Dang Y, Han Jimin, Chmiel Alyah F, Alektiar Sara N, Mikhael Myriam, Guzei Ilia A, Yeung Charles S, Wickens Zachary K
Department of Chemistry, University of Wisconsin─Madison, Madison, Wisconsin 53706, United States.
Discovery Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
J Am Chem Soc. 2024 Dec 25;146(51):35035-35042. doi: 10.1021/jacs.4c14421. Epub 2024 Dec 12.
Herein, we introduce a new platform for alkene carboxy-alkylation. This reaction is designed around CO addition to alkenes followed by radical polar crossover, which enables alkylation through carbanion attack on carbonyl electrophiles. We discovered that CO adds to alkenes faster than it reduces carbonyl electrophiles and that this reactivity can be exploited by accessing CO via hydrogen atom transfer from formate. This photocatalytic system transforms vinylarenes and carbonyl compounds into a diverse array of substituted γ-lactone products. Furthermore, indoles can be engaged through dearomative carboxy-alkylation, delivering medicinally relevant C(sp)-rich heterocyclic scaffolds. Mechanistic studies reveal that the active photocatalyst is generated through a photochemically induced reaction between the precatalyst and DMSO. Overall, we have developed a three-component alkene carboxy-alkylation reaction enabled by the use of formate as the CO precursor.
在此，我们介绍了一种用于烯烃羧基烷基化的新平台。该反应围绕一氧化碳加成到烯烃上，随后进行自由基极性交叉设计，这使得通过碳负离子对羰基亲电试剂的攻击实现烷基化成为可能。我们发现一氧化碳加成到烯烃上的速度比其还原羰基亲电试剂的速度快，并且这种反应活性可以通过从甲酸盐进行氢原子转移来获取一氧化碳加以利用。这种光催化体系将乙烯基芳烃和羰基化合物转化为各种各样的取代γ-内酯产物。此外，吲哚可以通过去芳香化羧基烷基化参与反应，生成具有药物相关性的富含C(sp)的杂环骨架。机理研究表明，活性光催化剂是通过前催化剂与二甲亚砜之间的光化学诱导反应生成的。总体而言，我们开发了一种以甲酸盐作为一氧化碳前体的三组分烯烃羧基烷基化反应。
