Augusto C. Veronese

Tin (IV) Chloride-promoted Synthesis of 4-Aminopyridines and 4-Aminoquinolines

Abstract Ortho-aminobenzonitriles 1 react with β-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to give 4-aminoquinolines 2 and 4-amino-2-quinolones 3 respectively. Similarly β-enaminonitriles 7 afford 4-aminopyridines 8 and 4-amino-2-pyridones 9.

Metal-catalysed carbon—carbon bond formation in the reaction of β-dicarbonyls with nitriles

Abstract A new synthetic procedure to carbon—carbon bond formation between CH acidic compounds and nucleophiles, like Michael acceptors and nitriles, is based on the use of metal(II) centres as catalysts in a homogeneous phase. The contributions to the inorganic, organic and mechanistic aspects of the reaction of β-dicarbonyls with nitriles are reviewed. Metal catalysis appears, for the investigated systems, largely superior to the traditional approach, which employs organic bases as catalysts, and the perspectives of an extension of this metal-catalysed procedure are illustrated.

A facile synthesis of pyrazole, isoxazole and pyrimidine ortho-dicarboxylic acid derivatives via β-enaminoketoesters

Abstract β-Alkoxycarbonyl-β-enaminoketoesters 1a,b react with hydrazines to give pyrazole ortho -dicarboxylic acid derivatives 3, 4 and 5 . Similarly 1a reacts with hydroxylamine to give isoxazole 6 and with amidines and guanidine to give pyrimidine ortho -dicarboxylic acid monoesters 7a-c . The total or partial hydrolysis of selected heterocycles afforded the dicarboxylic acids 8, 9 and 10 and the dicarboxylic acid monoesters 11 and 12 .

Tin (IV) chloride-promoted reactions of β-dicarbonyl compounds with nitriles. Synthesis of aminopyridines and aminoquinolines.

Abstract β-Ketoesters and β-diesters react with β-enaminonitriles in the presence of stoichiometric amounts of tin (IV) chloride to give 4-aminopyridines and pyridones while they react with aromatic orthoaminonitriles to give 4-aminoquinolines and quinolones.

A new simple route for the synthesis of (±)-2-azetidinones starting from β-enaminoketoesters

Abstract β-Enaminoketoesters 1, obtained through metal-catalysed reaction of methyl acetoacetate with alkyl cyanoformates have been conveniently transformed into β-aminoesters 4, 5 by reduction of both the carbonyl group and the carbon–carbon double bond of the enaminoester moiety. These intermediates could be easily converted to (±)-2-azetidinones 6, 7 structurally related to thienamycin in good yield and high diastereoselectivity.

Cyclocondensations of DMF with α-haloamides, an aziridinone, or a Δ2-1,2,3-triazolin-5-one

The formation of oxazolidin-4-one derivatives from DMf and 2-bromo-isobutyramides (3a,b), the aziridinone 4a, or the 1,2,3-triazolin-5-one 5a, is reported. The possibility that a common dipolar intermediate cycloadds onto the carbonyl group of DMF, is considered.

A new route to the synthesis of pyrazole and pyrimidine C-nucleoside derivatives

Abstract A new route to the synthesis of pyrazole and pyrimidine C-nucleosides, which involves as the key step a metal promoted reaction of β-D-ribofuranosyl ketoesters with alkyl cyanoformates is described. 2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl cyanide 1 reacts with α-bromoesters, in the presence of zinc dust, to give β-D-ribofuranosyl-enaminoesters 2 which are hydrolysed with 1N hydrochloric acid to β-ketoesters 3. The reactions of β-ketoesters 3 with alkyl cyanoformates, in the presence of tin(IV) chloride or of catalytic amounts of metal acetylacetonates, afford β-D-ribofuranosyl enaminoketoesters 4. These compounds react with benzylhydrazine and acetamidine to give pyrazole and pyrimidine C-nucleosides (6,7).

A new and efficient route to the synthesis of pyrazole and pyrimidine C-nucleoside derivatives

Abstract A new route to the synthesis of pyrazole and pyrimidine C-nucleosides, involving as the key step a metal catalysed reaction of β-D-ribofuranosyl ketoesters with alkyl cyanoformates, is described, 2,3,5-Tri-O-benzoyl-β-D-ribofuranosyl cyanide (1) reacts with α-bromoesters, in the presence of zinc dust, to give β-D-ribofuranosyl-enaminoesters 2 which are easily hydrolised to β-ketoesters 3. The reactions of compounds 3 with alkyl cyanoformates, in the presence of catalytic amounts of [Cu(acac)2], afford C-glycosyl enaminoketosters 4. These compounds react with benzylhydrazine and acetamidine to give pyrazole and pyrimidine C-nucleosides 5 and 6 respectively.

Reactions of β-dicarbonyl compounds with acyl cyanides catalyzed or promoted by metal centres in the homogeneous phase

The C–C bond-forming reaction between β-dicarbonyl compounds and acyl cyanides is catalyzed by nickel acetylacetonate or promoted by tin tetrachloride. Thus, β-diketones react with acyl cyanides in the presence of catalytic amounts of [Ni(acac)2] to give β-enamino diketones 3. β-Enamino keto esters 8 or β-enamino diesters 9 are obtained in the reactions of methyl acetoacetate or methyl malonate with acyl cyanides in the presence of stoichiometric amounts of SnCl4. The reactions of acyl cyanides with methyl malonate also afford furanone derivatives 10, whose structure has been determined, in one case, by a single-crystal X-ray analysis. β-Keto amides react with acyl cyanides to give pyrrolidine derivatives 13 both under catalytic conditions and stoichiometric conditions where an equimolar equivalent of promoter was used.

A new simple route for the synthesis of (±)-2-azetidinones starting from β-Enaminoketoesters

Abstract β-Enaminoketoesters, obtained by metal-catalyzed reaction between alkyl acetoacetates and alkyl cyanoformates, are useful starting materials for rapid access to β-acetyl-dehydroaspartic acid derivatives which could be transformed into (±)-2-azetidinones bearing a 1-hydroxy-ethyl substituent through suitable reductive processes.