Progress in the Synthesis of 2,3-Disubstituted Indole by Cyclization

Abstract

In recent years, there are many reports about the synthesis of 2,3-disubstituted indole by cyclization. Most of these approaches are catalyzed by different transition metals and metal-free catalysis conditions using phenylnydrazines, anilines and nitrobenzenes as main substrates. These methods have been a powerful strategy to obtain 2,3-disubstituted indoles. The recent progress of the synthesis of 2,3-disubstituted indoles by cyclization with the different substrates systems is summarized.

Solvent-Mediated Tunable Regiodivergent C6- and N1-Alkylations of 2,3-Disubstituted Indoles with p-Quinone Methides

“…Most of these methods for functionalized 2,3-disubstituted/fused indoles include the architecture of the parent heterocycle by cyclization via different transition metals and metal-free catalysis conditions using phenylhydrazine, aniline, and nitrobenzene as main substrates. 8 Other approaches to these functionalized indoles involve derivatization of the indole nucleus via crosscoupling methodology or direct C−H/N−H activation. 9 Meanwhile, N1, C3, and C6 positions of 2,3-disubstituted indoles may exhibit mainly three types of nucleophilic behavior toward electrophiles due to their electronic nature (Scheme 1a).…”

“…Therefore, there is interest in the development of efficient methods to access 2,3-disubstituted indoles. Most of these methods for functionalized 2,3-disubstituted/fused indoles include the architecture of the parent heterocycle by cyclization via different transition metals and metal-free catalysis conditions using phenylhydrazine, aniline, and nitrobenzene as main substrates . Other approaches to these functionalized indoles involve derivatization of the indole nucleus via cross-coupling methodology or direct C–H/N–H activation …”

Recent Progress in the Transition Metal Catalyzed Synthesis of Indoles

“…Moreover, transition metal catalyzed cross-coupling reactions involving C-H activation are an alternative strategy to the traditional synthetic protocol and have recently increased importance for the construction of C-C and C-N bonds [4][5][6][7][8][9][10][11][12][13][14].…”

“…Then an intramolecular substitution occurs to form the pyrrole ring releasing the second nitrogen atom. R=Ar=Ph; X=H, 5-F, 5-Br, 5-CO 2 Me, 6-Me, 6-CO 2 Me, 7-Me, 7-MeO, 5,6-Me 2 (numbers refer to indole position) X=H; R=Ar=4-MeC 6 Also N-alkyl-N-arylhydrazines reacted with alkynes in the presence of a Co(III) catalytic system [27]. It is noteworthy that this reaction worked also with terminal alkynes, if a more cationic Co(III) species such as [Cp*Co(MeCN)3](SbF6)2 was employed.…”