Diastereoselective Synthesis of Tetrahydrospiro[carbazole-1,3'-indolines] via an InBr3-Catalyzed Domino Diels-Alder Reaction.

A simple InBr3-catalyzed domino reaction of indoles, phenylacetylenes, and various 3-methyleneoxindolines in toluene is described. This reaction not only provided a convenient synthetic protocol for polysubstituted tetrahydrospiro[carbazole-1,3'-indolines] in good yields but also gave completely different diastereoisomers of the tetrahydrospiro[carbazole-1,3'-indolines] to that of the previously reported TfOH-catalyzed one-pot reaction of indoles, acetophenones, and 3-methyleneoxindolines. Additionally, the InBr3-catalyzed reaction of the initially prepared 1,1'-bis(indolyl)phenylethanes with 3-phenacylideneoxindolines also gave the corresponding tetrahydrospiro[carbazole-1,3'-indolines] in good yields and with excellent diastereoselectivity. The reaction mechanism involved the sequential in situ generation of reactive dienophilic 3-alkenylindole, the Diels-Alder reaction, and the Lewis acid controlled diastereoisomerization process.

Convergent Synthesis of Triindanone-Fused Spiro[bicyclo[2.2.2]octane-2,3'-indolines] via Domino Reaction of 1,3-Indanedione and 3-Methyleneoxindoles.

A triethylamine-promoted domino reaction of three molecular 1,3-indanediones with various 3-methyleneoxindoles in refluxing ethanol has been developed. Series of novel polycyclic triindanone-fused spiro[bicyclo[2.2.2]octane-2,3'-indoline] derivatives were successfully synthesized in satisfactory yields with high diastereoselectivity. This domino reaction was accomplished with in situ generation of active cyclic dienes by base-promoted cyclotrimerization or cyclotetramerization of 1,3-indanediones and sequential Diels-Alder reaction of active cyclic dienes with dienophilic 3-methyleneoxindoles.

Diastereoselective construction of carbazole-based spirooxindoles via the Levy three-component reaction.

The CuSO4 catalyzed three-component reaction of indole-2-acetate, aromatic aldehydes and 3-methyleneoxindoles in toluene at 130 °C afforded polysubstituted spiro[carbazole-3,3'-indolines] in good yields and with high diastereoselectivity. When isatylidene malononitriles were used as dienophiles, regio-isomeric spiro[carbazole-2,3'-indolines] were selectively obtained. A similar three-component reaction with 2-arylidene-1,3-indanediones resulted in polysubstituted spiro[carbazole-3,2'-indenes] in satisfactory yields and with high diastereoselectivity. The stereochemistry of the diastereoisomers of the spiro compounds was clearly elucidated by analysis of NMR spectra and determination of fourteen single crystal structures. The reaction mechanism included formation of reactive 2,3-dimethyleneindoline and a sequential Diels-Alder reaction.

Molecular diversity of the domino annulation reaction of 2-aryl-3-nitrochromenes with pivaloylacetonitriles.

In the presence of triethylamine, the domino annulation reaction of two molecules of pivaloylacetonitrile with one molecule of 2-aryl-3-nitrochromene in tetrahydrofuran resulted in the unprecedented imino-substituted dihydrofuro[2,3-c]chromene derivatives in high yields. More importantly, the above domino reaction in refluxing methanol or ethanol afforded alkoxy-substituted chromeno[3,4-b]pyridines in satisfactory yields. However, a similar reaction of benzoylacetonitrile with 2-aryl-3-nitrochromenes in basic medium gave the expected furo[2,3-c]chromene derivatives in moderate yields.