A direct, concise, and atom-economical synthetic method for the generation of fused indoles, using a gold-catalyzed cascade cyclization of diynes, has been developed. The reaction gave various fused indoles, such as aryl-annulated[a]carbazoles, dihydrobenzo[g]indoles, and azepino- or oxepinoindole derivatives in good to excellent yields, through an intramolecular cascade 5-endo-dig hydroamination followed by a 6- or 7-endo-dig cycloisomerization, without producing theoretical byproduct. Three of the resulting indoles exhibited potent antifungal activities against T. mentagrophytes and T. rubrum, demonstrating the practical application of the described cascade reaction for drug discovery.

Abstract:Aniline-substituted diethynylarenes, which are readily synthesized through Sonogashira coupling reactions from commercially available 1,2-dihaloarenes, directly produce aryl-and heteroarylannulated[a]carbazoles by the gold-catalyzed intramolecular cascade hydroamination/cycloisomerization without producing theoretical by-products. This new atom-economical route is easily applicable to various aryl-annulated[a]carbazoles containing an alkyl, aryl or ester substituent.

The gold-catalyzed cascade intermolecular addition-intramolecular carbocyclization reaction of dialkynylbenzenes was developed. In this reaction, regioselective addition of an external nucleophile toward the terminal alkyne and subsequent 6-endo-dig cyclization proceeded to give the 1,3-disubstituted naphthalenes in good yields. The direct synthesis of disubstituted chrysenes via a gold-catalyzed addition and double cyclization cascade using a triyne-type substrate was also achieved.

A hydroamination-double hydroarylation cascade using aniline derivatives bearing a trienyne moiety as the substrate was efficiently promoted by a gold(I) catalyst to produce benzo[a]naphtho[2,1-c]carbazole derivatives in good yields. This reaction is applicable to various substituted trienyne-type anilines, including 2,3-diethynylthiophene derivatives. The reaction of anilines bearing a tetraenyne and pentaenyne moiety allows direct construction of highly fused carbazoles by tetra- and pentacyclization, respectively, through hydroamination and consecutive hydroarylation without producing any theoretical waste products from the substrates.