Institute of Chemical Research of Catalonia (ICIQ), Barcelona Institute of Science and Technology, Avda. Països Catalans 16, 43007 Tarragona, Spain.
Photogreen Laboratory, Department of Chemistry, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy.
Nature. 2016 Apr 14;532(7598):218-22. doi: 10.1038/nature17438.
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, radical transformations have been far less successful. 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. Here we show how the combination of photoredox and asymmetric organic catalysis enables enantioselective radical conjugate additions to β,β-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 (a successful catalytic strategy for enantioselective polar chemistry) within the realm of radical reactivity.
现代有机化学的一个重要目标是开发用于对映选择性碳-碳键形成的新催化策略，这些策略可用于生成季立体中心。尽管通过利用极性反应性已经取得了相当大的进展，但自由基转化却远没有那么成功。尽管事实是，开壳中间体本质上适合连接结构拥挤的碳原子，因为它们的反应性仅受空间因素的轻微影响。在这里，我们展示了如何将光氧化还原和不对称有机催化结合起来，实现β,β-二取代环状烯酮的对映选择性自由基共轭加成，以高保真度获得具有高立体选择性的季碳立体中心。我们成功的关键是设计了一种包含氧化还原活性咔唑部分的手性有机催化剂，该催化剂通过电子中继机制驱动亚胺离子的形成和光化学产生的碳中心自由基的对映选择性捕获。我们通过两组开壳中间体证明了这种有机催化自由基捕获策略的通用性，这两组中间体是通过与光触发途径无关的、从易得的底物和光氧化还原催化剂形成的——这种方法代表了亚胺离子活化（对映选择性极性化学的成功催化策略）在自由基反应性领域的应用。
