Article Synopsis
- This research explores how donor-acceptor cyclopropanes can be transformed to create complex molecules efficiently, overcoming challenges in forming chiral quaternary centers.
- The study introduces a novel palladium-catalyzed cycloaddition method that achieves high diastereoselectivity and enantioselectivity using vinyl cyclopropanes with two different electron-withdrawing groups.
- Key findings indicate that remote stereoinduction via hydrogen bonding from chiral ligands plays a crucial role in the reaction's success, leading to the synthesis of various chiral five-membered heterocycles with impressive yields and stereoselectivity.
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Article Abstract
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.
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