Applications of Ethynylanilines as Substrates for Construction of Indoles and Indole‐Substituted Derivatives

Abstract

Indole is a core structure in many biologically important natural products such as heteroauxin, tryptophan, hypaphorine, bufotenine and gramine. Further, indole based natural products attracted the attention of many research groups due to their broad range of applications in pharmaceuticals, agrochemicals. Thus, it is essential to cover recent advances in the synthesis of indoles and its derivatives. Historically, indole and its derivatives are synthesized by numerous approaches, which is a vast subject and beyond the scope of this review. Herein, we particularly focused on the last five years progress in synthetic approaches for the construction of indole and its derivatives from the substituted 2‐ethynyl anilines using various approaches such as transition‐metal catalyzed cyclizations, metal‐free, and radical reactions. Therefore, we believe that summarizing these results may be very useful for chemists who are interested in the synthesis of heterocyclic compounds.

Synthesis of Indoles via Domino Reactions of 2-Methoxytoluene and Nitriles

“… , Consequently, numerous synthetic methods have been developed to access the 2-arylindole substructure. Classic routes include the Fischer indole synthesis while contemporary approaches employ transition-metal catalysts, including direct C-2 arylation of pre-existing indoles, − and intramolecular cyclization of functionalized anilines, − and many others. − Some of these approaches employ harsh reagents, highly functionalized precursors, or cryogenic temperatures that are challenging to access on scale. Therefore, more straightforward, efficient, and practical synthetic methods without addition of transition metals for the assembly of 2-arylindoles remain in demand.…”

Synthesis of Nitrogen-Containing Heterocyclic Scaffolds through Sequential Reactions of Aminoalkynes with Carbonyls

“…Versatile β-aminoalkyne building blocks for the synthesis of nitrogen-containing heterocyclic compounds are represented by 2-alkynylanilines 38 [ 55 , 56 , 57 ]. Their sequential reaction with carbonyl derivatives was directed towards the formation of different scaffolds by changing the reaction conditions.…”

Indole frameworks via transition-metal-free annulation: a current perspective

“…The recently published reviews mainly focussed on the transition-metalcatalyzed synthetic approaches towards the indole skeleton. [46][47][48][49][50][51][52][53][54][55][56] In 2018, Cheng and Shao published an interesting review on organocatalytic asymmetric transformations involving the cyclic imine moiety in indole analogues. 57 Immediately after, Neto and Zeni published a review article on metalfree synthesis of indoles from typical alkynes and a nitrogen source.…”