Department of Organic Chemistry and Technology, Budapest University of Technology and Economics , Budafoki út 8, H-1111 Budapest, Hungary.
J Org Chem. 2018 Feb 16;83(4):2282-2292. doi: 10.1021/acs.joc.7b03176. Epub 2018 Feb 5.
An efficient synthesis has been developed for the preparation of 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones) from readily available anthranilic acid derivatives via a one-pot amide- and pyrrole-formation step, followed by an intramolecular cyclodehydration. The cyclodehydration process is mediated by the activation of aromatic tertiary amides by triflic anhydride (TfO). Comparison of various benzo-substituents is shown to demonstrate the high functional group tolerance of this transformation. In addition, study of the reaction mechanism is also presented to unfold the exact role of the applied base additive. Herein, as a first example, we report our findings that TfO-mediated amide activation is obstructed by the easy protonation of amides by the formed triflic acid during the activation step. Additionally, it has been also proven that the base additive is not involved in the transformation of O-triflyliminium triflates into reactive species (e.g., nitrilium triflates) and is only responsible to neutralize the superacid to avoid the protonation of both the secondary or tertiary amides.
已经开发出一种从易于获得的邻氨基苯甲酸衍生物通过一锅法酰胺和吡咯形成步骤制备 9H-吡咯并[1,2-a]吲哚-9-酮（氟唑酮）的有效合成方法，随后进行分子内环脱水。环脱水过程由三氟甲磺酸酐（TfO）激活芳基叔酰胺介导。比较各种苯取代基表明该转化具有很高的官能团容忍度。此外，还提出了反应机理的研究，以阐明所应用的碱添加剂的确切作用。在这里，作为第一个例子，我们报告了我们的发现，即 TfO 介导的酰胺活化被在活化步骤中由形成的三氟甲磺酸质子化的酰胺的容易质子化所阻碍。此外，还证明碱添加剂不参与 O-三氟甲磺酰亚胺三氟酸盐转化为反应性物质（例如，亚硝酰三氟甲酸盐），并且仅负责中和超强酸以避免仲或叔酰胺的质子化。
