Synthesis of cis-/All-cis-Substituted Cyclopropanes through Stereocontrolled Metalation and Pd-Catalyzed Negishi Coupling

We have developed a direct method for the synthesis of cis-substituted cyclopropanes from a cyclopropanecarboxamide through stereocontrolled metalation and Negishi coupling. Under the optimized reaction conditions, various substituents, including di/trisubstituted alkenes and aryl groups, were introduced in a stereoselective manner using a simple amide directing group that could subsequently be converted into an ester. Furthermore, this method was applicable to the synthesis of all- cis-substituted cyclopropanes bearing three different substituents, which are highly congested and strained molecules.