Selective Bromination of sp3 C ∼ H Bonds by Organophotoredox Catalysis
Selective Bromination of sp3 C ∼ H Bonds by Organophotoredox Catalysis
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DOI：
10.1002/ajoc.201300169
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发表时间：
2014-04-01
影响因子：
2.7
通讯作者：
Tan, Choon-Hong
中科院分区：
文献类型：
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作者：
Kee, Choon Wee;Chan, Ke Min;Tan, Choon-Hong
我们报道，通过使用低负载量的曙红二钠盐（一种廉价的有机染料）作为光氧化还原催化剂，可以通过可见光光氧化还原催化实现脂肪族和苄基 sp(3) CH 键的溴化。光源为低功率家用灯，反应无需惰性气氛和无水溶剂即可进行。易于处理的 CBr4 是溴的来源，而吗啉是该反应所必需的。对该机制的初步实验和计算研究强烈表明 N-吗啉基自由基负责 CH 激活步骤。这使我们提出这是一个自由基接力反应，其中寿命较长的吗啉自由基是通过热力学有利的反应从相对更瞬态的 CBr3 自由基产生的。从自由基捕获实验中获得了这种 N-自由基存在的额外证据。该反应对富电子氢原子的强烈偏好，以及对 CH 键周围空间环境的高敏感性，使得溴化能够发生在同一分子上相对较强的 CH 键（通过键解离焓量化）上。 (+)-香紫苏内酯和乙酸酯保护的雌酮的溴化证明了利用该反应实现复杂分子中 sp(3) CH 键的温和和区域选择性溴化的潜力。
We report that bromination of aliphatic and benzylic sp(3) CH bonds can be achieved with visible light photoredox catalysis by using a low loading of EosinY disodium salt, an inexpensive organic dye, as a photoredox catalyst. The light source is a low-power household lamp and the reaction can be performed without the need of an inert atmosphere and anhydrous solvent. Easy-to-handle CBr4 is the source of bromine and morpholine is necessary for the reaction. Preliminary experimental and computational studies on the mechanism strongly suggest that an N-morpholino radical is responsible for the CH activation step. This led us to propose that this is a radical relay reaction, in which a longer-lived morpholine radical is generated from a CBr3 radical, which is relatively more transient, by a thermodynamically favorable reaction. Additional evidence for the existence of such an N-radical was obtained from radical trapping experiments. The strong preference of this reaction for electron-rich hydrogen atoms, and the high sensitivity to the steric environment around the CH bond enables bromination to occur on the relatively stronger CH bond (as quantified by bond dissociation enthalpy) on the same molecule. The potential for utilizing this reaction to achieve mild and regioselective bromination of sp(3) CH bonds in complex molecules is exemplified by the bromination of (+)-sclareolide and acetate-protected estrone.