Solvent-Controlled Regioselective [3 + 2] Reactions from Benzofuran-Derived Azadienes and N,N'-Cyclic Azomethine Imines: Synthesis of Two Different Benzofuran Spiro-Fused Bicyclic Pyrazolidine Frameworks.

We report a catalyst-free, regioselective [3 + 2] cycloaddition reaction between benzofuran-derived azadienes (BDAs) and N,N'-cyclic azomethine imines, where regioselectivity is controlled by modulating solvent polarity. Spiro[benzofuran-2,2'-pyrazolo[1,2-a]pyrazole] is obtained in high yields (up to 93%) using acetonitrile as the solvent, while the novel spiro[benzofuran-2,1'-pyrazolo[1,2-a]pyrazole] forms in moderate to good yields (42%-73%) with carbon tetrachloride. This solvent-controlled protocol exhibits excellent diastereoselectivity (dr >20:1) for both products, along with a broad substrate scope. Furthermore, scale-up experiments and derivatization studies have been successfully performed. This protocol provides an efficient strategy for regioselective control in the diversified synthesis of bicyclic pyrazolidines, offering a new approach for constructing bicyclic pyrazolidines with different configurations.