FeCl₃·6H₂O as a Mild Catalyst for Nucleophilic Substitution of Symmetrical Bis(indoyl)methanes

Abstract

In this paper, unsymmetrical bis­(indolyl)­methane (BIM) and 3-alkylindole derivatives are smoothly synthesized from symmetrical BIMs with a variety of nucleophiles including heteroaromatic/aromatic compounds, allylsilane and alkynylsilane. FeCl3·6H2O is found to be a mild and highly effective catalyst for this nucleophilic substitution reaction in which N-methyl-2-phenylindole behaves as a good leaving group in the Csp3 –Csp2 bond cleavage reaction. The operational ease, nonexpensive and environmentally friendly catalyst, mild reaction conditions, broad functional group tolerance, and scalability of this reaction strategy are advantages of the present procedure.

Expedient Access to Indolyl-Substituted Tri- and Diarylmethanes and (±)-Colletotryptin E by Silica Sulfuric Acid Catalyzed Transindolylation

“…These compounds could be widely applied in diverse areas of chemistry. 4,16 Based on our experimental observations and the information in the relevant literature, 8,11 a plausible explanation for the formation of the double-transindolylation product might involve nucleophilic potentials and the increased steric enhancement of indole or other nucleophiles.…”

“…We recently developed a new procedure for the synthesis of nonsymmetrical 3,3′-and 2,3′-BIMs through a Fe-Cl 3 •6H 2 O-catalyzed substitution reaction of symmetrical 3,3′-BIMs with indole derivatives (Scheme 1E). 11 We successfully applied this strategy in a short total synthesis of (±)-gelliusine E and its derivatives. 12 Interestingly, some analogues of (±)-gelliusine E showed greater selectivity against the triple-negative breast cancer cells MDA-MB-231 compared with Vero cells.…”

Short Total Synthesis of (±)-Gelliusine E and 2,3′-Bis(indolyl)ethylamines via PTSA-Catalyzed Transindolylation

“…With the easily accessible coupling partners 8b and 13b in hand, the key transindolylation step was investigated (Scheme and Table ). A previously developed FeCl 3 ·6H 2 O-catalyzed transindolylation of 3,3′-BIMs enabled the unsymmetrical 3,3′-BIMs to be synthesized in good yields at room temperature . However, treatment of 8b with amino-protected serotonin 13b in the presence of FeCl 3 ·6H 2 O , (20 mol %) in a mixture of toluene/acetonitrile (ACN) (2:1) at room temperature afforded the desired 2,3′-BIEA 14bb in only very small amounts even after 24 h (Table , entry 1).…”

“…A previously developed FeCl 3 ·6H 2 O-catalyzed transindolylation of 3,3′-BIMs enabled the unsymmetrical 3,3′-BIMs to be synthesized in good yields at room temperature . However, treatment of 8b with amino-protected serotonin 13b in the presence of FeCl 3 ·6H 2 O , (20 mol %) in a mixture of toluene/acetonitrile (ACN) (2:1) at room temperature afforded the desired 2,3′-BIEA 14bb in only very small amounts even after 24 h (Table , entry 1). Increasing the catalyst loading (100 mol %) and reaction temperature (80 °C) for 24 h increased the yield of 14bb to 20% (entry 2).…”

“…However, most of the examples reported to date are limited to reactions of 2-indolyl­(aryl)­methanols substrates. Recently, our group has successfully developed a novel, efficient, and expedient approach for the construction of 3-alkylindole derivatives via the FeCl 3 ·6H 2 O-catalyzed nucleophilic substitution reaction of 3,3′-BIMs with a wide variety of nucleophiles under mild reaction conditions (Scheme C) . Inspired by these results, it was envisaged that (±)-gelliusine E ( 4 ) and 2,3′-BIEA analogues could be synthesized rapidly from 3,3′-BIEAs via transindolylation as the key step under environmentally friendly conditions.…”