Pyridone Functionalization: Regioselective Deprotonation of 6-Methylpyridin-2(1H)- and-4(1H)-one Derivatives

作者：Ropero Beatriz P Fernandez Diaz; Elsegood Mark R J^*; Fairley Gary; Pritchard Gareth J^*; Weaver George W^*

来源：European Journal of Organic Chemistry, 2016, 2016(31): 5238-5242.

DOI：10.1002/ejoc.201601156

• Heterocycles
• Pyridones
• Quinolizinones
• Regioselectivity
• Metalation

Selective functionalization at the a-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 degrees 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.

• 出版日期2016-11