Ring lithiation of pyridones

Abstract

Lithiation of 1 -methyl-2-pyridone takes place mainly at the methyl group which then leads to a dimer (11) by addition to a second mol equivalent of pyridone at C-6. Lithiation of 1 -methyl-4-pyridone takes place cleanly and efficiently at C-2; this lithio derivative gave a dimer (13) with a second mol equivalent of the pyridone and reacted with a variety of carbon electrophiles to produce 2-substituted 4-pyridones (14c-n).1 -Methoxymethyl-, 1 -benzyloxymethyl-, and 1 -(2-trimethylsilylethoxy)methyl-4-pyridones also lithiate at C-2, though these lithio derivatives were much less reactive towards electrop h i les. * This paper had not been abstracted by Chemical Abstracts up to the end of Volume 103, 1985. We thank Professor Katritzky for calling our attention to this paper after the publication of our preliminary communication. 24

Stabilities of uracil and pyridone-based carbanions: a systematic study in the gas phase and solution and implications for the mechanism of orotidine-5′-monophosphate decarboxylase

“…Unfortunately this approach is found to be impractical due to the preferential deprotonation of the methyl group in pyridone 5 . 22 If carbanion 7 or 8 or 9 is a strong enough base, it will deprotonate the indicator weak acid (In–H) and produce a colored carbanion (In − ) as a conjugate base as shown in Equation 3. The bracketing between the strongest acid that yielded a color change and the weakest acid that that did not yield a color change gives estimates of the p K a values.…”

Recent Progress in Selective Additions of Organometal Reagents to Carbonyl Compounds

“…For those compounds, common allylation reagents such as allylmagnesium chloride are ineffective even with a large excess of reagent. In contrast, 6-allyl products (23) are selectively obtained from N-Me-protected substrates without forming a self-adduct byproduct via generating an initial anion at the N-Me group [20]. Interestingly, 4-allyl products (24) are obtained with perfect regioselectivities via a Cope rearrangement after 6-allylations with (allyl)Bu 2 MgLi.…”

Carbanions from decarboxylation of orotate analogs: Stability and mechanistic implications

“…The pK a of DMSO is 35 so that protonation of the carbanions by the solvent is not an issue [17]. The reported preferential deprotonation of the methyl groups in pyridone 5 makes it impractical to generate carbanions 7-9 through the deprotonation of compounds 4-6 by a strong base such as butyllithium [19].…”