Issue 23, 2022

Practical asymmetric amine nucleophilic approach for the modular construction of protected α-quaternary amino acids

Abstract

We report the first amine nucleophilic approach for the modular construction of enantioenriched protected α-quaternary amino acids. The key to success is the use of an alcohol solvent, which makes a rationally designed COOMe-bonded Cu-allenylidene electrophilic intermediate stable enough to couple with amine nucleophiles before its decomposition. The reaction features wide functional group tolerance with high enantioselectivity, typically >90% ee, and is amenable to the modification of commercially available bioactive molecules. The resultant protected α-amino acids could be readily converted into a number of precious enantioenriched amines featuring α-hindered tertiary carbon centers, which are otherwise synthetically quite challenging, including those of α-amino aldehyde, peptides or α-vinyl amino ester with >92% ee in excellent yields. This protocol could be utilized for the synthesis of the protected bioactive α-ethylnorvaline in 3 steps, a significant advancement in comparison to an 11-step sequence reported previously.

Graphical abstract: Practical asymmetric amine nucleophilic approach for the modular construction of protected α-quaternary amino acids

Supplementary files

Article information

Article type
Edge Article
Submitted
25 apr 2022
Accepted
15 may 2022
First published
05 iyn 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 6806-6812

Practical asymmetric amine nucleophilic approach for the modular construction of protected α-quaternary amino acids

T. Liu, S. Ni and W. Guo, Chem. Sci., 2022, 13, 6806 DOI: 10.1039/D2SC02318K

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