Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
J Org Chem. 2009 Dec 4;74(23):9158-64. doi: 10.1021/jo901906b.
As a convenient and direct synthesis of 1,2-dihydroisoquinolines, the gold(I)-catalyzed intramolecular hydroamination of (2-alkynyl)benzyl carbamates has been developed. The reaction with cationic gold(I) complex [AuCl(PPh(3))/AgNTf(2)] proceeded at room temperature, giving the desired 6-endo adducts. The addition of alcohol efficiently promoted the reaction, and the amount of the catalyst could be reduced to 1 mol %. However, the alkynes bearing either an electron-deficient aryl group or an alkyl group resulted in predominant production of 5-exo adducts. In such cases, use of a bulky gold catalyst, AuCl[(o-biPh)((t)Bu)(2)P]Cl/AgNTf(2), improved the regioselectivity, giving the 6-endo adducts in better yields. Furthermore, the hydroamination of alkynyl carbamates bearing an acetal or enone was successfully applied to the concise synthesis of tetracyclic heterocycles such as nitidine via the single catalyst-mediated tandem cyclization which consists of a condensation or a Michael addition of the resulting enecarbamates.
作为 1,2-二氢异喹啉的一种方便直接的合成方法，发展了金（I）催化的（2-炔基）苄基氨基甲酸酯的分子内氢胺化反应。与阳离子金（I）配合物[AuCl(PPh3)/AgNTf2]的反应在室温下进行，得到所需的 6-endo 加合物。添加醇可有效地促进反应，催化剂的用量可减少至 1mol%。然而，带有缺电子芳基或烷基的炔烃主要生成 5-exo 加合物。在这种情况下，使用大位阻的金催化剂，AuCl[(o-biPh)((t)Bu)(2)P]Cl/AgNTf2，可提高区域选择性，以更好的收率得到 6-endo 加合物。此外，通过由缩合或迈克尔加成形成的单催化剂介导的串联环化反应，成功地将带有缩醛或烯酮的炔基氨基甲酸酯的氢胺化应用于诸如 nitidine 的四环杂环的简洁合成。
