Diastereoselective Synthesis of Highly Substituted Methylene Cyclobutanes by Pd Catalysis

Methylene cyclobutanes are valuable yet synthetically challenging motifs due to the strain and stereochemical complexity of the cyclobutane ring. Herein, we report a chemo‐ and diastereoselective palladium‐catalyzed intramolecular coupling/cyclization of borylated 1,5‐dienes with iodoarenes to afford highly substituted methylene cyclobutanes. The transformation displays broad substrate scope and remarkable functional group tolerance, including free amines and alcohols. Both aryl‐ and alkyl‐substituted borylated 1,5‐dienes are compatible, and the reaction proceeds with complete diastereocontrol. The methodology is fully enantiospecific when an enantioenriched borylated 1,5‐diene is employed, with no erosion of chiral information observed. Downstream functionalizations of the methylene cyclobutane products demonstrate their synthetic versatility and underscore the potential of this strategy for accessing structurally complex and cyclobutane derivatives.