Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
Chem Asian J. 2012 Feb 6;7(2):306-13. doi: 10.1002/asia.201100834. Epub 2011 Dec 16.
A convenient method for the synthesis of highly substituted isoquinolines and isoquinolinium salts by the nickel-catalyzed cyclization of ortho-haloketoximes and -ketimines, respectively, with alkynes is described. The reaction of ortho-haloketoximes and various alkynes in the presence of [Ni(PPh(3))(2)Br(2)] and zinc powder in a mixture of acetonitrile and tetrahydrofuran at 80 °C for 15 hours gave 1,3,4-trisubstituted isoquinoline products in moderate to excellent yields and high regioselectivity. The corresponding isoquinoline N-oxide was found to be the intermediate in the cyclization reaction pathway. In contrast, the reaction of ortho-haloketimines and alkynes under similar catalytic conditions in tetrahydrofuran at 70 °C for two hours gave 1,2,3,4-tetrasubstituted isoquinolinium salts in good to excellent yields.
描述了一种方便的方法，通过镍催化的邻卤代酮肟和酮亚胺分别与炔烃的环化反应，合成高度取代的异喹啉和异喹啉鎓盐。在乙腈和四氢呋喃的混合物中，在[Ni(PPh3)2Br2]和锌粉的存在下，邻卤代酮肟和各种炔烃于 80°C 反应 15 小时，以中等至优异的收率和高区域选择性得到 1,3,4-三取代异喹啉产物。发现相应的异喹啉 N-氧化物是环化反应途径中的中间体。相比之下，在类似的催化条件下，邻卤代酮亚胺和炔烃在四氢呋喃中于 70°C 反应 2 小时，以良好至优异的收率得到 1,2,3,4-四取代异喹啉鎓盐。
