Pedrosa R, Andrés C, Iglesias J M, Pérez-Encabo A
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Valladolid, Dr. Mergelina s/n, 47011-Valladolid, Spain.
J Am Chem Soc. 2001 Mar 7;123(9):1817-21. doi: 10.1021/ja002864q.
Aryllithiums prepared by bromine-lithium interchange in chiral 2-(o-bromophenyl)-substituted perhydro-1,3-benzoxazines participate in the intramolecular 6-exo carbolithiation reaction with unactivated double bonds attached to the nitrogen substituent of the heterocycle. When the reaction time is extended or no TMEDA is used, the cyclized lithium intermediates react intramolecularly with the N,O-acetal system leading to 2-azabenzonorbornane derivatives. The reactions are highly stereoselective and constitute a high-yielding synthesis of enantiopure 4-substituted tetrahydroisoquinolines or 7-substituted 2-azabenzonorbornanes.
在手性2-(邻溴苯基)取代的全氢-1,3-苯并恶嗪中通过溴-锂交换制备的芳基锂与连接在杂环氮取代基上的未活化双键发生分子内6-外向碳锂化反应。当反应时间延长或不使用TMEDA时，环化的锂中间体与N,O-缩醛体系发生分子内反应，生成2-氮杂降冰片烷衍生物。这些反应具有高度的立体选择性，构成了对映体纯的4-取代四氢异喹啉或7-取代2-氮杂降冰片烷的高产率合成方法。
