Latent Carbene: Diaminomethylation of Thiophenes

Koidan, G. N.; Hurieva, Anastasiya; Zahorulko, Serhii; Zadorozhny, A. M.; Lysenko, Viacheslav; Shvydenko, Tetiana; Русанов, Эдуард Б.; Kostyuk, Aleksandr

doi:10.1002/ejoc.202201048

Cited by 3 publications

(8 citation statements)

References 23 publications

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“…Recently we have demonstrated that the thiophenes bearing at least one electron-accepting substituent also react with silylformamidine 1 . Taking into account the fact that 1 is tolerant to many functional groups, this approach can be used for the preparation of various thiophene carbaldehydes . Here, we continue our study of the reaction on the example of variously substituted benzenes in order to figure out the factors that affect the reactivity of the substrates and to establish the reaction mechanism.…”

Section: Results and Discussionmentioning

confidence: 98%

“…Taking into account the fact that 1 is tolerant to many functional groups, this approach can be used for the preparation of various thiophene carbaldehydes. 11 Here, we continue our study of the reaction on the example of variously substituted benzenes in order to figure out the factors that affect the reactivity of the substrates and to establish the reaction mechanism. The introduction of acceptor groups into benzene moiety would make it more acidic and facilitate the reaction.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…9 Recently, we have reported the synthesis of silylformamidine 1 that has been claimed to exist in equilibrium with the corresponding carbene form 1′ and to react as a nucleophilic carbene (Figure 1). 10,11 It can be prepared in bulk quantities and stored for a long time. In this work, we investigated the reaction of silylformamidine 1 with substituted benzenes to find out the effect of substituents in the aromatic substrate, to estimate the scope of polyfunctional benzene derivatives that can be used in the reaction, and to investigate the reaction mechanism by means of quantum chemical calculations.…”

Section: ■ Introductionmentioning

confidence: 99%

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Latent Carbene in Diaminomethylation of Benzenes: Mechanism and Practical Application

Koidan,

Hurieva,

Rozhenko

et al. 2023

J. Org. Chem.

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Silylformamidine 1 exists in equilibrium with its carbenic form 1′ due to an easy migration of the silyl group. The reaction of 1 with variously substituted fluorobenzenes proceeds as an insertion of the nucleophilic carbene 1′ into the most acidic C−H bond upon mixing the reagents and does not require any catalyst. According to DFT calculations, the classical interpretation of the insertion reaction proceeding via a three-membered transition state structure requires high activation energy. Instead, low activation barriers are predicted for a transfer of the most acidic proton in the aromatic substrate to the carbene carbon. As the next step, a barrierless rearrangement of the formed ion pair toward the product completes the process. The reactivity of substituted benzenes in the reaction with silylformamidine can be roughly assessed by calculated pK a (DMSO) values for the C−H hydrogens. Benzene derivatives having pK a approx. less than 31 can undergo C−H insertion. The reaction provides aminals as the first products, which can easily be transformed into the corresponding aldehydes via acidic hydrolysis. As silylformamidine 1 is tolerant to many functional groups, the reaction can be applied to numerous benzene derivatives, making it a reliable strategy for application in organic synthesis.

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Section: Results and Discussionmentioning

confidence: 98%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Latent Carbene in Diaminomethylation of Benzenes: Mechanism and Practical Application

Koidan,

Hurieva,

Rozhenko

et al. 2023

J. Org. Chem.

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“…Finally, we have also developed a simple two-step procedure for formylation of halogen-substituted thiophenes. [14] Given the reactivity of fluoropyridines and their multiple CÀ H bonds, the development of efficient and regioselective functionalization methods is crucial.…”

Section: Introductionmentioning

confidence: 99%

“…Recently we have presented silylformamidine 1 as a new perspective reagent that owing to an easy migration of the silyl group exists in an equilibrium with its carbene form 1′ (Scheme 1). [12] It reacts with various compounds via an insertion into C−H bonds giving aminals as products [12,13] . The mechanism and scope of the reaction has also been studied for the reaction of 1 with 1,3‐dihalobenzenes [13] .…”

Section: Introductionmentioning

confidence: 99%

Straightforward Synthesis of Halopyridine Aldehydes via Diaminomethylation

Koidan

Zahorulko

Hurieva

et al. 2023

Chemistry A European J

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A novel two‐step method for formylation of fluoropyridines with silylformamidine 1 under catalyst‐free conditions was developed. A series of possible 18 fluoropyridines featuring one to four fluorine atoms were subjected to the reaction with 1 existing in equilibrium with its carbenic form 1′.12 Fluoropyridines were shown to react via C‐H insertion. The reaction proceeded either at β‐ or γ‐positions affording the corresponding aminals. The more fluorine atoms in pyridines, the easier the reaction proceeded. We also hypothesized that the pyridines in which the fluorine was substituted by other halogens would react in a similar manner. To test the hypothesis, a set of 3,5‐disubstituted pyridines with various combination of halogen atoms was prepared. 3,5‐Difluoropyridine was taken as a compound for comparison. All the pyridines in the series also reacted likewise. In most cases, hydrolysis of the aminals afforded the corresponding aldehydes. As DFT calculations indicate, the reaction mechanism includes deprotonation of pyridine by 1′ as a strong base and the following rearrangement of the formed tight ionic pair to the final product. An alternative reaction pathway involving addition of 1′ to the pyridine carbon with the following hydrogen transfer via a three‐membered transition state structure required much higher activation energy.

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Diaminomethylation of Pyrazoles

Koidan,

Zahorulko,

Hurieva

et al. 2024

Eur J Org Chem

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We studied the reaction of N‐alkyl(aryl)pyrazoles with silylformamidine 1 that exists in an equilibrium with its carbene form via migration of the trimethylsilyl group from the carbon to nitrogen atom. The carbene insertion proceeded at the C−H group in 5th position. N‐alkyl(aryl)pyrazoles featuring substituents such as Br, CN and NO2 group reacted readily affording the corresponding aminals. This approach allowed us to synthesize pyrazole dialdehyde and phosphine featuring a vicinal aldehyde group. The reaction does not require any catalyst. The insertion position was unambiguously confirmed by X‐ray analysis of an aminal and a set of derivatives. Aminals hydrolysis afforded the corresponding pyrazole carbaldehydes. Methanolysis of the aminals gave N‐methylimines of the pyrazolecarbaldehydes. Highly acidic nitro pyrazole instead of the insertion underwent silylation in 5th position.

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Latent Carbene: Diaminomethylation of Thiophenes

Cited by 3 publications

References 23 publications

Latent Carbene in Diaminomethylation of Benzenes: Mechanism and Practical Application

Latent Carbene in Diaminomethylation of Benzenes: Mechanism and Practical Application

Straightforward Synthesis of Halopyridine Aldehydes via Diaminomethylation

Diaminomethylation of Pyrazoles

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