Anti-Markovnikov alcohols via epoxide hydrogenation through cooperative catalysis
Anti-Markovnikov alcohols via epoxide hydrogenation through cooperative catalysis
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DOI：
10.1126/science.aaw3913
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发表时间：
2019-05
期刊：
影响因子：
56.9
通讯作者：
Chengbo Yao;Tobias Dahmen;A. Gansäuer;J. Norton
中科院分区：
文献类型：
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作者：
Chengbo Yao;Tobias Dahmen;A. Gansäuer;J. Norton
马可夫尼科夫落在铬和钛的环开应变三角环氧化物是一种通用的方法，以制造醇。然而，这些反应是有限的，因为它们倾向于把氧留在取代更重的碳上，这与马尔可夫尼科夫规则是一致的。Yao等人现在表明，一对催化剂协同工作可以扭转这种选择性模式。钛催化剂将环撬开，而铬催化剂激活并释放氢。在一种不同寻常的机制扭曲中，铬复合物似乎在循环的不同阶段传递一个氢原子、一个质子和一个电子。《科学》，本期第764页铬和钛配合物的催化作用是将氢加到环氧化物中取代较多的碳上形成醇。环氧化合物的打开通常需要亲电活化，随后的亲核（SN2）攻击较少取代的碳导致醇具有马尔可夫尼科夫区选择性。我们描述了一种将钛二茂烯催化环氧化物开孔与铬催化氢活化和自由基还原相结合的抗马尔可夫尼科夫醇协同催化方法。二茂钛通过形成高度取代的自由基来增强反马尔可夫尼科夫区选择性。铬催化剂依次从氢分子中转移氢原子、质子和电子，避免氢化物转移到不需要的位置，从而实现100%的原子经济。对相互连接的催化循环的每个步骤分别进行了确认。
Markovnikov falls to chromium and titanium Ring opening of strained triangular epoxides is a versatile method for making alcohols. However, these reactions are limited by their tendency to leave the oxygen on the more heavily substituted carbon, in accord with the Markovnikov rule. Yao et al. now show that a pair of catalysts working cooperatively can invert this selectivity pattern. A titanium catalyst pries the ring open while a chromium catalyst activates and delivers hydrogen. In an unusual mechanistic twist, the chromium complex appears to deliver a hydrogen atom, a proton, and an electron at different stages of the cycle. Science, this issue p. 764 Catalysis by chromium and titanium complexes forms alcohols by adding hydrogen to the more-substituted carbon of epoxides. The opening of epoxides typically requires electrophilic activation, and subsequent nucleophilic (SN2) attack on the less substituted carbon leads to alcohols with Markovnikov regioselectivity. We describe a cooperative catalysis approach to anti-Markovnikov alcohols by combining titanocene-catalyzed epoxide opening with chromium-catalyzed hydrogen activation and radical reduction. The titanocene enforces the anti-Markovnikov regioselectivity by forming the more highly substituted radical. The chromium catalyst sequentially transfers a hydrogen atom, proton, and electron from molecular hydrogen, avoiding a hydride transfer to the undesired site and resulting in 100% atom economy. Each step of the interconnected catalytic cycles was confirmed separately.