Polyfunctional fluoroalkyl-containing carbonyl compounds in the synthesis of heterocycles

Efficient procedures for the regioselective synthesis of fluoroalkyl-containing threefive-, six-, and seven-membered heterocycles as well as of related fused compounds, namely, α,β-epoxyketones, α,β-aziridinylketones, pyrazoles, pyrazolines, isoxazolines, 1,2-dithiolenes, amino- and mercaptopyrimidines, Δ^3,5-2-thioxo-1,3,2-thiazaphosphorines, Δ^3,5-2-thioxo-1,3,2-oxazaphosphorines, 2,3-dihydro-1,4-diazepines, azirino[1,2-a]quinoxalines, benzo[b]-and naphtho[2,3-b]-1,4-diazepines, and triazolopyridazines, which have been developed by the authors and coworkers, are summarized. The α- and β-functionalized fluoroalkylcontaining carbonyl compounds (β-diketones, β-ketoesters, their salts, regioisomeric β-aminovinyl ketones, β-aminovinylthiones, β-hydroxyketones, α,β-enones, and their halogen derivatives) were used as synthons in the processes of formation of the above-mentioned heterocycles. Dedicated to the memory of Academician I. Ya. Postovskii on his 100th birthday. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1279–1286, July, 1998.     

Iron(III) chloride-catalyzed convenient one-pot synthesis of β-acetamido carbonyl compounds

A one-pot multi-component reaction of aldehydes, enolizable ketones or 1,3-dicarbonyls, acetonitrile/benzonitrile, and acetyl chloride is described for the preparation of β-acetamido carbonyl compounds using FeCl₃·6H₂O as a mild, inexpensive, and highly efficient catalyst. The effect of substrate as well as substituent for multi-component reaction versus Knoevenagel condensation is also illustrated. The key features of this methodology are operational simplicity, mild reaction conditions, and good yields.     

Iron(III) triflate-catalyzed one-pot synthesis of acetal-type protected cyanohydrins from carbonyl compounds

A variety of cyanohydrin THP ethers were readily prepared from carbonyl compounds with trimethylsilyl cyanide and tetrahydropyran-2-yl acetate under the influence of a catalytic amount of iron(III) triflate in a convenient one-pot procedure. This method was also effective to prepare O-protected cyanohydrins by various acetal-type protective groups.     

NbCl5-Catalyzed one-pot Mannich-type reaction: three component synthesis of β-amino carbonyl compounds

Three-component Mannich-type reaction of acetophenone, aromatic aldehydes and aromatic amines was catalyzed by NbCl₅ at ambient temperature to give various β-amino ketones in high yields.     

One-pot synthesis of nitrogen heterocycles initiated by regio- and diastereoselective carbon-carbon bond formation of bifunctional carbonyl compounds

We report a one-pot synthesis of nitrogen heterocyclic compounds initiated by the allylation of the formyl group of bifunctional carbonyl compounds accompanying chemo-, regio-, and diastereoselective carbon-carbon bond formation in side chain moieties.     

An expedient one-pot sequential five-component synthesis of highly substituted spiro-pyrrolidine heterocycles

An expedient one-pot sequential five-component synthesis of highly substituted pyrrolidine heterocycles involving [3+2]-cycloaddition of azomethine ylides as the key step is described. The protocol provides a mild reaction condition, high yield of the products, high regioselectivity and operational simplicity to assemble complex structural entity in a single operation. The structure of the product was confirmed by spectroscopic and single crystal X-ray analysis.     

Substituent-controlled domino-Knoevenagel-hetero Diels-Alder reaction—a one-pot synthesis of polycyclic heterocycles

The reaction of 2-(N-alkenyl-N-aryl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde with dimedone/Meldrum’s acid/4-hydroxycoumarin by heating in ethanol in the presence of pyridine produces polycyclic heterocycles bearing pyridine and pyran rings in a one-pot reaction. The effect of substituents on N-atom of the amino function controls the mode of reaction. Terminal alkenes prefer intramolecular Michael type reaction, but non-terminal alkenes favour Diels-Alder reaction, whereas, under similar condition, 2-(N-alkyl-N-allyl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde undergoes domino-Knoevenagel-hetero Diels-Alder reaction.     

Bismuth(III) chloride-catalyzed one-pot Mannich reaction: three-component synthesis of β-amino carbonyl compounds

A simple and efficient method has been developed for the one-pot Mannich reaction of β-amino carbonyl compounds from aromatic aldehydes, aromatic ketones and aromatic amines in the presence of a catalytic amount of bismuth trichloride.     

Direct one-pot synthesis of alpha-siloxy-Weinreb amides from aldehydes

A one-pot method for synthesizing alpha-siloxy-Weinreb amides from aldehydes was developed with use of N,O-dimethylhydroxylamine and a masked acyl cyanide reagent bearing a tert-butyldimethylsilyl group avoiding the competitive reaction toward N-methoxy-N-methyl-2-amino-1-siloxymalononitrile.     

Cyanoamino compounds in synthesis syntheses of some heterocycles

Transformations of some heterocyclic cyanoamino compounds leading to various heterocyclic systems are described.s-Triazolo (1,5-α)azines are obtained either in a direct synthetic approach or via the substituted aminotetrazoles, substituted 3-amino-5-oxo-1,2,4-oxadiazolines, and fromN-ethoxycarbonylN′-heteroaryl thioureas orN-heteroarylN′-hydroxyguanidine. The cyanoamino group reacts also witho-difunctional benzenes to give the corresponding substituted derivatives of benzimidazole, benzoxazole or benzothiazole.     

Metal promoted synthesis of heterocycles from heteroacyclic compounds

New synthetic methods, based upon metal mediated or catalyzed C-C/C-O/C-N bond formation, for heterocycles and their application to natural product syntheis are described.     

Reactions of isocyanatophosphoryl difluoride with π-abundant nitrogen heterocycles and carbonyl compounds

Reactions of electron-rich nitrogen heterocycles with isocyanatophosphoryl difluoride were studied. Novel heteroylaminophosphoryl difluorides were obtained in high yields. N-Phosphorylated imines were synthesized for the first time from carbonyl compounds and phosphorus isocyanates. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 564–566, March, 2006.     

A one-pot method for the synthesis of 2-aminobenzimidazoles and related heterocycles

A rapid and efficient one-pot method for the synthesis of 2-aminobenzimidazoles and related heterocycles is described. The reaction is mediated by a polymer-supported carbodiimide, which simplifies product isolation. The scope and limitations of this method are described.     

An efficient and facile one-pot synthesis of cyanohydrin esters from carbonyl compounds catalyzed by iron(III) chloride

A variety of cyanohydrin esters were readily prepared from carbonyl compounds with trimethylsilyl cyanide and acid anhydride under the influence of a catalytic amount of iron(III) chloride in a convenient one-pot procedure.     

Enone synthesis via α-pyridylseleno carbonyl compounds

Oxidative elimination of α-pyridylseleno carbonyl compounds affords enones in excellent yields, providing an improved method for dehydrogenation of ketones and aldehydes. These results indicate that pyridylseleno group is a better leaving group than phenylseleno group in selenoxide elimination leading to enones.