Orthogonal Strapping of o‑Haloaryl Ynones with Pyrazolones: A One-Pot, Domino Process toward Spiropyrazolones

A new class of spiroannulated pyrazolone scaffolds have been assembled from diverse o-haloaryl ynones and β-bromoalkenyl ynones via base mediated, one-pot, metal free, orthogonal strapping (tethering) mediated by the recursive anion(s) derived from pyrazolones. These convenient, preparatively useful transformations proceed through either a tandem Michael addition–intramolecular SNAr reaction or a tandem Michael addition–intramolecular AdNE process to furnish a range of pharmacophoric, diverse, spiroannulated pyrazolones from readily accessible precursors.本研究以多样化的邻卤芳基炔酮（o-haloaryl ynones）与β-溴代烯基炔酮（β-bromoalkenyl ynones）为起始底物，通过碱促、无金属一锅法且由吡唑啉酮衍生的递归阴离子介导的正交绑缚（tethering）策略，成功构建了一类全新的螺环化吡唑啉酮（spiroannulated pyrazolone）骨架。该便捷且具备制备应用价值的转化反应可通过两条串联路径完成：一是迈克尔加成-分子内芳香亲核取代（SNAr）串联过程，二是迈克尔加成-分子内AdNE串联过程，最终可从易于获取的前驱体出发，得到一系列结构多样且具有药效团（pharmacophoric）特征的螺环化吡唑啉酮类化合物。