One-pot synthesis of tri- and di-fluoromethylated bis(indolyl)methanols via Friedel–Crafts-type acylation and alkylation

Abstract

A simple and efficient methodology for the first synthesis of tri- and di-fluoromethyl-bis(indolyl)-methanols has been demonstrated through the one-pot Friedel-Crafts-type acylation-alkylation of readily available indoles and fluorinated acids. This simple...

Divergent synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines

“…According to the experimental results and previous studies, [7][8][9][10][11][12] a plausible mechanism of this transformation was proposed (Scheme 6). In the presence of a catalytic amount of base, the difluoroacetaldehyde ethyl hemiacetal 2 has a tendency to remove ethoxide that can serve as a base catalyzing the next reaction cycle, resulting in the in situ generation of difluoroacetaldehyde.…”

“…5 The methods used for introducing a fluoromethyl group into a BIM scaffold generally involve step-by-step Friedel–Crafts-type alkylations, 8,9 probably because the electron-withdrawing fluoromethyl group can stabilize the fluorinated indole-3-methanol. The known method for the synthesis of difluoromethylated I3C, BIMs and indole-3-methanamines is the Friedel–Crafts reaction of indole with difluoromethylketones (Scheme 1a), 10 difluoroacetic acid (Scheme 1b) 11 or difluoroacetamide. 12 Recently, we reported a new method for the synthesis of difluoromethylated I3C from the reaction of indole with difluorovinyl arysulfonates (Scheme 1c).…”

Catalytic C(sp2)−H Trifluoroethylation of Indoles via Iron‐Carbene Insertion

“…Considering the possibility of industrial application, our catalyst of choice was porphyrinbased iron complex which is environmentally benign and readily available. After thorough investigation, herein, alternative to the Friedel-Crafts alkylation, [39][40][41][42][43] we report an efficient and mild methodology for fluoroalkylation of indole derivatives via an iron(III)-catalyzed CÀ H insertion reaction of fluoroalkyl carbene employing trifluoroacetaldehyde N-triftosylhydrazone as a carbene precursor and FeTPPCl as catalyst (Figure 1c).…”

Direct Fluoroacylation of Indole with Perfluoroalkyl Iodides

“…Therefore, we envisage that partially fluorinated compounds can be achieved by the following pathways, first the Na 2 S 2 O 4 -mediating perfluoroalkylation reaction of perfluoroalkyl iodides and then defluorinated hydrolysis in an autogenous acidic environment (Scheme c). Compared with traditional fluoroacylation reagents, ,− perfluoroalkyl iodides as a source for the introduction of a fluoroacylated unit have the following advantages: they are commercially available compounds, inexpensive, and easy to handle and store. We believe this transformation may provide a simple and alternative way for the fluoroacylation reaction.…”