Fischer indole synthesis applied to the total synthesis of natural products

Abstract

In this review, we are trying to underscore the application of FIS in one of the crucial step of indole construction in the total synthesis of biologically active natural products.

Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine

“…The Fischer indole synthesis [8,[20][21][22][41][42][43] is ac lassic tandem reaction that involves the condensation of an N-arylhydrazine 38 with an aldehyde/ketone 39 (Scheme 4A). This initial reaction gives an arylhydrazone intermediate (41), which tautomerizes to undergo a [ 3,3]-sigmatropic rearrangement before af inal cyclization-aromatization sequence to give an indole product (40).…”

SBA‐15‐Pr‐SO3H catalyzed one‐pot synthesis of indole derivatives via Fischer indole pathway

“…Also, indole alkaloid marine natural products have attracted lots of attention in the development of new drug leads for the control of cancer, parasitic, and neurological diseases. Among various methods for the preparation of indoles, Fischer indole method has been one of the most powerful approaches [7][8][9][10][11] and a wide spectrum of methodologies based on the efficient catalysts including Brønsted acids (H 2 SO 4 , HCl, PPA, AcOH, and TsOH), Lewis acids (ZnCl 2 , TiCl 4 ), solid acids (zeolite and montmorillonite clay), [12][13][14][15][16][17] heteropolyacids, [18] ionic liquids, [19,20] and ceric ammonium nitrate (CAN) [21] have been reported. Among various methods for the preparation of indoles, Fischer indole method has been one of the most powerful approaches [7][8][9][10][11] and a wide spectrum of methodologies based on the efficient catalysts including Brønsted acids (H 2 SO 4 , HCl, PPA, AcOH, and TsOH), Lewis acids (ZnCl 2 , TiCl 4 ), solid acids (zeolite and montmorillonite clay), [12][13][14][15][16][17] heteropolyacids, [18] ionic liquids, [19,20] and ceric ammonium nitrate (CAN) [21] have been reported.…”

“…[6] In this regard, numerous methods have been developed for the synthesis of indoles and more efficient and straightforward synthetic strategies are still in high demand due to their importance in material sciences and versatile therapeutic applications. Among various methods for the preparation of indoles, Fischer indole method has been one of the most powerful approaches [7][8][9][10][11] and a wide spectrum of methodologies based on the efficient catalysts including Brønsted acids (H 2 SO 4 , HCl, PPA, AcOH, and TsOH), Lewis acids (ZnCl 2 , TiCl 4 ), solid acids (zeolite and montmorillonite clay), [12][13][14][15][16][17] heteropolyacids, [18] ionic liquids, [19,20] and ceric ammonium nitrate (CAN) [21] have been reported.…”

Iodospirocyclization of Tryptamine‐Derived Isocyanides: Formal Total Synthesis of Aspidofractinine

“…[1] These compounds have attracted tremendous interest from the synthetic community as ar esult of their diverse biological activities as well as their challenging molecular architectures. [2] In particular spiroindoline alkaloids ( Figure 1) have garnered much attention, as demonstrated by the high number of approaches to construct the spirocyclic unit. [3] Besides the interrupted Fischer indole synthesis and aniline condensation cyclizations, the most common strategy is the intramolecular dearomatization of indoles to form spiroindolenines.Noteworthy within this field is the work by MacMillan et al,w ho have developed an organocatalytic dearomative cascade approach toward arange of indoline alkaloids.…”