Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals
Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals
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DOI：
10.1038/nature17438
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发表时间：
2016-04-14
期刊：
影响因子：
64.8
通讯作者：
Melchiorre, Paolo
中科院分区：
文献类型：
--
作者：
Murphy, John J.;Bastida, David;Melchiorre, Paolo
现代有机化学的一个重要目标是开发新的催化策略，用于形成可用于产生季立体中心的对映选择性碳-碳键。虽然通过利用极性反应性已经取得了相当大的进展（1），但自由基转化却远没有那么成功（2）。尽管开壳层中间体本质上是连接结构拥挤的碳的，因为它们的反应性仅受空间因素的轻微影响（3）。在这里，我们展示了光氧化还原（4）和不对称有机催化（5）的组合如何使对映选择性自由基共轭加成到β，β-二取代的环烯酮，以获得具有高保真度的季碳立体中心。我们成功的关键是设计的手性有机催化剂，含有氧化还原活性咔唑部分，驱动形成的亚胺离子和立体选择性捕获的光化学产生的碳为中心的自由基通过电子中继机制。我们证明了这种有机催化的自由基捕获策略的一般性与两套开放的壳层中间体，形成通过无关的光触发途径从现成的基板和光氧化还原催化剂-这种方法代表了亚胺离子活化（6）（一个成功的催化策略对映体选择性极性化学）在自由基反应领域的应用。
An important goal of modern organic chemistry is to develop new catalytic strategies for enantioselective carbon-carbon bond formation that can be used to generate quaternary stereogenic centres. Whereas considerable advances have been achieved by exploiting polar reactivity(1), radical transformations have been far less successful(2). This is despite the fact that open-shell intermediates are intrinsically primed for connecting structurally congested carbons, as their reactivity is only marginally affected by steric factors(3). Here we show how the combination of photoredox(4) and asymmetric organic catalysis(5) enables enantioselective radical conjugate additions to beta,beta-disubstituted cyclic enones to obtain quaternary carbon stereocentres with high fidelity. Critical to our success was the design of a chiral organic catalyst, containing a redox-active carbazole moiety, that drives the formation of iminium ions and the stereoselective trapping of photochemically generated carbon-centred radicals by means of an electron-relay mechanism. We demonstrate the generality of this organocatalytic radical-trapping strategy with two sets of open-shell intermediates, formed through unrelated light-triggered pathways from readily available substrates and photoredox catalysts-this method represents the application of iminium ion activation(6) (a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.