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Issue 32, 2020

Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation

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Abstract

Pyridines are ubiquitous aromatic rings used in organic chemistry and are crucial elements of the drug discovery process. Herein we describe a new catalytic method that directly introduces a methyl group onto the aromatic ring; this new reaction is related to hydrogen borrowing, and is notable for its use of the feedstock chemicals methanol and formaldehyde as the key reagents. Conceptually, the C-3/5 methylation of pyridines was accomplished by exploiting the interface between aromatic and non-aromatic compounds, and this allows an oscillating reactivity pattern to emerge whereby normally electrophilic aromatic compounds become nucleophilic in the reaction after activation by reduction. Thus, a set of C-4 functionalised pyridines can be mono or doubly methylated at the C-3/5 positions.

Graphical abstract: Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation

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Article information


Submitted
14 May 2020
Accepted
29 Jul 2020
First published
10 Aug 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 8595-8599
Article type
Edge Article

Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation

A. Grozavu, H. B. Hepburn, E. P. Bailey, P. J. Lindsay-Scott and T. J. Donohoe, Chem. Sci., 2020, 11, 8595 DOI: 10.1039/D0SC02759F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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