Synthesis of isoquinolines and pyridines by the palladium- and copper-catalyzed coupling and cyclization of terminal acetylenes
Synthesis of isoquinolines and pyridines by the palladium- and copper-catalyzed coupling and cyclization of terminal acetylenes
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DOI：
10.1021/ol990067v
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发表时间：
1999-08-26
期刊：
影响因子：
5.2
通讯作者：
Larock, RC
中科院分区：
文献类型：
--
作者：
Roesch, KR;Larock, RC
在钯催化剂存在下，芳基和烯基取代的末端乙炔与邻碘苯甲醛的叔丁亚胺偶联，合成了3-取代异喹啉。烷基取代的乙炔不经历这种环化过程。然而，这些钯催化反应生成的含有芳基、烯基和烷基取代基的中间体亚氨基炔在铜催化下进行环化反应，产率高，反应时间短。因此，在钯催化剂的存在下，芳基、烯基和烷基取代的末端乙炔与邻碘苯甲醛或3-卤代-5-烯醛的叔丁亚胺偶联，然后在铜催化下亚氨基炔的环化反应，一锅法合成了异喹啉和吡啶。采用钯催化的偶联/环合方法，经过7步反应，总收率为20%，完成了异喹啉天然产物狄肯苯碱B的全合成。
[GRAPHICS]3-Substituted isoquinolines have been synthesized by the coupling of aryl and alkenyl-substituted terminal acetylenes with the tert-butylimine of o-iodobenzaldehyde in the presence of a palladium catalyst. Alkyl-substituted acetylenes fail to undergo this annulation process. However, the intermediate iminoalkynes containing aryl, alkenyl, and alkyl substituents produced from these palladium-catalyzed reactions undergo copper-catalyzed cyclization in excellent yields and short reaction times. Isoquinolines and pyridines have thus been prepared in a one-pot synthesis via coupling of aryl-, alkenyl-, and alkyl-substituted terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes or 3-halo-5-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of the resulting iminoalkynes. The total synthesis of the isoquinoline natural product decumbenine B has been accomplished in seven steps and 20% overall yield by employing this palladium-catalyzed coupling/cyclization methodology.