Unnatural α-amino acid synthesis enabled by nickel-catalysed enantioselective hydrocarbamoylation of enamides via C‒H functionalisation
- 1Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark
Abstract
Enantioselective construction of unnatural α-amino acids is highly desirable due to their widespread applications across biochemistry, medicinal industry and materials science. Herein, we report a straightforward and efficient method for the assembly of structurally diverse enantioenriched α-amino acid derivatives from readily accessible enamides and N,N-dimethylformamide (DMF) by merging nickel hydride catalysis and hydrogen atom transfer (HAT). The protocol affords good yields and high enantioselectivities of products which easily can be converted into unprotected unnatural α-amino acids and other valuable chiral building blocks. Notably, the enantiopurity of the products can be further enhanced by normal flash chromatography on silica gel, providing a practical platform for enantiopurification of both oily and solid products. This radical cross-coupling reaction proceeds under mild conditions, tolerates a broad range of functional groups and is amenable to the construction of enantioenriched α-amino amides bearing active pharmaceutical ingredients on the sidechain.
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BibTeX
@article{chen2026unnatural,
title = {{Unnatural α-amino acid synthesis enabled by nickel-catalysed enantioselective hydrocarbamoylation of enamides via C‒H functionalisation}},
author = {Xuemeng Chen and Søren Kramer},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77983-2},
url = {https://doi.org/10.1038/s41467-026-77983-2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Unnatural α-amino acid synthesis enabled by nickel-catalysed enantioselective hydrocarbamoylation of enamides via C‒H functionalisation
AU - Xuemeng Chen
AU - Søren Kramer
PY - 2026
DA - 2026/09/24
JO - Nature Communications
DO - 10.1038/s41467-026-77983-2
UR - https://doi.org/10.1038/s41467-026-77983-2
AB - Enantioselective construction of unnatural α-amino acids is highly desirable due to their widespread applications across biochemistry, medicinal industry and materials science. Herein, we report a straightforward and efficient method for the assembly of structurally diverse enantioenriched α-amino acid derivatives from readily accessible enamides and N,N-dimethylformamide (DMF) by merging nickel hydride catalysis and hydrogen atom transfer (HAT). The protocol affords good yields and high enantioselectivities of products which easily can be converted into unprotected unnatural α-amino acids and other valuable chiral building blocks. Notably, the enantiopurity of the products can be further enhanced by normal flash chromatography on silica gel, providing a practical platform for enantiopurification of both oily and solid products. This radical cross-coupling reaction proceeds under mild conditions, tolerates a broad range of functional groups and is amenable to the construction of enantioenriched α-amino amides bearing active pharmaceutical ingredients on the sidechain.
SN - 2041-1723
ER -