Orthogonal Strapping of <i>o</i>‑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）为原料，通过碱介导、无金属一锅法，借助吡唑啉酮衍生的递归阴离子实现正交绑缚（tethering），成功构建了一类全新的螺环化吡唑啉酮（spiroannulated pyrazolone）骨架。 这类便捷且具备制备应用价值的转化反应，可通过串联迈克尔加成-分子内亲核芳香取代（SNAr）过程，或是串联迈克尔加成-分子内AdNE过程进行，从易得的前体出发，合成一系列兼具药效团特性与结构多样性的螺环化吡唑啉酮类化合物。