Direct copper-catalysed deaminative cyanation of aliphatic primary amines
- 1State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China
- 2Department of Chemistry, Yonsei University, Seoul, Republic of Korea
- 3Department of Chemistry, University of Chicago, Chicago, IL, USA
Abstract
The cyano group is a versatile motif in medicinal chemistry, serving as both a target and a precursor to other functional groups. However, direct deaminative cyanation of aliphatic amines remains a challenge due to the inertness of C–N bonds and the instability of amines under oxidative conditions. Here we report a catalytic, direct deaminative cyanation of aliphatic primary amines without preactivation. This method employs an anomeric amide for radical generation from amines and TMSCN as the cyano source, with a copper catalyst and N-fluorosulfonamide reagent cooperatively facilitating both radical coupling and propagation. This work integrates anomeric amide activation with transition-metal-catalysed bond formation. The strategy enables not only efficient cyanation but also asymmetric deaminative cyanation, stereocentre inversion and downstream transformations such as homologation and CO insertion, providing versatile tools for amine diversification. Direct deaminative cyanation of aliphatic amines is hampered by inert C–N bonds and oxidative instability. Now a copper-catalysed, preactivation-free approach enabled by anomeric amide activation is reported that also includes an asymmetric variant.
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BibTeX
@article{xue2026direct,
title = {{Direct copper-catalysed deaminative cyanation of aliphatic primary amines}},
author = {Jiang‐Hao Xue and Shuang Lin and J Huang and Taeseok Kang and Bumsu Park and Mark D. Levin and Myojeong Kim and Honggen Wang},
journal = {Nature Catalysis},
year = {2026},
month = jul,
doi = {10.1038/s41929-026-01578-9},
url = {https://doi.org/10.1038/s41929-026-01578-9},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Direct copper-catalysed deaminative cyanation of aliphatic primary amines
AU - Jiang‐Hao Xue
AU - Shuang Lin
AU - J Huang
AU - Taeseok Kang
AU - Bumsu Park
AU - Mark D. Levin
AU - Myojeong Kim
AU - Honggen Wang
PY - 2026
DA - 2026/07/10
JO - Nature Catalysis
DO - 10.1038/s41929-026-01578-9
UR - https://doi.org/10.1038/s41929-026-01578-9
AB - The cyano group is a versatile motif in medicinal chemistry, serving as both a target and a precursor to other functional groups. However, direct deaminative cyanation of aliphatic amines remains a challenge due to the inertness of C–N bonds and the instability of amines under oxidative conditions. Here we report a catalytic, direct deaminative cyanation of aliphatic primary amines without preactivation. This method employs an anomeric amide for radical generation from amines and TMSCN as the cyano source, with a copper catalyst and N-fluorosulfonamide reagent cooperatively facilitating both radical coupling and propagation. This work integrates anomeric amide activation with transition-metal-catalysed bond formation. The strategy enables not only efficient cyanation but also asymmetric deaminative cyanation, stereocentre inversion and downstream transformations such as homologation and CO insertion, providing versatile tools for amine diversification. Direct deaminative cyanation of aliphatic amines is hampered by inert C–N bonds and oxidative instability. Now a copper-catalysed, preactivation-free approach enabled by anomeric amide activation is reported that also includes an asymmetric variant.
SN - 2520-1158
ER -