Stereodivergent access to non-natural α-amino acids via enantio- and Z / E -selective catalysis

The precise control of Z and E configurations of the carbon-carbon double bond in alkene synthesis has long been a fundamental challenge in synthetic chemistry, even more pronounced when simultaneously striving to achieve enantioselectivity [( Z , R ), ( Z , S ), ( E , R ), ( E , S )]. Moreover, ena...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2024-08, Vol.385 (6712), p.972-979
Main Authors: Li, Panpan, Zheng, En, Li, Guanlin, Luo, Yicong, Huo, Xiaohong, Ma, Shengming, Zhang, Wanbin
Format: Article
Language:English
Subjects:
Amino acids
Carbon
Catalysis
Catalysts
Chemical bonds
Chemical synthesis
Configurations
Enantiomers
Palladium
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Summary:The precise control of Z and E configurations of the carbon-carbon double bond in alkene synthesis has long been a fundamental challenge in synthetic chemistry, even more pronounced when simultaneously striving to achieve enantioselectivity [( Z , R ), ( Z , S ), ( E , R ), ( E , S )]. Moreover, enantiopure non-natural α-amino acids are highly sought after in organic and medicinal chemistry. In this study, we report a ligand-controlled stereodivergent synthesis of non-natural α-quaternary amino acids bearing trisubstituted alkene moieties in high yields with excellent enantioselectivity and Z / E selectivities. This success is achieved through a palladium/copper–cocatalyzed three-component assembly of readily available aryl iodides, allenes, and aldimine esters by simply tuning the chiral ligands of the palladium and copper catalysts. Editor’s summary Adaptable control over the disposition of groups at each end of a carbon-carbon double bond remains a challenge in chemical synthesis. In the E configuration, the largest groups are diagonally opposed, whereas in the Z configuration, they’re on the same side. Li et al . paired up copper and palladium catalysts to deliver either E - or Z -configured double bonds in unnatural amino acids, depending on the ligand choice. The reaction is also highly enantioselective at the quaternary alpha carbon stereocenter. —Jake S. Yeston
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.ado4936