Low-Energy Photocatalysis Platform for Direct Regiospecific α-C(sp3)ꟷH Alkynylation of Tertiary Amines
Abstract
Propargylamines constitute a valuable class of α-alkynyl amines that are widely encountered in medicinal chemistry and chemical biology. Herein, we report a regiospecific α-C(sp3)–H alkynylation of tertiary amines that enables the direct synthesis of propargylamines from unactivated tertiary amines and terminal alkynes. The transformation proceeds under mild, base-free conditions using sustainable low-energy photon irradiation and is initiated by single-electron-transfer (SET) activation of the tertiary amine, generating a reactive iminium intermediate that undergoes nucleophilic coupling with a transient Cu(I)–acetylide species. The protocol accommodates a diverse range of tertiary amines and terminal alkynes, including bioactive molecules and pharmaceuticals, providing access to structurally diverse internal alkynes and versatile click-ready terminal alkynes with excellent functional-group tolerance. The synthetic utility of the method is further demonstrated through gramscale reactions, while comprehensive mechanistic investigations provide insights into the photoredox and copper catalytic pathways underlying this transformation.
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BibTeX
@misc{lal2026lowenergy,
title = {{Low-Energy Photocatalysis Platform for Direct Regiospecific α-C(sp3)ꟷH Alkynylation of Tertiary Amines}},
author = {Nand Lal and Rahul D. Thombare and Puja Singh and Aslam C. Shaikh},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008513/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008513/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Low-Energy Photocatalysis Platform for Direct Regiospecific α-C(sp3)ꟷH Alkynylation of Tertiary Amines
AU - Nand Lal
AU - Rahul D. Thombare
AU - Puja Singh
AU - Aslam C. Shaikh
PY - 2026
DA - 2026/09/08
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008513/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008513/v1
AB - Propargylamines constitute a valuable class of α-alkynyl amines that are widely encountered in medicinal chemistry and chemical biology. Herein, we report a regiospecific α-C(sp3)–H alkynylation of tertiary amines that enables the direct synthesis of propargylamines from unactivated tertiary amines and terminal alkynes. The transformation proceeds under mild, base-free conditions using sustainable low-energy photon irradiation and is initiated by single-electron-transfer (SET) activation of the tertiary amine, generating a reactive iminium intermediate that undergoes nucleophilic coupling with a transient Cu(I)–acetylide species. The protocol accommodates a diverse range of tertiary amines and terminal alkynes, including bioactive molecules and pharmaceuticals, providing access to structurally diverse internal alkynes and versatile click-ready terminal alkynes with excellent functional-group tolerance. The synthetic utility of the method is further demonstrated through gramscale reactions, while comprehensive mechanistic investigations provide insights into the photoredox and copper catalytic pathways underlying this transformation.
ER -