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2-(1H-Pyrazol-1-ylcarbonyl)-2H-azirines were synthesized by in situ trapping of 2H-azirine-2-carbonyl chlorides, generated by Fe(II)-catalyzed isomerization of 5-chloroisoxazoles, with pyrazoles. According to DFT calculations, the selectivity of nucleophilic substitution at the carbonyl group of 2H-azirine-2-carbonyl chloride by a pyrazole nucleophile, which is a mixture of two tautomers, is controlled by thermodynamic factors. 2-(1H-Pyrazol-1-ylcarbonyl)-2H-azirines are excellent precursors for the preparation of two other pyrazole-nitrogen heterocycle dyads: 5-(1H-pyrazol-1-yl)oxazoles by photolysis and 1-(1H-pyrrol-2-ylcarbonyl)-1H-pyrazoles by a Ni(II)-catalyzed reaction with 1,3-dicarbonyl compounds. 5-(1H-Pyrazol-1-yl)oxazoles show strong emission in acetonitrile at 360-410 nm with high quantum yields. [ABSTRACT FROM AUTHOR]

The first synthesis of pyrroles by Fe(II)-catalyzed isomerization of 4-vinylisoxazoles is reported. 5-Alkoxy, amino, and N,N-dialkylamino-3-aryl/alkyl-4-(2-R-vinyl)isoxazoles afford 2-aryl/alkyl-5-aryl/alkyl/methoxycarbonyl-1H-pyrrol-3-carboxylic acid derivatives typically under mild conditions with cheap and available FeCl2·4H2O as a catalyst. The isomerization of 5-alkoxy/amino-3-arylisoxazoles, bearing unsaturated carbo and heterocyclic substituents at the position 4, gives the corresponding fused pyrrolecarboxylic acid derivatives in high yields. DFT calculations were used to elucidate a probable mechanism of the isomerization and explain the influence of steric congestion of the vinyl moiety on the isomerization pathway. [ABSTRACT FROM AUTHOR]

A high yield synthesis of fluorescent benzo, thieno, and furo [c]-fused methyl 7-aryl-6H-pyrrolo[3,4-c]pyridazine-5-carboxylates, including unprecedented heterocyclic skeletons, was performed by the transformation of methyl 4-aminopyrrole-2-carboxylate into the corresponding diazo compound, followed by intramolecular azo coupling under acid conditions onto a nucleophilic aryl or hetaryl group in the 3-position. Azo coupling is completely regioselective and, according to DFT calculations, a kinetically controlled reaction. N-Methylation of 1,3-disubstituted 2H-pyrrolo[3,4-c]cinnolines occurs selectively at N5 under kinetic control, leading exclusively to 5-methyl-5H-pyrrolo[3,4-c]cinnoline derivatives. [ABSTRACT FROM AUTHOR]

A diazo approach toward functionalized naphtho[1,2- d ]imidazole derivatives has been developed. It involved a new reaction of arylamidines with 2-(α-diazoacyl)-2 H -azirines giving 5-aryl-4-(α-diazoacyl)-1 H -imidazoles under mild conditions in good yields. The mechanism of annulation of azirines with amidines is discussed based on DFT calculations. The reaction proceeds in an unusual manner by cleavage of the azirine C-C bond, allowing for the transfer of the aryl substituent from the arylamidine to the proper position of the key intermediate of naphtho[1,2- d ]imidazole synthesis. Under thermolysis conditions, 5-aryl-4-(α-diazoacyl)-1 H -imidazoles undergo Wolff rearrangement followed by the selective 6π-cyclization of transient ketene to form 3 H -naphtho[1,2- d ]imidazoles bearing various substituents in the positions 2,3,4,5,7,8,9. Additionally, variation of the substituents at position 5 of naphtho[1,2- d ]imidazoles is possible through the formation of triflates and subsequent cross-coupling reactions. One more heterocyclic pharmacophoric skeleton, 3 H -furo[3',2':3,4]naphtho[1,2- d ]imidazole, was easily constructed from methyl 5-hydroxy-3 H -naphtho[1,2- d ]imidazole-4-carboxylates in a one-pot mode using O-alkylation with phenacyl bromides followed by base-induced intramolecular acyl substitution at room temperature with high yields.

A divergent diazo approach toward alkyl 5/4-hydroxy-3 H -benzo[ e ]indole-4/5-carboxylates has been developed. The reaction of 1,3-diketones with alkyl 2-diazo-3-oxo-3-(2 H -azirin-2-yl)propanoates catalyzed by Co(acac) 3 or Ni(acac) 2 gives various alkyl 3-(1 H -pyrrol-2-yl)-2-diazo-3-oxopropanoate in good yields. The latter undergo Wolff rearrangement followed by the 6π-cyclization of transient ketene to form alkyl 5-hydroxy-3 H -benzo[ e ]indole-4-carboxylates bearing various substituents in positions 1, 2, 7, and 8, as well as derivatives of methyl 4-hydroxy-6 H -thieno[2,3- e ]indole-5-carboxylates and methyl 5-hydroxy-7 H -benzo[ c ]carbazole-6-carboxylate under thermolysis or Rh 2 (OAc) 4 catalysis. Isomeric benzoindoles, alkyl 4-hydroxy-3 H -benzo[ e ]indole-5-carboxylates, have been prepared by Boc-protection of the pyrrole nitrogen of alkyl 3-(1 H -pyrrol-2-yl)-2-diazo-3-oxopropanoates followed by an intramolecular formal carbene insertion into the aromatic C-H bond catalyzed by Cu(OTf) 2 . The hydroxyl group of alkyl 5/4-hydroxy-3 H -benzo[ e ]indole-4/5-carboxylates, through the formation of the corresponding triflates, allows the introduction of various substituents into the 5/4 position of benzo[ e ]indoles using the cross-coupling reaction and even form a new heterocyclic backbone, benzo[ k ]pyrrolo[2,3- i ]phenanthridine, via a tandem Suzuki reaction/nucleophilic acyl substitution.

A diazo strategy for the intramolecular azirine ring expansion was developed. Azirinyl-substituted diazodicarbonyl compounds, prepared from diazoacetylazirines, were converted in excellent yields to 2-hydroxy-3-oxo-2,3-dihydro-1 H -pyrrole-2-carboxylates under Rh catalysis in the presence of water. According to DFT calculations, the formation of only pyrrolinone derivatives and the absence of O-H insertion products of Rh carbene into water are due to the low Gibbs free energy of the transition state for the concerted opening of the azirine ring and recyclization to pyrrolone in intermediate Rh complexes.

α-Diazopyrroles selectively react with enamines at room temperature to give either (4+2)-cycloaddition-dehydroamination cascade products, pyrrolo[2,1- c ][1,2,4]triazines, or azo coupling products. The reaction was used for the synthesis of functionalized ortho -fused heterocycles with new tetrahydrobenzo[ e ]pyrrolo[2,1- c ][1,2,4]triazine and tetrahydro-6 H -cyclohepta[ e ]pyrrolo[2,1- c ][1,2,4]triazine frameworks. Unstable azo compounds, 2-[(2-aminovinyl)diazenyl]pyrroles, were obtained from enamines of tetralone or acyclic ketones. According to the density functional theory calculations, (4+2)-cycloaddition of α-diazopyrroles with enamines proceeds in a nonconcerted manner via the zwitterionic intermediate, which undergoes cyclization to pyrrolotriazine or a competitive 1,5-prototropic shift leading to the formation of azo coupling product.

The synthesis of 5-aryl- and 4-aryl/hetaryl/cyclopropyl/alkynyl-5-aryl-1 H -pyrrole-2,3-diones by formal isomerization of isoxazole-5-carbaldehydes mediated Mo(CO) 6 in wet MeCN has been developed. The resulting 1 H -pyrrole-2,3-diones are good precursors for substituted 1 H -pyrrolo[2,3- b ]quinoxalines.

A four-step quasi one-pot procedure for the preparation of fully substituted nicotinates from ketone enamines and 4-methylideneisoxazol-5-ones has been developed. The reaction sequence involves (1) reaction of 4-methylideneisoxazol-5-ones with ketone enamines with the formation of isoxazole-5-ols, (2) their O-methylation with diazomethane, (3) hydrogenative cleavage of the O-N bond in 5-methoxyisoxazoles under action of Mo(CO) 6 /H 2 O and simultaneous isomerization and condensation of the formed enamines, with the formation of dihydropyridines, and (4) aromatization of the latter.

The reaction conditions for the Buchner reaction of 2-(diazoacetyl)-2 H -azirines with benzene leading to 2-(cyclohepta-2,4,6-trien-1-yl)-2 H -azirines have been found. The azirine fragment of these compounds was subsequently used to prepare 5-(cyclohepta-2,4,6-trien-1-yl)isoxazoles and α-(cyclohepta-2,4,6-triene-1-ylcarbonyl)-1 H -pyrroles. NMR and DFT calculations showed that the cycloheptatriene-norcaradiene valence isomerization in the corresponding moieties of synthesized azirines, isoxazoles, and pyrroles is very fast at room temperature. Cycloheptatriene valence isomer predominates in azirines and pyrroles, while 5-(cycloheptatrienyl)isoxazoles exist in a pure cycloheptatriene form at 25 °C in chloroform solution. In accordance with the X-ray analysis, two of the synthesized pyrroles crystallized as norcaradiene isomers from a solution of equilibrium mixture of valence isomers. Reductive isoxazole ring opening using the Mo(CO) 6 /H 2 O reductive system afforded ( Z )-3-amino-3-aryl-1-(cyclohepta-2,4,6-trien-1-yl)prop-2-en-1-ones, which are pure cycloheptatriene isomers. α-(Cycloheptatrieneylcarbonyl)-1 H -pyrroles were transformed into the α-(benzylcarbonyl)-1 H -pyrroles under cooperative TFA/Rh 2 (TFA) 4 catalysis.

A flexible method was developed for the synthesis of 2,2'-bi-, 2,2':6',2″-ter-, and 2,2':6',2'':6'',2‴-quaterpyridines containing a nicotinic acid moiety. The approach involves the Fe(II)/Au(I)-catalyzed rearrangement of key 4-propargylisoxazole building blocks bearing a pyrid-2-yl or quinolin-2-yl substituent at the 3-position and Pd(0)-catalyzed cross-coupling reactions.

The Co(III)-catalyzed reaction of 1,3-dicarbonyl compounds with 2-(diazoacetyl)-2 H -azirines, prepared by a simplified procedure from 2 H -azirin-2-carbonyl chlorides, led in high yields to the formation of 2-(diazoacetyl)pyrroles, while leaving the diazoacetyl function intact. The intramolecular aromatic substitution reaction of 2-(diazoacetyl)pyrroles, catalyzed by Cu(OTf) 2 , provided selectively previously unknown benzo[ e ]- and hetero[ e ]-fused indol-7-oles in good yields. Formylation of benzo[ e ]indol-4-ol led selectively to the 5-formyl derivative, which is a good precursor for an unusual salen ligand and its Ni-complex. Triflates prepared from benzo[ e ]indol-4-oles gave various 4-substituted benzo[ e ]indoles carrying aryl, 2-thienyl, 2-pyridyl, and alkynyl groups, in excellent yields using cross-coupling reactions. 4-(2-Pyridyl)benzo[ e ]indoles, upon treatment with BF 3 ·Et 2 O/Et 3 N, afforded a new type of fluorescent boron complexes with large Stokes shifts.