Issue 46, 2021

Radical chain monoalkylation of pyridines


The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and no external oxidant is required. A rate constant for the addition of a primary radical to N-methoxylepidinium >107 M−1 s−1 was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radicals to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction has been used for the preparation of unique pyridinylated terpenoids and was extended to a three-component carbopyridinylation of electron-rich alkenes including enol esters, enol ethers and enamides.

Graphical abstract: Radical chain monoalkylation of pyridines

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Article information

Article type
Edge Article
20 May 2021
21 Oct 2021
First published
03 Nov 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 15362-15373

Radical chain monoalkylation of pyridines

S. Rieder, C. Meléndez, F. Dénès, H. Jangra, K. Mulliri, H. Zipse and P. Renaud, Chem. Sci., 2021, 12, 15362 DOI: 10.1039/D1SC02748D

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