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Pyridone functionalization: regioselective deprotonation of 6-methylpyridin-2(1H)- and -4(1H)-one derivatives

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posted on 12.10.2016, 08:46 by Beatriz Fernandez D.-R., Mark ElsegoodMark Elsegood, Gary Fairley, Gareth PritchardGareth Pritchard, George WeaverGeorge Weaver
Selective functionalization at the α-methyl group of 1-substituted pyridin-2(1H)- and 4(1H)-ones (2- and 4-pyridones) can be achieved by appropriate choice of base. n-Butyllithium was found to effect clean 6(2)-methyl deprotonation of 1-benzyl-2- and -4-pyridone derivatives, while potassium hexamethyldisilazide (KHMDS) was the preferred reagent for methyl deprotonation of the corresponding 1-methyl-2- and -4-pyridones. Deprotonation proceeds smoothly at –78 °C, and the resulting anions react readily with a wide range of electrophiles (aldehydes, ketones, alkylating reagents, and an azo compound) under precise temperature control to form usefully functionalized 2- and 4-pyridones and quinolizinones.

Funding

We thank AstraZeneca and Loughborough University for financial support, and the Engineering and Physical Sciences Research Council (EPSRC) UK National Mass Spectrometry Facility at Swansea for mass spectra.

History

School

  • Science

Department

  • Chemistry

Published in

European Journal of Organic Chemistry

Citation

FERNANDEZ D.-R., B. ... et al, 2016. Pyridone functionalization: regioselective deprotonation of 6-methylpyridin-2(1H)- and -4(1H)-one derivatives. European Journal of Organic Chemistry, 2016(31), pp. 5238–5242.

Publisher

© Wiley-VCH Verlag

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Acceptance date

16/09/2016

Publication date

2016

Notes

This is the peer reviewed version of the following article: FERNANDEZ D.-R., B. ... et al, 2016. Pyridone functionalization: regioselective deprotonation of 6-methylpyridin-2(1H)- and -4(1H)-one derivatives. European Journal of Organic Chemistry, 2016(31), pp. 5238–5242., which has been published in final form at http://dx.doi.org/10.1002/ejoc.201601156. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

ISSN

1434-193X

eISSN

1099-0690

Language

en