Taming Chiral Quaternary Stereocenters via Remote H‐Bonding Stereoinduction in Palladium‐Catalyzed (3+2) Cycloadditions

Ring-opening transformations of donor-acceptor (D-A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D-A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99 % yields, 99 : 1 er and >19 : 1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.