School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
The GSK Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham, Jubilee Campus, Nottingham NG7 2TU, United Kingdom.
J Am Chem Soc. 2023 Feb 8;145(5):2773-2778. doi: 10.1021/jacs.2c12699. Epub 2023 Jan 31.
The formation of carbon-carbon bonds via the intermolecular addition of alkyl radicals to alkenes is a cornerstone of organic chemistry and plays a central role in synthesis. However, unless specific electrophilic radicals are involved, polarity matching requirements restrict the alkene component to be electron deficient. This limits the scope of a fundamentally important carbon-carbon bond forming process that could otherwise be more universally applied. Herein, we introduce a strategy that formally overcomes this electronic limitation. Vinyl sulfonium ions are demonstrated to react with carbon-centered radicals, giving adducts that undergo or sequential nucleophilic displacement to provide products that would be inaccessible via traditional methods. The broad generality of this strategy is demonstrated through the derivatization of unmodified complex bioactive molecules.
通过烷基自由基与烯烃的分子间加成形成碳-碳键是有机化学的基石，在合成中起着核心作用。然而，除非涉及特定的亲电自由基，否则极性匹配要求限制了烯烃组分必须是缺电子的。这限制了原本可以更广泛应用的重要碳-碳键形成过程的范围。在此，我们引入了一种策略，正式克服了这一电子限制。乙烯基锍离子被证明可以与碳中心自由基反应，生成加成物，然后进行[1,2]-或[1,3]-亲核取代，从而提供通过传统方法无法获得的产物。通过对未经修饰的复杂生物活性分子的衍生化，证明了该策略的广泛通用性。
