Novel Synthesis of 2-(Trifluoromethyl)- and 2-(Perfluoroalkyl)-2-hydroxy-2<i>H</i>-chromenes and Their Regiospecific Reaction with Silyl Enol Ethers

Kharrat, Salem El; Laurent, Philippe; Blancou, H.

doi:10.1021/jo060765a

Cited by 32 publications

(16 citation statements)

References 45 publications

(28 reference statements)

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“…In previous articles [59,60,61,62,63,64,65] we have reported the synthesis of various perfluoroalkylated quinoline derivatives, by reacting perfluoroalkylated gem -iodoacyloxy derivatives 14 with substituted anilines 15 . Later we observed that the presence of a ketone in the medium leads to the formation of arylpyridiniums instead of quinolines; what suggested an interesting alternative to published synthetic methods, and led us to design a new and efficient synthesis of substituted 2-trifluoromethyl and 2-perfluoroalkyl- N -arylpyridinium derivatives 17 – 19 under mild reaction conditions and with very good yields.…”

Section: Introductionmentioning

confidence: 99%

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

et al. 2019

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We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N’-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated β-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson’s. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it.

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Section: Introductionmentioning

confidence: 99%

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

et al. 2019

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“…On the other hand, although introduction of fluorine atoms into organic compounds has been known as one of the best strategies for the enhancement or modification of their original biological activities [15,16,17,18,19], up to now there are limited reports on the preparation of 2-fluoroalkylated 2 H -chromenes. Laurent et al reported the synthesis of 2-(trifluoromethyl)- and 2-(perfluoroalkyl)-2-hydroxy-2 H -chromenes by intramolecular cyclization of 3-(perfluoroalkyl)-3-phenoxypropenals in the presence of aluminum chloride [20]. Wang et al .…”

Section: Introductionmentioning

confidence: 99%

An Efficient Solvent-Free Synthesis of 2-Hydroxy-2-(trifluoromethyl)-2H-chromenes Using Silica-Immobilized L-Proline

et al. 2013

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An efficient synthesis of 2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylates was carried out under solvent-free conditions in an oven or microwave oven via the Knoevenagel condensation of salicylaldehydes with ethyl trifluoroacetoacetate followed by intramolecular cyclization in the presence of silica-immobilized L-proline. The structures of the title compounds were characterized by IR, 1 H-NMR, 13 C-NMR, HRMS and X-ray single crystal diffraction. The improved method described herein is economical, easily-operated and environmentally friendly. Furthermore, the catalyst can be recovered conveniently and reused without obvious loss of activity.

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“…27-A affords another intermediate 2 27. B, which upon intramolecular heterocyclization forms the desired chromene 276. one of the emerging fields of modern catalysis research.…”

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confidence: 99%

Catalytic Synthesis of 2H-Chromenes

et al. 2015

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2H-Chromenes (2H-1-benzopyran derivatives) display a broad spectrum of biological activities. The 2H-chromene substructure is an important structural motif present in a variety of medicines, natural products, and materials showing unique photophysical properties. Hence, the structural importance of the benzopyran moiety has elicited a great deal of interest in the field of organic synthesis and chemical biology to develop new and improved synthesis of these molecular skeletons. This review gives an up-to-date overview of different catalytic methodologies developed for the synthesis of 2H-chromenes and is structured around the three main approaches applied in catalytic 2H-chromene synthesis: (I) catalysis with (transition) metals, (II) metal-free Brønsted and Lewis acid/base catalysis, which includes examples of nonenantioselective organocatalysis, and (III) enantioselective organo-catalysis. The section in which the metal-catalyzed reactions are discussed describes different ring-closing strategies based on (transition) metal catalysis, including a few enantioselective approaches. For most of these reactions, plausible mechanisms are delineated. Moreover, synthesis of some natural products and medicinally important drugs are included. Specific advantages and disadvantages of the several synthetic methodologies are discussed. The review focuses on catalytic 2H-chromene synthesis. However, for a complete overview, synthetic routes involving some stoichiometric steps and reactions producing ring-scaffolds that are closely related to 2H-chromenes are also included.

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Novel Synthesis of 2-(Trifluoromethyl)- and 2-(Perfluoroalkyl)-2-hydroxy-2H-chromenes and Their Regiospecific Reaction with Silyl Enol Ethers

Cited by 32 publications

References 45 publications

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

An Efficient Solvent-Free Synthesis of 2-Hydroxy-2-(trifluoromethyl)-2H-chromenes Using Silica-Immobilized L-Proline

Catalytic Synthesis of 2H-Chromenes

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