Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States.
J Am Chem Soc. 2022 Aug 31;144(34):15871-15878. doi: 10.1021/jacs.2c07170. Epub 2022 Aug 19.
The concurrent installation of C-C and C-N bonds across alkene frameworks represents a powerful tool to prepare motifs that are ubiquitous in pharmaceuticals and bioactive compounds. To construct such prevalent bonds, most alkene difunctionalization methods demand the use of precious metals or activated alkenes. We report a metal-free, photochemically mediated imino-alkylation of electronically diverse alkenes to install both alkyl and iminyl groups in a highly efficient manner. The exceptionally mild reaction conditions, broad substrate scope, excellent functional group tolerance, and facile one-pot reaction protocol highlight the utility of this method to prepare privileged motifs from readily available alkene and acid feedstocks. One key and striking feature of this transformation is that an electrophilic trifluoromethyl radical is equally efficient with both electron-deficient and electron-rich alkenes. Additionally, dispersion-corrected density functional theory (DFT) and empirical investigations provide detailed mechanistic insight into this reaction.
在烯烃框架中同时构建 C-C 和 C-N 键是一种强大的工具，可以制备在药物和生物活性化合物中普遍存在的基序。为了构建这些常见的键，大多数烯烃双官能化方法都需要使用贵金属或活化烯烃。我们报告了一种无金属、光介导的亚氨基烷基化反应，可高效地在电子多样化的烯烃上同时引入烷基和亚氨基基团。该反应条件非常温和，底物范围广泛，对官能团具有良好的耐受性，并且可以方便地一锅法进行反应，这些特点突出了该方法在从易得的烯烃和酸原料制备优势基序方面的实用性。该转化的一个关键和显著特点是，亲电三氟甲基自由基对缺电子和富电子烯烃的效率相同。此外，色散校正密度泛函理论（DFT）和经验研究为该反应提供了详细的机理见解。
