Nickel-catalyzed enantioselective arylation of pyridinium ions: harnessing an iminium ion activation mode.
Nickel-catalyzed enantioselective arylation of pyridinium ions: harnessing an iminium ion activation mode.
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DOI：
10.1002/anie.201303994
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发表时间：
2013-08-26
期刊：
影响因子：
--
通讯作者：
Doyle AG
中科院分区：
文献类型：
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作者：
Chau ST;Lutz JP;Wu K;Doyle AG
在过渡金属催化的C-C键形成中接合阳离子底物如亚胺鎓和氧代碳鎓离子的能力是一项具有挑战性的任务，最近已经成功应用。[1]在这种情况下，我们报告说，低价镍催化剂促进前所未有的铃木宫浦交叉偶联反应与烯丙基N，O-和O，O-缩醛基板。[2，3]机理研究表明，硼酸介导烯丙基C-O活化，在所得亚胺鎓或氧代碳鎓离子中间体与Ni催化剂之间发生氧化加成（方案1a）。[4]过渡金属催化剂可以氧化插入到这些前手性中间体的证明为反应设计和对映选择性合成提供了许多令人兴奋的可能性。在此，我们证明了这种活化模式能够通过Negishi与N-酰基吡啶离子的交叉偶联对映选择性合成α取代的2，3-二氢-4-吡啶酮（方案1b）。α-取代哌啶是生物活性小分子中最常见的骨架之一，也是天然产物和药物合成的结构单元。[5]以碳为中心的亲核试剂对活性吡啶的立体选择性加成是制备这些核心结构的一个特别有吸引力的途径。[6]Comins和Charette小组的前期工作建立了使用化学计量的手性酰化剂来控制C-C键形成的立体化学结果的可能性。[7，8]然而，对于有机金属试剂与前手性N-酰基/烷基吡啶鎓离子的催化对映选择性加成，仅描述了两个实例。[9]这两种反应都可能通过将手性[M]-R物质添加到前手性吡啶鎓盐（M= Cu或Rh）中来进行。因此，该策略限于与高度亲核R基团或高度亲电吡啶离子的反应。作为氧化
The ability to engage cationic substrates such as iminium and oxocarbenium ions in transition-metal-catalyzed C–C bond formation is a challenging task that has recently seen successful application.[1] In this context, we reported that a low-valent Ni catalyst facilitates unprecedented Suzuki–Miyaura cross-coupling reactions with allylic N, O-and O, O-acetal substrates.[2, 3] Mechanistic studies revealed that boronic acids mediate allylic C–O activation, with oxidative addition occurring between the resulting iminium or oxocarbenium ion intermediate and the Ni catalyst (Scheme 1a).[4] The demonstration that a transition-metal catalyst can oxidatively insert into these prochiral intermediates offers a number of exciting possibilities for reaction design and enantioselective synthesis. Herein, we demonstrate that this activation mode enables the enantioselective synthesis of αsubstituted 2, 3-dihydro-4-pyridones by Negishi cross-coupling with N-acyl pyridinium ions (Scheme 1b). α-Substituted piperidines are among the most prevalent scaffolds in biologically active small molecules, and also serve as building blocks for natural product and pharmaceutical synthesis.[5] The stereoselective addition of carbon-centered nucleophiles to activated pyridines is a particularly attractive route to these core structures.[6] Seminal work from the groups of Comins and Charette established the possibility of using stoichiometric chiral acylating agents to control the stereo-chemical outcome of C–C bond formation.[7, 8] However, only two examples have been described for the catalytic enantio-selective addition of organometallic reagents to prochiral N-acyl/alkyl pyridinium ions.[9] Both of these reactions likely proceed through the addition of a chiral [M]-R species into a prochiral pyridinium salt (M= Cu or Rh). As such, the strategy is limited to reactions with either highly nucleophilic R groups or highly electrophilic pyridinium ions. As the oxidative