Enantioselective Palladium-Catalyzed α-Arylation of Acyclic Esters
Jianxun Huang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032 China
Both authors contributed equally to this work.
Search for more papers by this authorDr. Chao Pei
Chemical & Analytical Development, Suzhou Novartis Technical Development Co., Ltd, Changshu, Jiangsu, 215537 China
Both authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Prof. Dr. He Yang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Dr. Bin Wu
Chemical & Analytical Development, Suzhou Novartis Technical Development Co., Ltd, Changshu, Jiangsu, 215537 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Dr. Wenjun Tang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032 China
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, 310024 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorJianxun Huang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032 China
Both authors contributed equally to this work.
Search for more papers by this authorDr. Chao Pei
Chemical & Analytical Development, Suzhou Novartis Technical Development Co., Ltd, Changshu, Jiangsu, 215537 China
Both authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Prof. Dr. He Yang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Dr. Bin Wu
Chemical & Analytical Development, Suzhou Novartis Technical Development Co., Ltd, Changshu, Jiangsu, 215537 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Dr. Wenjun Tang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032 China
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, 310024 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorGraphical Abstract
A Pd-catalyzed enantioselective α-arylation of α,α-disubstituted esters with aryl bromides is established for the first time by employing P-chiral monophosphorus ligand 3-Pent-BIDIME as a chiral ligand, leading to a series of enantioenriched α,α-diaryl esters possessing quaternary carbon stereocenters in moderate to good yields and high enantioselectivities. The method features a broad substrate scope, mild conditions, excellent functional group compatibility, and low Pd loadings (as low as 1 mol%). Its synthetic utilities are exemplified by the efficient preparation of a chiral α,α-diaryl substituted γ-lactone and the asymmetric synthesis of (R)-amolanone.
Abstract
A Pd-catalyzed enantioselective α-arylation of α,α-disubstituted esters with aryl bromides is established for the first time by employing P-chiral monophosphorus ligand 3-Pent-BIDIME as a chiral ligand, leading to a series of enantioenriched α,α-diaryl esters possessing quaternary carbon stereocenters in moderate to good yields and high enantioselectivities. The method features a broad substrate scope, mild conditions, excellent functional group compatibility, and low Pd loadings (as low as 1 mol%). The synthetic power of this protocol is exemplified by the efficient preparation of a chiral α,α-diaryl substituted γ-lactone and asymmetric synthesis of (R)-amolanone. DFT calculation revealed an NaBr-bridged downstream transmetallation and the importance of noncovalent interaction in controlling the enantioselectivity.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
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| anie202505458-sup-0001-SuppMat.pdf16 MB | Supporting Information |
| anie202505458-sup-0002-SuppMat.cif552.2 KB | Supporting Information |
| anie202505458-sup-0003-SuppMat.cif2.5 MB | Supporting Information |
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