Synthesis of N-Alkylpyridin-4-ones and Thiazolo[3,2-a]pyridin-5-ones Through Pummerer-Type Reactions

Abstract

N-alkylated 4-pyridones were obtained through a one-pot procedure involving either normal or interrupted Pummerer reactions between triflic anhydride activated sulfoxides and 4-fluoropyridine derivatives, followed by hydrolysis. On the other hand, triflic anhydride activated benzyl 6-fluoro-2-pyridyl sulfoxide could react with alkenes or alkynes to afford thiazolo[3,2-a]pyridin-5-ones, via the pyridinium salt intermediates.

Synthesis of N-Alkylpyridin-4-ones and Thiazolo[3,2-a]pyridin-5-ones through Pummerer-Type Reactions

“…18a−e As part of our research program 19a−h on the reactivity of activated sulfoxides, 20−30 we herein report an alternative Pummerer-type reaction approach to access either N-alkylpyridin-4-one or thiazolo [3,2-a]pyridin-5-one structures from readily available pyridine derivatives. 31…”

“…Pyridones are an important class of heterocyclic compounds. − For example, a number of N -alkylpyridin-4-one or thiazolo­[3,2- a ]­pyridin-5-one structures were reported to have interesting pharmaceutical activities. − For the synthesis of N -alkylpyridin-4-one, alkylation of the parent 4-pyridone, or its tautomeric form 4-hydroxypyridine, would afford a mixture of N-/O-alkylation products, − namely, the N-alkylated 4-pyridones or 4-alkoxypyridines. Thus, traditional approach to N-alkylated 4-pyridones usually involves the condensation between pyran-4-one and amines, , oxidation of piperidin-4-one, alkylation of pyridin-4-one, − as well as other cyclization reactions. − On the other hand, reports on the synthesis of thiazolo­[3,2- a ]­pyridin-5-one structures almost always involve the cyclization reactions to construct the pyridone rings. − As part of our research program − on the reactivity of activated sulfoxides, − we herein report an alternative Pummerer-type reaction approach to access either N -alkylpyridin-4-one or thiazolo­[3,2- a ]­pyridin-5-one structures from readily available pyridine derivatives …”