Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles.

In the presence of copper sulfate, three- or four-component reactions of 2-methylindole, aromatic aldehydes and various cyclic dienophiles in refluxing toluene afforded diverse spirotetrahydrocarbazoles. This reaction is an important development of the Levy reaction by using 2-methylindole to replace ethyl indole-2-acetate and successfully provides facile access to important polysubstituted spiro[carbazole-3,3'-indolines], spiro[carbazole-2,3'-indolines], spiro[carbazole-3,5'-pyrimidines] and spiro[carbazole-3,1'-cycloalkanes] in satisfactory yields and with high diastereoselectivity.

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels-Alder reaction.

The p-TsOH-catalyzed Diels-Alder reaction of 3-(indol-3-yl)maleimides with chalcone in toluene at 60 °C afforded two diastereoisomers of tetrahydropyrrolo[3,4-c]carbazoles, which can be dehydrogenated by DDQ oxidation in acetonitrile at room temperature to give the aromatized pyrrolo[3,4-c]carbazoles in high yields. On the other hand, the one-pot reaction of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones with chalcones or benzylideneacetone in acetonitrile in the presence of p-TsOH and DDQ resulted in polyfunctionalized carbazoles in satisfactory yields. The reaction mechanism included the DDQ oxidative dehydrogenation of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones to the corresponding 3-vinylindoles, their acid-catalyzed Diels-Alder reaction and sequential aromatization process.

Diastereoselective synthesis of spiro[carbazole-3,5'-pyrimidines] and spiro[carbazole-3,1'-cyclohexanes] via four-component reaction.

Functionalized spiro[carbazole-3,5'-pyrimidines] and spiro[carbazole-3,1'-cyclohexanes] were efficiently synthesized in satisfactory yields with high diastereoselectivity by CuSO4 catalyzed multicomponent reaction of indole-2-acetate, aromatic aldehyde and 1,3-dimethylbarbituric acid or dimedone. The reaction was finished with sequential Diels-Alder reaction of both in situ generated indole-2,3-quinodimethane and a dienophile. Additionally, the initially formed spiro[carbazole-3,5'-pyrimidines] were converted to dehydrogenated spiro[carbazole-3,5'-pyrimidines] by DDQ oxidation. The initially formed spiro[carbazole-3,1'-cyclohexanes] were converted to δ-valerolactone-substituted carbazoles by a DDQ promoted Baeyer-Villiger oxidation process.

Multicomponent Reaction for Diastereoselective Synthesis of Spiro[carbazole-3,4'-pyrazoles] and Spiro[carbazole-3,4'-thiazoles].

In the presence of copper sulfate, the three-component reaction of aromatic aldehydes, ethylindole-3-acetate and 4-arylidene-5-methyl-2-phenylpyrazol-3-ones, in refluxing toluene afforded spiro[carbazole-3,4'-pyrazoles] in good yields with high diastereoselectivity. More importantly, the similar CuSO4 promoted the four-component reaction of two molecular aromatic aldehydes with ethylindole-3-acetate and 5-methyl-2-phenyl-pyrazol-3-one resulted in 2,4-diarylspiro[carbazole-3,4'-pyrazoles] in satisfactory yields. Additionally, CuSO4 promoted the four-component reaction of two molecular aromatic aldehydes, ethylindole-3-acetate and 2-phenylthiazol-4-one, in refluxing toluene gave 2,4-diarylspiro[carbazole-3,4'-thiazoles] with diastereomeric ratios in the range of 3:1 to 20:1.