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. Spirobenzofuran-2,2'-pyrazolo[1,2-apyrazole] is obtained in high yields (up to 93%) using acetonitrile as the solvent, while the novel spirobenzofuran-2,1'-pyrazolo[1,2-apyrazole] 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.
Wang et al. (Sun,) studied this question.