Clive Derrick L J, Peng Jianbiao, Fletcher Stephen P, Ziffle Vincent E, Wingert David
Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
J Org Chem. 2008 Mar 21;73(6):2330-44. doi: 10.1021/jo7026307. Epub 2008 Feb 16.
2,3-Dihydroindoles, 1,2,3,4-tetrahydroquinolines, and 2,3,4,5-tetrahydrobenzo[b]azepines are available by a process that represents formal radical cyclization onto aromatic rings. Optically pure benzo-fused heterocycles are also accessible by this method. p-Iodophenols, especially those with the phenolic oxygen protected as a MOM-ether, can be coupled with amino alcohols to produce N-aryl amino alcohols, which can be converted into the corresponding alkyl iodides in which the nitrogen is protected as a carbamate. These compounds give cross-conjugated ketones after removal of the phenolic protecting group and oxidation with PhI(OAc)(2) in the presence of MeOH. The ketones undergo 5-, 6- or 7-exo-trigonal radical cyclization, and then exposure to acid, or sequential treatment with a Grignard reagent and then acid, effects rearomatization to produce the benzo-fused nitrogen heterocycles.
2,3-二氢吲哚、1,2,3,4-四氢喹啉和2,3,4,5-四氢苯并[b]氮杂䓬可通过一种在芳环上进行形式上的自由基环化反应的方法来制备。光学纯的苯并稠合杂环也可通过该方法获得。对碘苯酚，特别是那些酚羟基被保护为甲氧基甲基醚的对碘苯酚，可与氨基醇偶联生成N-芳基氨基醇，后者可转化为相应的烷基碘化物，其中氮被保护为氨基甲酸酯。在除去酚羟基保护基并在甲醇存在下用PhI(OAc)₂氧化后，这些化合物生成交叉共轭酮。这些酮进行5-、6-或7-外向三角自由基环化反应，然后用酸处理，或先用格氏试剂处理再用酸处理，实现芳构化，生成苯并稠合含氮杂环。
