Substrate‐Controlled Regiodivergent Annulation for Construction of Highly Substituted Cyclopropanes

ABSTRACT A mild, regio‐ and stereoselective synthesis of a series of highly substituted cyclopropanes was accomplished via mono‐ and bis(2 + 1) cycloaddition reactions of α,β,γ,δ‐ unsaturated carbonyl compounds with α‐halomalonates. The reactions proceeded in good yields (up to 90% yields), displaying excellent regio‐ and diastereoselectivity (up to > 25:1 dr). The resulting products which obtained as single stereoisomers, possess two contiguous stereocenters including a quaternary carbon center in monocyclopropanation or four contiguous stereocenters bearing three quaternary carbon center in dicyclopropanation, from readily accessible starting materials using simple operational procedures. Additionally, the novel polysubstituted cyclopropanes exhibit potential anticancer activity, as evidenced by a molecular docking study. The structural framework and relative configuration of the products were determined through spectroscopic techniques as well as single‐crystal X‐ray diffraction analysis.