Lutovsky Grace A, Gockel Samuel N, Bundesmann Mark W, Bagley Scott W, Yoon Tehshik P
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.
These authors contributed equally.
Chem. 2023 Jun 8;9(6):1610-1621. doi: 10.1016/j.chempr.2023.04.008. Epub 2023 May 4.
Carboxylic acids are valuable building blocks for pharmaceutical discovery because of their chemical stability, commercial availability, and structural diversity. Decarboxylative coupling reactions enable versatile functionalization of these feedstock chemicals, but many of the most general methods require prefunctionalization of carboxylic acids with redox-active moieties. These internal oxidants can be costly, their installation impedes rapid library synthesis, and their use results in environmentally problematic organic byproducts. We report herein a method for the direct decarboxylative cross-coupling of native carboxylic acids with nucleophilic coupling partners mediated by inexpensive, terrestrially abundant, and nontoxic Fe(III) salts. This method involves an initial photochemical decarboxylation followed by radical-polar crossover, which enables the construction of diverse carbon-carbon, carbon-oxygen, and carbon-nitrogen bonds with remarkable generality.
羧酸因其化学稳定性、商业可得性和结构多样性，是药物研发中重要的基础原料。脱羧偶联反应能实现这些原料化学品的多功能化，但许多最常用的方法需要用氧化还原活性基团对羧酸进行预官能化。这些内氧化剂成本高昂，其引入阻碍了快速文库合成，且使用它们会产生对环境有问题的有机副产物。我们在此报道一种由廉价、地球上储量丰富且无毒的铁（III）盐介导的，使天然羧酸与亲核偶联伙伴直接进行脱羧交叉偶联的方法。该方法包括初始的光化学脱羧，随后是自由基 - 极性交叉，能够以显著的通用性构建多种碳 - 碳、碳 - 氧和碳 - 氮键。
