Photocatalytic α-arylation of cyclic ketones
Photocatalytic α-arylation of cyclic ketones
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DOI：
10.1038/s44160-021-00021-0
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发表时间：
2022-02-01
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影响因子：
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通讯作者：
Gianetti, Thomas L.
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文献类型：
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作者：
Hossain, Md Mubarak;Shaikh, Aslam C.;Gianetti, Thomas L.
使用芳基卤化物的羰基化合物的直接α-芳基化代表了合成各种有用化合物的关键结构单元的有力方法。存在许多合成方法来形成C（sp2）-C（sp3）键，尽管酮的温和且无金属的直接α-芳基化仍然是具有挑战性的转化。在这里，我们报告了一个绿光介导的α-芳基化酮从容易获得的芳基卤化物通过激活的C（sp2）-X键（X = I，Br，Cl）和α-羰基C（sp3）-H键在一个单一的光催化循环。该方法具有反应条件温和、操作简便、官能团耐受性广等特点。重要的是，多克光催化反应的令人印象深刻的结果巩固了这种方法作为一种潜在的实用和有吸引力的方法用于放大工业目的的优势。该反应的实用性和范围通过几种原料化学品的正式合成得到进一步证明，这些原料化学品在商业上昂贵，但对于合成许多药物制剂至关重要。温和且无金属的酮的直接α-芳基化反应长期以来一直是一种具有挑战性的转化。目前，人们已经开发出一种无金属光氧化还原方法，利用富电子吖啶离子在低能绿色光下光活化C（sp2）-X键，并催化环酮的α-芳基化反应。这种方法是一种用于合成药物化合物的多克和可持续的方法。
The direct alpha-arylation of carbonyl compounds using aryl halides represents a powerful method to synthesize critical building blocks for diverse useful compounds. Numerous synthetic methods exist to forge C(sp2)-C(sp3) bonds although mild and metal-free direct alpha-arylation of ketones remains a challenging transformation. Here we report a green-light-mediated alpha-arylation of ketones from readily available aryl halides via activation of a C(sp2)-X bond (X = I, Br, Cl) and an alpha-carbonyl C(sp3)-H bond in a single photocatalytic cycle. This approach is characterized by its mild reaction conditions, operational simplicity and wide functional group tolerance. Importantly, the impressive outcome of the multigram photocatalytic reaction underpins the strength of this method as a potentially practical and attractive approach for scale-up industrial purposes. The utility and scope of this reaction were further demonstrated by formal syntheses of several feedstock chemicals that are commercially expensive but critical for synthesizing numerous pharmaceutical agents.Mild and metal-free direct alpha-arylation of ketones has long been a challenging transformation. Now, a metal-free photoredox approach has been developed using electron-rich acridinium ions to photoactivate C(sp2)-X bonds under low-energy green light and to catalyse the alpha-arylation of cyclic ketones. This approach is a multigram and sustainable methodology for the synthesis of pharmaceutical synthons.