Two-step, regioselective, multigram-scale synthesis of 2-(trifluoromethyl)indoles from 2-nitrotoluenes

Walewska-Królikiewicz, Magdalena; Wilk, Bogdan K.; Kwast, Andrzej; Wróbel, Zbigniew

doi:10.1016/j.tetlet.2021.153515

Cited by 7 publications

(3 citation statements)

References 21 publications

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“…The authors of work [31] Another convenient approach to 3-trifluoromethyl-6-azaindoles was described in 2020 [32]. The hydration of trifluoracetyl derivative 48 in hydrochloric acid at 80 o C for 16 hours gave easy removing of the tri fluoroacetyl group to give 3-H 2-trifluoromethyl 6-azaindole.…”

Section: Annulation Of the Pyrrole Nuleus To The Pyridine Cyclementioning

confidence: 99%

Recent Advances in the Synthesis and Biological Activity of Pyrrolo[2,3-c]pyridines

Voloshchuk,

Ivonin

2024

J. Org. Pharm. Chem.

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Pyrrolo[2,3-c]pyridines (6-azaindoles) are the most promising nitrogen-containing heterocyclic compounds in the field of drug development. Exhibiting extraordinary versatility as pharmacophores, they are widely used in the development of kinase inhibitors, antiproliferative agents, and as potential therapeutic agents for the treatment of various diseases, including cancer and Alzheimer’s disease. A large number of works focusing on new methods and approaches in the synthesis of 6-azaindoes, as well as on the study of their biological activity, have been published worldwide. In our review, we tried to classify all currently known strategies for the construction of the 6-azaindole core, which were published within the last 15 years, the chemical diversity of the derivatives obtained, and their therapeutic potential in the context of medicinal chemistry. We hope that this work will generalize and facilitate the understanding of the strategy for the synthesis of pyrrolo[2,3-c]pyridines, as well as help scientists in their further research in the direction of 6-azaindoles.

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Section: Annulation Of the Pyrrole Nuleus To The Pyridine Cyclementioning

confidence: 99%

Recent Advances in the Synthesis and Biological Activity of Pyrrolo[2,3-c]pyridines

Voloshchuk,

Ivonin

2024

J. Org. Pharm. Chem.

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“…Both radical and electrophilic trifluoromethylations was performed using bis(perfluoroalkanoyl) peroxides [ 48 ], difluorodiiodomethane [ 49 ], hypervalent iodine reagents [ 50 , 51 , 52 , 53 ], CF 3 I [ 54 , 55 , 56 , 57 , 58 ], Umemoto’s reagents [ 59 , 60 ], [(phen)CuCF 3 ] [ 61 ], and CF 3 SO 2 Na [ 62 , 63 , 64 , 65 ]. Cyclization approaches are based on formation of C2-C3 bond as a key step and deal with transformations of compounds having ortho -toluidine fragment [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. One work reported transformation of 4- and 6-nitro-1-hydroxy indoles to NH indoles under treatment with bromoacetophenone ( Figure 2 ) [ 77 ].…”

Section: Introductionmentioning

confidence: 99%

An Efficient Approach to 2-CF3-Indoles Based on ortho-Nitrobenzaldehydes

et al. 2021

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The catalytic olefination reaction of 2-nitrobenzaldehydes with CF3CCl3 afforded stereoselectively trifluoromethylated ortho-nitrostyrenes in up to 88% yield. The reaction of these alkenes with pyrrolidine permits preparation of α-CF3-β-(2-nitroaryl) enamines. Subsequent one pot reduction of nitro-group by Fe-AcOH-H2O system initiated intramolecular cyclization to afford 2-CF3-indoles. Target products can be prepared in up to 85% yields. Broad synthetic scope of the reaction was shown as well as some followed up transformations of 2- CF3-indole.

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“…However, these reactions require the use of expensive trifluoro- and difluoromethylating reagents and often result in poor regioselectivity. In contrast, the current method we have developed is a highly efficient method that allows simultaneous (i) construction of a heterol ring and (ii) regioselective introduction of a trifluoro- or difluoromethyl group. , …”

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confidence: 99%

Two-Step Synthesis of 2-Trifluoromethylated and 2-Difluoromethylated Benzoheteroles Starting from HFO-1224yd(Z) and HFO-1233yd(Z)

2022

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An efficient two-step method for synthesizing 2-(trifluoromethyl)-and 2-(difluoromethyl)benzoheteroles bearing various substituents was developed. Commercially available HFO-1224yd(Z) or HFO-1233yd(Z) underwent the Suzuki−Miyaura coupling with arylboronic acids (acid esters) bearing a nucleophilic moiety at the ortho position to yield the corresponding β-fluoroβ-(trifluoromethyl)or β-fluoro-β-(difluoromethyl)styrenes, respectively. Treatment of the obtained styrenes with potassium phosphate induced nucleophilic 5-endo-trig cyclization to provide the corresponding 2-trifluoromethylated or 2-difluoromethylated indoles and benzofurans, as well as benzothiophenes.Letter pubs.acs.org/OrgLett

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Two-step, regioselective, multigram-scale synthesis of 2-(trifluoromethyl)indoles from 2-nitrotoluenes

Cited by 7 publications

References 21 publications

Recent Advances in the Synthesis and Biological Activity of Pyrrolo[2,3-c]pyridines

Recent Advances in the Synthesis and Biological Activity of Pyrrolo[2,3-c]pyridines

An Efficient Approach to 2-CF3-Indoles Based on ortho-Nitrobenzaldehydes

Two-Step Synthesis of 2-Trifluoromethylated and 2-Difluoromethylated Benzoheteroles Starting from HFO-1224yd(Z) and HFO-1233yd(Z)

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