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‐...

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Published in:Angewandte Chemie International Edition 2023-01, Vol.62 (3), p.e202212444-n/a
Main Authors: Xiao, Yu‐Qing, Li, Miao‐Miao, Zhou, Zheng‐Xin, Li, Yu‐Jie, Cao, Meng‐Yue, Liu, Xiao‐Peng, Lu, Hai‐Hua, Rao, Li, Lu, Liang‐Qiu, Beauchemin, André M., Xiao, Wen‐Jing
Format: Article
Language:English
Subjects:
Asymmetric Cycloaddition
Catalysis
Cycloaddition
Cycloaddition Reaction
Cyclopropane
Cyclopropanes - chemistry
D-A Cyclopropane
Enantiomers
H-Bonding
Hydrogen bonds
Organic compounds
Palladium
Palladium - chemistry
Palladium Catalysis
Quaternary Stereocenters
Stereoisomerism
Stereoselectivity
Substrates
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Summary: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. Two palladium‐catalyzed asymmetric (3+2) cycloadditions of donor‐acceptor (D‐A) cyclopropenes bearing two different electron‐withdrawing groups were reported. Various chiral five‐membered oxa‐ and aza‐heterocycles were produced, and good yields and high stereoselectivities were obtained. The key to the success of this reaction is the remote stereoinduction through H‐bonding from chiral ligands.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202212444