2134/22799 Beatriz Fernandez D.-R. Beatriz Fernandez D.-R. Mark Elsegood Mark Elsegood Gary Fairley Gary Fairley Gareth Pritchard Gareth Pritchard George Weaver George Weaver Pyridone functionalization: regioselective deprotonation of 6-methylpyridin-2(1H)- and -4(1H)-one derivatives Loughborough University 2016 Heterocycles Pyridones Quinolizinones Regioselectivity Metalation Chemical Sciences not elsewhere classified Organic Chemistry 2016-10-12 08:46:28 Journal contribution https://repository.lboro.ac.uk/articles/journal_contribution/Pyridone_functionalization_regioselective_deprotonation_of_6-methylpyridin-2_1H_-_and_-4_1H_-one_derivatives/9389867 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.