College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China.
Institute of New Materials & Industrial Technology, Wenzhou University, Wenzhou 325035, China.
J Org Chem. 2020 Oct 16;85(20):13004-13014. doi: 10.1021/acs.joc.0c01654. Epub 2020 Sep 30.
A novel palladium-catalyzed protocol for the synthesis of 9-arylacridines via tandem reaction of 2-(arylamino)benzonitrile with arylboronic acids in water has been developed with good functional group tolerance. The present synthetic route could be readily scaled up to gram quantity without difficulty. This methodology was further extended to the synthesis of a 4'-OH derivative, which showed estrogenic biological activity. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular Friedel-Crafts acylation and dehydration to acridines.
已开发出一种通过 2-(芳氨基)苯甲腈与芳基硼酸在水中的串联反应合成 9-芳基吖啶的新型钯催化方法，具有良好的官能团耐受性。目前的合成路线可以毫不困难地很容易扩展到克级规模。该方法进一步扩展到 4'-OH 衍生物的合成，该衍生物表现出雌激素生物活性。初步的机理实验表明，这种转化涉及芳基钯物种对腈的亲核加成，生成芳基酮中间体，然后进行分子内傅克酰化和脱水生成吖啶。
