Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, People's Republic of China.
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319, United States.
J Am Chem Soc. 2021 Feb 24;143(7):2812-2821. doi: 10.1021/jacs.0c11896. Epub 2021 Feb 9.
Carboxylic acids, including amino acids (AAs), have been widely used as reagents for decarboxylative couplings. In contrast to previous decarboxylative couplings that release CO as a waste byproduct, herein we report a novel strategy with simultaneous utilization of both the alkyl and carboxyl components from carboxylic acids. Under this unique strategy, carboxylic acids act as bifunctional reagents in the redox-neutral carbocarboxylation of alkenes. Diverse, inexpensive, and readily available α-AAs take part in such difunctionalizations of activated alkenes via visible-light photoredox catalysis, affording a variety of valuable but otherwise difficult to access γ-aminobutyric acid derivatives (GABAs). Additionally, a series of dipeptides and tripeptides also participate in this photocatalytic carbocarboxylation. Although several challenges exist in this system due to the low concentration and quantitative amount of CO, as well as unproductive side reactions such as hydrodecarboxylation of the carboxylic acids and hydroalkylation of the alkenes, excellent regioselectivity and moderate to high chemoselectivity are achieved. This process features low catalyst loading, mild reaction conditions, high step and atom economy, and good functional group tolerance, and it is readily scalable. The resulting products are subject to efficient derivations, and the overall process is amenable to applications in the late-stage modification of complex compounds. Mechanistic studies indicate that a carbanion is generated catalytically and it acts as the key intermediate to react with CO, which is also generated catalytically and thus remains in low concentration. The overall transformation represents an efficient and sustainable system for organic synthesis, pharmaceutics, and biochemistry.
羧酸，包括氨基酸 (AAs)，已被广泛用作脱羧偶联反应的试剂。与先前释放 CO 作为废物副产物的脱羧偶联反应相反，我们在此报告了一种新颖的策略，同时利用羧酸的烷基和羧基部分。在这种独特的策略下，羧酸在烯烃的氧化还原中性碳羧化反应中充当双功能试剂。不同的、廉价的和易得的α-AAs 通过可见光光氧化还原催化参与活化烯烃的这种双官能化反应，从而提供各种有价值但难以获得的γ-氨基丁酸衍生物 (GABAs)。此外，一系列二肽和三肽也参与了这种光催化碳羧化反应。尽管由于 CO 的浓度低且定量、羧酸的加氢脱羧和烯烃的加氢烷基化等非生产性副反应的存在，该体系存在一些挑战，但仍实现了优异的区域选择性和中等至高的化学选择性。该过程具有低催化剂负载、温和的反应条件、高步骤和原子经济性以及良好的官能团耐受性，并且易于扩大规模。所得产物可进行有效的衍生化，并且整个过程适用于复杂化合物的后期修饰应用。机理研究表明，催化生成碳负离子，它是与 CO 反应的关键中间体，CO 也是催化生成的，因此浓度保持较低。总的转化代表了一种用于有机合成、制药和生物化学的高效和可持续的系统。
