Reassembly and functionalization of<i>N</i>-CF<sub>3</sub>pyridinium salts: synthesis of nicotinaldehydes

Liu, Xiaowei; Wang, Shuang; Gao, Chi; Guan, Wei; Wang, Mang

doi:10.1039/d2qo00242f

Cited by 3 publications

(7 citation statements)

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“…An approach to C(2)-thiolated nicotinaldehydes was recently developed through the use of N-CF 3 pyridinium salts 29. [28] Previously, the application of N-CF 3 pyridinium salts was limited due to difficulty of their synthesis. Wang and co-workers have developed a convenient method for the preparation of these compounds based on the direct N-trifluoromethylation of pyridines with PhICF 3 Cl under mild conditions.…”

Section: Transformation Of N-trifluoromethylpyridinium Saltsmentioning

confidence: 99%

“…[29] The resulting salts 29 successfully reacted with S-nucleophiles 9 a to form sulfur-containing nicotinaldehyde derivatives 30 (Scheme 10). [28] Reactions of various 4-amino-N-trifluoromethylpyridinium salts 29 with arylthiols 9 a bearing either electron-donating or electron-withdrawing groups resulted in products 30 in moderate to high yields (Scheme 10). A mechanism based on the ring-opening of the N-CF…”

Section: Transformation Of N-trifluoromethylpyridinium Saltsmentioning

confidence: 99%

“…Preparation of C(2)-functionalized nicotinaldehydes from N-CF 3 pyridinium salts. [28] Scheme 11. Proposed mechanism for transformation of N-CF 3 pyridinium salts.…”

Section: Nucleophilic Aromatic Substitution In N-(pyridyl)pyridinium ...mentioning

confidence: 99%

“…Proposed mechanism for transformation of N-CF 3 pyridinium salts. [28] pyridines 1 d to generate N-(pyridyl)pyridinium tetrafluoroborates 38 (Scheme 12). Further nucleophilic substitution (S N Ar) of the pyridine moiety in the pyridinium salts 38, isolated or generated in situ, with sulfur-containing nucleophiles such as thiols and sulfinates delivered arylthiopyridines 39 and sulfones 4, respectively.…”

Section: Nucleophilic Aromatic Substitution In N-(pyridyl)pyridinium ...mentioning

confidence: 99%

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Recent Progress in Functionalization of the Pyridine Ring through C−S Bond Formation under Transition Metal Catalyst Free Conditions

Tikhanova,

Bugaenko,

Karchava

2024

Adv Synth Catal

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Pyridines and quinolines substituted with sulfur‐containing functional groups are widely used as drugs, drug candidates, organic materials, N,S‐ligands and others. Traditional synthetic routes to produce these compounds are based on nucleophilic aromatic substitution reactions and transition metal‐catalyzed cross‐coupling reactions of (pseudo)halopyridines. While effective in many cases, both approaches are limited due to using forcing conditions and expensive, specifically designed catalytic systems. In the last decade, a number of innovative methods for the functionalization of the pyridine ring via the formation of a C–S bond have been developed. Most of these methods proceed through the direct or indirect C–H‐functionalization of unfunctionalized, thus avoiding the use of oftentimes not readily available halopyridines as the starting materials. Deoxygenative C–H‐functionalization of pyridine‐N‐oxides and deaminative transformation of aminopyridines have been also employed for the introduction of diverse organosulfur functionality into the pyridine ring. All these processes can be easily performed under mild conditions, typically affording value pyridines and quinolines in good to high yields. Usually being highly chemo‐ and regioselective, these methods allow the late‐stage functionalization of complex molecules including drugs and natural products. In this review, we summarize the most recent synthetic methods for functionalization of pyridines and fused pyridines with sulfur‐containing functional groups reported mostly since 2018. For a better understanding of the processes, the mechanisms of the described reactions are briefly discussed.

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Section: Transformation Of N-trifluoromethylpyridinium Saltsmentioning

confidence: 99%

Section: Transformation Of N-trifluoromethylpyridinium Saltsmentioning

confidence: 99%

“…Preparation of C(2)-functionalized nicotinaldehydes from N-CF 3 pyridinium salts. [28] Scheme 11. Proposed mechanism for transformation of N-CF 3 pyridinium salts.…”

Section: Nucleophilic Aromatic Substitution In N-(pyridyl)pyridinium ...mentioning

confidence: 99%

Section: Nucleophilic Aromatic Substitution In N-(pyridyl)pyridinium ...mentioning

confidence: 99%

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Recent Progress in Functionalization of the Pyridine Ring through C−S Bond Formation under Transition Metal Catalyst Free Conditions

Tikhanova,

Bugaenko,

Karchava

2024

Adv Synth Catal

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“…Subsequently, the authors’ group developed the reaction of the N -CF 3 nitrilium ions 51 with N-, O-, and S-nucleophiles, resulting in various N -CF 3 amidines, imidates, and Thioimidates [ 81 ]. Very recently, they utilized hypervalent iodine reagent for the trifluoromethylation of 4-alkylamino-pyridine to generate N -CF 3 pyridinium salt which could be further translated to 2-functionlized nicotinaldehydes [ 82 ].…”

Section: Five-membered Heterocyclesmentioning

confidence: 99%

A Brief Review on the Synthesis of the N-CF3 Motif in Heterocycles

et al. 2023

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The trifluoromethyl group is widely recognized for its significant role in the fields of medicinal chemistry and material science due to its unique electronic and steric properties that can alter various physiochemical properties of the parent molecule, such as lipophilicity, acidity, and hydrogen bonding capabilities. Compared to the well-established C-trifluoromethylation, N-trifluoromethylation has received lesser attention. Considering the extensive contribution of nitrogen to drug molecules, it is predicted that constructing N-trifluoromethyl (N-CF3) motifs will be of great significance in pharmaceutical and agrochemical industries. This review is mainly concerned with the synthesis of heterocycles containing this motif. In three-membered heterocycles containing the N-CF3 motif, the existing literature mostly demonstrated the synthetic strategy, as it does for four- and larger-membered heterocycles. Certain structures, such as oxaziridines, could serve as an oxidant or building blocks in organic synthesis. In five-membered heterocycles, it has been reported that N-CF3 azoles showed a higher lipophilicity and a latent increased metabolic stability and Caco-2-permeability compared with their N-CH3 counterparts, illustrating the potential of the N-CF3 motif. Various N-CF3 analogues of drugs or bioactive molecules, such as sildenafil analogue, have been obtained. In general, the N-CF3 motif is developing and has great potential in bioactive molecules or materials. Give the recent development in this motif, it is foreseeable that its synthesis methods and applications will become more and more extensive. In this paper, we present an overview of the synthesis of N-CF3 heterocycles, categorized on the basis of the number of rings (three-, four-, five-, six- and larger-membered heterocycles), and focus on the five-membered heterocycles containing the N-CF3 group.

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Tandem Ring-Contraction/Regioselective C–H Iodination Reaction of Pyridinium Salts

Tang

Zhao

et al. 2023

J. Org. Chem.

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A facile route for direct access to the 4-iodopyrrole-2-carbaldehydes from pyridinium salts has been successfully developed, which undergoes cascade pyrrole-2-carbaldehydes construction/selective C4 position iodination process. Using Na 2 S 2 O 8 as an oxidant and readily available sodium iodide as an iodine source, a variety of 4-iodopyrrole-2-carbaldehydes were obtained in good to excellent yields. Atom-and stepeconomy, good functional group tolerance, high regioselectivity, as well as mild conditions entail this transformation an alternative strategy for enriching pyrroles library.

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Reassembly and functionalization ofN-CF₃pyridinium salts: synthesis of nicotinaldehydes

Abstract: Reassembly and functionalization of N-CF3 pyridinium salts is reported. The cascade is initiated by hydrolytic ring-opening of N-CF3 pyridinium salts, followed by defluorination, intramolecular nucleophilic addition, intermolecular nucleophilic substitution, and...

Cited by 3 publications

References 38 publications

Recent Progress in Functionalization of the Pyridine Ring through C−S Bond Formation under Transition Metal Catalyst Free Conditions

Recent Progress in Functionalization of the Pyridine Ring through C−S Bond Formation under Transition Metal Catalyst Free Conditions

A Brief Review on the Synthesis of the N-CF3 Motif in Heterocycles

Tandem Ring-Contraction/Regioselective C–H Iodination Reaction of Pyridinium Salts

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Reassembly and functionalization ofN-CF3pyridinium salts: synthesis of nicotinaldehydes

Abstract: Reassembly and functionalization of N-CF3 pyridinium salts is reported. The cascade is initiated by hydrolytic ring-opening of N-CF3 pyridinium salts, followed by defluorination, intramolecular nucleophilic addition, intermolecular nucleophilic substitution, and...

Cited by 3 publications

References 38 publications

Recent Progress in Functionalization of the Pyridine Ring through C−S Bond Formation under Transition Metal Catalyst Free Conditions

Recent Progress in Functionalization of the Pyridine Ring through C−S Bond Formation under Transition Metal Catalyst Free Conditions

A Brief Review on the Synthesis of the N-CF3 Motif in Heterocycles

Tandem Ring-Contraction/Regioselective C–H Iodination Reaction of Pyridinium Salts

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Reassembly and functionalization ofN-CF₃pyridinium salts: synthesis of nicotinaldehydes