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An atom economical method for the preparation of variously substituted 4H-pyrrolo[2,3-d]oxazoles was developed on the basis of thermal isomerization of 5-(2H-azirin-2-yl)oxazoles. The latter were prepared by Rh2(oct)4 catalyzed reaction of 2-(3-aryl/heteroaryl)-2-diazoacetyl-2H-azirines with a set of substituted acetonitriles, benzonitriles, acrylonitrile and fumaronitrile. According to DFT calculations the transformation of 5-(2H-azirin-2-yl)oxazole to 4H-pyrrolo[2,3-d]oxazole occurs through the nitrenoid-like transition state to give a 3aH-pyrrolo[2,3-d]oxazole intermediate, followed by 1,5-H-shift. [ABSTRACT FROM AUTHOR]

Azirinyl-substituted conjugated ynones were first synthesized by the reaction of lithiated acetylenes with 2 H -azirine-2-carbonyl chlorides. Azirinyl ethynyl ketones containing only a C(O)C≡CR substituent at position 2 of the azirine ring are good precursors for obtaining α-C(O)C≡CR substituted NH-pyrroles and 5-[C(O)C≡CR]-substituted NH-imidazoles, reacting selectively only at the azirine moiety with 1,3-diketones and arylamidines, respectively. Various N-heterocyclic hybrids (pyrrole-pyrimidine, imidazole-pyrimidine, pyrrole-isoxazole, imidazole-isoxazole, pyrimidine-pyrrole-thiophene, pyrrole-pyrimidine-thiophene, imidazole-pyrimidine-thiophene, isoxazole-pyrrole-thiophene) have been prepared based on orthogonal or domino reactions of an azirine and C(O)C≡CR moieties of azirinyl ethynyl ketones.

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.

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.