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.

Automated summary

The InBr3-catalyzed reaction efficiently synthesized polysubstituted tetrahydrospiro[carbazole-1,3'-indolines] with good yields and exhibited excellent diastereoselectivity in generating different diastereoisomers compared to the TfOH-catalyzed reaction. The reaction mechanism involved the in situ generation of reactive dienophilic 3-alkenylindole, the Diels-Alder reaction, and the Lewis acid controlled diastereoisomerization process.