2-Cyano-6-(trifluoromethyl)-4H-pyran-4-one: A novel versatile CF3-containing building block

A novel, two-step synthesis of 4-pyridone-3-carboxamides from 2-cyano-4-pyrones

“…c o m / l o c a t e / t e t l e t substrate, which is able to react with different nucleophiles with or without affecting the pyrone ring. 6 We found that 2a reacted easily with both aliphatic and aromatic amines in ethanol at À20°C over 2 days to produce CF 3 -containing 5-amino-3-oxopent-4-enamides 4a-f in yields of 28-78%. The first step of the reaction leading to 4 presumably involves attack of the NH 2 group at C-6 of 2a with concomitant opening of the pyrone ring to give intermediate A, which is a reactive acyl cyanide.…”

“…10 5-Amino-3-oxo-4-enamides 4 belong to a poorly explored class of polyfunctional compounds, the chemical properties of which have still not been investigated (besides acid hydrolysis to 4-hydroxy-2-pyridones 6,9 ). In connection with this, we examined the reactivity of carbamoylated aminoenones 4 to construct biologically interesting CF 3 -containing 4-pyridone-3-carboxamides as well as non-fluorinated pyridones.…”

“…3 In this Letter, we report a novel synthesis of 4-pyridone-3-carboxamides from 5-amino-3-oxopent-4-enamides, which in turn were prepared from the corresponding 2-cyano-4-pyrones. We previously found 6 that dehydration of 4-oxo-6-(trifluoromethyl)-4H-pyran-2-carboxamide (1a) 7 with trifluoroacetic anhydride in the presence of pyridine at 0°C led to the formation of 2-cyano-6-(trifluoromethyl)-4-pyrone (2a) in 61% yield. We now report the synthesis of 2-cyano-4-pyrone (2b) and 2-cyano-6-methyl-4-pyrone (2c) from the corresponding 4-pyrone-2-carboxamides 1b,c under the same conditions, in 48% 8 and 55% yields, respectively (it proved important to carry out the reaction at À10°C).…”

“…The less reactive 2-cyano-6-methyl-4-pyrone (2c) reacted under the same conditions only with benzylamine, over 3 weeks, to produce compound 4i in 50% yield, which has been previously obtained from triacetic acid lactone (3c) and benzylamine 9 (Scheme 1 and Table 1). Thus, 2-cyano-4-pyrones 2 can be considered as synthetic equivalents of 4-hydroxy-2-pyrones 3, of which 4-hydroxy-6-(trifluoromethyl)-2-pyrone (3a) and 4-hydroxy-6-methyl-2-pyrone (3c) are known compounds.10 5-Amino-3-oxo-4-enamides 4 belong to a poorly explored class of polyfunctional compounds, the chemical properties of which have still not been investigated (besides acid hydrolysis to 4-hydroxy-2-pyridones 6,9 ). In connection with this, we examined the reactivity of carbamoylated aminoenones 4 to construct biologically interesting CF 3 -containing 4-pyridone-3-carboxamides as well as non-fluorinated pyridones.…”

2-(Trifluoromethyl)-4H-pyran-4-ones: Convenient, available and versatile building-blocks for regioselective syntheses of trifluoromethylated organic compounds

“…on the basis of 2-CF 3 -4-pyrones using convenient methods leads to the conclusion that these cyclic enones can be widely used as excellent starting substrates in biological or medicinal chemistry and related areas. Highly electrophlilic 2-cyano-6-CF 3 -4-pyrone, synthesis of which was described in 2012 [11], is one of the most advanced and versatile CF 3 -containing buildingblocks [11,12], due to both the presence of four available for nucleophilic attack reactive positions in the molecule of this pyrone and a possible substitution of the cyano group [11,12].…”