Mizuta Satoshi, Kitamura Kanami, Kitagawa Ayako, Yamaguchi Tomoko, Ishikawa Takeshi
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo, Nagasaki, 852-8521, Japan.
Department of Chemistry, Biotechnology and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima, 890-0065, Japan.
Chemistry. 2021 Apr 1;27(19):5930-5935. doi: 10.1002/chem.202004769. Epub 2021 Jan 26.
Silver-promoted C-F bond formation in α-bromoamides by using AgF under mild conditions is reported. This simple method enables access to tertiary, secondary, and primary alkyl fluorides involving biomolecular scaffolds. This transformation is applicable to primary and secondary amides and shows broad functional-group tolerance. Kinetics experiments revealed that the reaction rate increased in the order of 3°>2°>1° α-carbon atom. In addition, it was found that the acidic amide proton plays an important role in accelerating the reaction. Mechanistic studies suggested generation of an aziridinone intermediate that undergoes subsequent nucleophilic addition to form the C-F bond with stereospecificity (i.e., retention of configuration). The synthesis of sterically hindered alcohols and ethers by using Ag is also demonstrated. Examples of reactions of α-bromoamides with O nucleophiles are presented.
据报道，在温和条件下使用AgF可实现银促进α-溴代酰胺中C-F键的形成。这种简单的方法能够制备涉及生物分子支架的叔、仲和伯烷基氟化物。该转化反应适用于伯酰胺和仲酰胺，并且对官能团具有广泛的耐受性。动力学实验表明，反应速率按3°>2°>1°α-碳原子的顺序增加。此外，发现酸性酰胺质子在加速反应中起重要作用。机理研究表明生成了氮杂环丁烷酮中间体，该中间体随后进行亲核加成以立体专一性地（即构型保持）形成C-F键。还展示了使用Ag合成空间位阻醇和醚的方法。给出了α-溴代酰胺与O亲核试剂反应的实例。
