Highly Diastereo‐ and Regioselective Synthesis of Spiropyrazole‐Cyclopropanes via All‐Carbon (2 + 1) Annulations of Acyclic Conjugated Imines With 4‐Halo Pyrazolones

ABSTRACT A straightforward, diastereo‐ and regioselective synthesis of spiro‐cyclopropane‐pyrazolone compounds was achieved via all‐carbon (2 + 1) cycloaddition reactions between acyclic conjugated imines and 4‐halo pyrazolones. The reactions proceeded with moderate to high yields (up to 92% yields), and displayed outstanding regio‐ and diastereoselectivity (in all cases > 25:1 dr). As a result, the desired spirocyclic compounds, which incorporate both a pyrazolone and a cyclopropane moiety, were obtained as single diastereoisomers. Additionally, the spiropyrazole‐cyclopropanes which possess three contiguous stereocenters including a quaternary carbon center, have demonstrated potential ALDH1A1 inhibitor, as substantiated by a molecular docking study. The structure and relative configuration of the product were unambiguously determined by single‐crystal x‐ray diffraction analysis.