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Issue 24, 2016

C2-Alkenylation of N-heteroaromatic compounds via Brønsted acid catalysis

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Abstract

Substituted heteroaromatic compounds, especially those based on pyridine, hold a privileged position within drug discovery and medicinal chemistry. However, functionalisation of the C2 position of 6-membered heteroarenes is challenging because of (a) the difficulties of installing a halogen at this site and (b) the instability of C2 heteroaryl-metal reagents. Here we show that C2-alkenylated heteroaromatics can be accessed by simple Brønsted acid catalysed union of diverse heteroarene N-oxides with alkenes. The approach is notable because (a) it is operationally simple, (b) the Brønsted acid catalyst is cheap, non-toxic and sustainable, (c) the N-oxide activator disappears during the reaction, and (d) water is the sole stoichiometric byproduct of the process. The new protocol offers orthogonal functional group tolerance to metal-catalysed methods and can be integrated easily into synthetic sequences to provide polyfunctionalised targets. In broader terms, this study demonstrates how classical organic reactivity can still be used to provide solutions to contemporary synthetic challenges that might otherwise be approached using transition metal catalysis.

Graphical abstract: C2-Alkenylation of N-heteroaromatic compounds via Brønsted acid catalysis

  • This article is part of the themed collection: New Talent

Supplementary files

Article information


Submitted
04 Apr 2016
Accepted
21 Apr 2016
First published
03 May 2016

This article is Open Access

Org. Biomol. Chem., 2016,14, 5820-5825
Article type
Paper

C2-Alkenylation of N-heteroaromatic compounds via Brønsted acid catalysis

G. E. M. Crisenza, E. M. Dauncey and J. F. Bower, Org. Biomol. Chem., 2016, 14, 5820 DOI: 10.1039/C6OB00705H

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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