Guranova Natalia, Yakovleva Lyudmila, Bakulina Olga, Dar'in Dmitry, Krasavin Mikhail
Institute of Chemistry, Saint Petersburg State University, 26 Universitetskii Prospect, Peterhof 198504, Russia.
Institute for Medicine and Life Sciences, Immanuel Kant Baltic Federal University, Kaliningrad 236041, Russia.
Molecules. 2022 Oct 25;27(21):7211. doi: 10.3390/molecules27217211.
Based on the previously reported involvement of homophthalic acid monoesters in the Castagnoli-Cushman reaction-type cyclocondensation with imines, we tested a number of other -methyl benzoic acids bearing various electron-withdrawing groups in the α-position. The majority of these substrates delivered the expected tetrahydroisoquinolone adducts on activation with CDI or acetic anhydride. Homophthalic acid mononitriles displayed the highest promise as substrates for the new reaction, both in terms of scope and product yields. Homophthalic acid monoamides either gave low yields or failed to react with imines. Sulfonyl-substituted substrates gave the desired (and hitherto unknown) type of tetrahydroisoquinolines. Despite the low yields, this approach to sulfonyl-substituted tetrahydroisoquinolines appears practical as alternative syntheses based on the traditional, carboxylic acid CCR adducts would presumably be cumbersome and multistep. The azido- and nitro-substituted -methyl benzoic acids failed to react with imines.
基于之前报道的邻苯二甲酸单酯参与与亚胺的卡斯塔尼奥利-库什曼反应型环缩合反应，我们测试了许多其他在α位带有各种吸电子基团的α-甲基苯甲酸。这些底物中的大多数在使用CDI或乙酸酐活化后都生成了预期的四氢异喹啉加合物。邻苯二甲酸单腈作为新反应的底物，在适用范围和产物收率方面都显示出最大的潜力。邻苯二甲酸单酰胺要么产率低，要么无法与亚胺反应。磺酰基取代的底物生成了所需的（且迄今未知的）四氢异喹啉类型。尽管产率较低，但这种合成磺酰基取代四氢异喹啉的方法似乎可行，因为基于传统羧酸CCR加合物的替代合成可能会很繁琐且需要多步反应。叠氮基和硝基取代的α-甲基苯甲酸无法与亚胺反应。
