-endo) as well as facile olefin isomerization prior to hydroarylation, and have not been employed on the indole platform. Alkene tethers that are longer than a homoallyl group have not been used on any aromatic or heteroaromatic platforms.[9] We report herein on our development of cobalt-N-heterocyclic carbene (NHC)-catalyzed intramolecular olefin hydroarylation of indole substrates bearing homoallyl or bishomoallyl tethers. Complementing the scope of the rhodium catalysis, the present catalytic systems allow 5-exo-, 6-endo-, and 6-exo-type cyclization to afford a series of dihydropyrroloindole and tetrahydropyridoindole derivatives under mild reaction conditions. The present study has led to a couple of notable findings, namely, 1) regiodivergent formation of five-and sixmembered rings by the choice of the NHC ligand and 2) formation of a quaternary carbon center, which have been hitherto unknown for olefin hydroarylation through chelation-assisted CÀH activation. Our study began with intramolecular cyclization of indole 1a bearing an aldimine moiety on the C3 position and a homoallyl group on the N atom (Table 1). In light of our recent study on cobalt-catalyzed, chelation-assisted intermolecular olefin hydroarylation,[10, 11] screening of reaction conditions was performed using 10 mol% of CoBr2, 10–20 mol%