Lanzhou team vinylates N-methyl C–H bonds of trialkylamines with photoredox/cobalt catalysis
A laboratory method from the Chinese Academy of Sciences selectively modifies the N-methyl group of tertiary amines with alkynes, including in drug molecules, without directing groups.
Researchers at the State Key Laboratory of Low Carbon Catalysis and Carbon Dioxide Utilization, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, together with colleagues from the University of Chinese Academy of Sciences and East China University of Science and Technology, have described a method for N-methyl-selective α-C–H vinylation of unactivated tertiary alkylamines with internal alkynes. The work was published on 6 November 2026 in Nature Communications; the corresponding author is Ji-Bao Xia nature.com
Nature Communicationsnature.comOpen source ↗. The reaction yields trisubstituted allylic amines.
The selectivity problem in trialkylamines
Late-stage functionalization of drugs that contain trialkylamines offers a direct route to new chemical space. However, unactivated trialkylamines carry several competing α-amino C–H bonds, which makes selective modification difficult. The authors address this with a dual photoredox/cobalt catalytic system.
The method is redox-neutral and needs neither directing groups nor external oxidants. According to the authors, it proceeds under mild conditions with high regioselectivity, stereoselectivity and site-selectivity. Mechanistic experiments and computational studies support a pathway in which photoredox catalysis generates an α-amino carbon radical, followed by aminomethyl-cobalt(I)-mediated migratory insertion of the alkyne and protonolysis.
Scope and applications
The reaction accommodates diverse amines and alkynes, including electronically unbiased dialkyl alkynes nature.com
Nature Communicationsnature.comOpen source ↗. The authors demonstrated gram-scale synthesis and prepared the fungicide fenpropidin by this route. They also applied the method to late-stage functionalization of structurally complex pharmaceuticals.
Some of the resulting drug analogues showed enhanced apparent binding affinity for the human histamine H1 receptor, the authors report. This is a measurement of receptor binding for modified compounds, not a result on therapeutic effect.
The authors present the approach as a practical strategy for selective editing of trialkylamines and for late-stage diversification of such molecules. The study describes a synthetic method; the reported products were obtained and characterized in the laboratory.
