A new synthesis of β-keto amides by reduction of Passerini adducts

Synthesis and antimycobacterial activity of new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives

“…[22,24] The starting compounds, BFX, were obtained by previously described methods. [18,25] Compound 1 was commercially available whereas the rest of the β-ketoamides were synthesized as follows: compound 2 was synthesized by Passerini reaction between the appropriate glyoxal and isocyanide [26]; compound 3 was synthesized by condensation of the corresponding ester and the appropriate aryl amine. [27] Compounds 4-9 were obtained through the acetoacetylation of corresponding aryl amines by diketene.…”

Reductive Passerini/Tsuji–Trost Strategy towards β,γ-Unsaturated Amides

“…For other α,β-unsaturated aldehydes and isocyanides, some aldehyde still remained unreacted in the mixture even after two days of reaction (Table 1, entries 2-9). The resulting allylic formates 2a-i were next treated with a catalytical amount of Pd(PPh 3 ) 4 in warm THF, a classical condition for Tsuji-Trost-type allylation. 6 Except for amide 2d, which gave a complex mixture of isomers, all amides were cleanly converted within less than 30 minutes at 50°C to the reduced amides 3a-i (Table 2) formed as a single regioisomer.…”

“…Taking into account the deleterious effect of residual isocyanide on the activity of Pd(PPh 3 ) 4 , we decided to modify the procedure. The first step was performed in toluene (toluene and CH 2 Cl 2 give similar yields of 2a from cinnamaldehyde) adding a slight excess of formic acid.…”

Zinc Ammonium Chloride

“…6 (G) b-Keto acyloxyamides are readily transformed into the corresponding b-keto amides by reductive deacetoxylation in extraordinarily mild conditions, using activated zinc metal in a mixture of saturated aqueous ammonium chloride and methanol. 7 (H) Habashita et al 8 described a convenient and efficient method for the synthesis of synthetically useful non-racemic allylic alcohols from 4-methylbenzenesulfonates of non-racemic 2,3-epoxy alcohols by reaction with potassium iodide followed by zinc powder and ammonium chloride in a one-pot manner.…”