Chemoselective Copper(l)-Catalyzed 1,2-Reduction of Conjugated Amides by a Molecular Recognition Strategy
- 1Institute of Chemistry, Faculty of Natural Sciences, Technische Universität Chemnitz, Straße der Nationen 62, Chemnitz, 09111
Abstract
The selective 1,2-reduction of conjugated amides represents an elusive transformation, owing to the intrinsically low reactivity of the amide group and competing conjugate reduction. Here, we report an unprecedented copper(I)-catalyzed hydrogenation of conjugated amides that selectively furnishes allylic alcohols using molecular hydrogen as the terminal reductant. A bifunctional copper catalyst exploits molecular recognition of a privileged amide motif to enable reduction of the amide functionality while preserving the conjugated alkene, thereby reversing the chemoselectivity commonly associated with copper hydride catalysis. The method provides access to a range of aromatic, heteroaromatic, aliphatic, and conformationally restricted allylic alcohols and tolerates additional reducible functionalities. Mechanistic studies reveal a decisive interplay between base-mediated E/Z isomerization and selective recognition and hydrogenation of the E-configured substrate. Moreover, isolation of a conjugated aldehyde intermediate supports a stepwise pathway involving amide reduction, C–N bond cleavage, and subsequent aldehyde hydrogenation. These results establish molecular recognition as a strategy to unlock otherwise inaccessible chemoselectivity in catalytic hydrogenation.
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BibTeX
@misc{voigtlander2026chemoselective,
title = {{Chemoselective Copper(l)-Catalyzed 1,2-Reduction of Conjugated Amides by a Molecular Recognition Strategy}},
author = {Maximilian Voigtländer and Nikola Broftová and Anne Krenkel and Dimitrios-Ioannis Tzaras and Florian P. Schulz and Johannes F. Teichert},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010861/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010861/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Chemoselective Copper(l)-Catalyzed 1,2-Reduction of Conjugated Amides by a Molecular Recognition Strategy
AU - Maximilian Voigtländer
AU - Nikola Broftová
AU - Anne Krenkel
AU - Dimitrios-Ioannis Tzaras
AU - Florian P. Schulz
AU - Johannes F. Teichert
PY - 2026
DA - 2026/10/22
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010861/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010861/v1
AB - The selective 1,2-reduction of conjugated amides represents an elusive transformation, owing to the intrinsically low reactivity of the amide group and competing conjugate reduction. Here, we report an unprecedented copper(I)-catalyzed hydrogenation of conjugated amides that selectively furnishes allylic alcohols using molecular hydrogen as the terminal reductant. A bifunctional copper catalyst exploits molecular recognition of a privileged amide motif to enable reduction of the amide functionality while preserving the conjugated alkene, thereby reversing the chemoselectivity commonly associated with copper hydride catalysis. The method provides access to a range of aromatic, heteroaromatic, aliphatic, and conformationally restricted allylic alcohols and tolerates additional reducible functionalities. Mechanistic studies reveal a decisive interplay between base-mediated E/Z isomerization and selective recognition and hydrogenation of the E-configured substrate. Moreover, isolation of a conjugated aldehyde intermediate supports a stepwise pathway involving amide reduction, C–N bond cleavage, and subsequent aldehyde hydrogenation. These results establish molecular recognition as a strategy to unlock otherwise inaccessible chemoselectivity in catalytic hydrogenation.
ER -