Reductively activated “polar” nucleophilic aromatic substitution of pentafluoronitrobenzene. The SRN2 hypothesis revisited

Marquet, Jacques; Jiang, Ziqi; Gallardo, Iluminada; Batlle, Anna; Cayon, E.

doi:10.1016/s0040-4039(00)73566-0

Cited by 21 publications

(11 citation statements)

References 36 publications

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“…A third interpretation of the result of Figure is shown in Scheme . It would take into account the elusive S RN 2 reaction ,− of which no example has ever be found. An attack of the nucleophile on ( E )-4-NO 2 − 1 •- would form an adduct (reaction 20), the cleavage (reaction 21) of which would lead to the radical anion 1-CH(CN) 2 −4-NO 2 − 2 •- and to the final product 2 −1-CH(CN) 2 −4-NO 2 − 2 along reaction 18.…”

Section: Resultsmentioning

confidence: 99%

Isomerization of Azo Compounds. Cleavage Recombination Mechanism of Azosulfides

et al. 1999

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(Z)-4-Nitrophenyl tert-butylsulfide [(Z)-4-NO2−1], upon formation of its radical anion, isomerizes to the (E)-isomer at a very fast rate of 6.3 × 106 s-1, about 103 times faster than azobenzene, while the 4-fluoro tert-butylsulfide (4-F−1) cleaves without isomerization. The particular behavior of 4-NO2−1 is related to the occurrence of a cleavage recombination mechanism, different from the usual inversion rotation mechanism. The existence of a reversible cleavage for the radical anion of 4-NO2−1 bears consequences on the mechanism of SRN1 reactions of azosulfides; the attack of the nucleophile would take place on the intermediate diazenyl radical and not on the ensuing aryl radical as previously proposed.

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Section: Resultsmentioning

confidence: 99%

Isomerization of Azo Compounds. Cleavage Recombination Mechanism of Azosulfides

et al. 1999

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“…This is attractive as oxidative addition of mercaptan derivatives is often challenging owing to the strength of many C(sp 3 )−S bonds. Hence, we considered an alternative strategy [48][49][50] beginning with the conversion of aliphatic mercaptans into redox-active thioethers [51][52] through our aforementioned SNAr protocol.…”

Section: Nickel-catalyzed Desulfurative Arylationmentioning

confidence: 99%

“…The concept of C−S bond activation has also been exploited for the functionalization of C−H /C−X bonds (X = halide). Organosulfur reagents like thianthrene sulfoxide, [60][61][62][63] dibenzothiophene S-oxide, [64][65] xanthate [66][67] , thiocarbamate, [68][69] and tetrafluoropyridinyl disulfide [48][49][50][51][52] can be added to arenes or organohalides to obtain sulfonium salts or sulfides, which contain a weak C−S bond that can be easily replaced in a reductive C−S bond cleavage step. Despite the success of the above methods, which are all based on C−S bond activation, one still lacks a generally applicable tool for the efficient conversion of mercapto groups into other functionalities.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Synthesis of Perfluoroaryl Sulfides and their Application in Desulfurative Nickel-Catalyzed Reductive Cross-Coupling

Lee

Hsu

Kao

et al. 2021

Preprint

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The C−S activation and sulfur removal from native thiols is challenging and limits the application of thiols as typical feedstock materials in organic synthesis despite their natural abundance. Herein, we describe a simple procedure to introduce a per-/polyfluoroaryl moiety, which serves as a redox-active scaffold, into alkyl/aryl thiols using nucleophilic aromatic substitution (SNAr) chemistry to activate the C−S bond. The per-/polyfluoroaryl group acts as an electron acceptor in single electron transfer events to generate radical intermediates through cleavage of the C−S bond of mercaptans and utilize them in nickel-catalyzed reductive cross-coupling reactions. In addition, using computational methods, we shed light on the mechanism of this class of SNAr reaction and show that the preference for a concerted or stepwise mechanistic pathway can be easily rationalized through a Marcus-type argument, as well as consideration of the relative stability of the potential energy surfaces.

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“…Additionally, we demonstrate how organic synthesis can exploit the perfluoroarylsulfides formed in the process described above by embarking upon the study of nickel catalyzed reductive Liebeskind−Srogl-type arylations, wherein the perfluoroaryl attached to the S atom acts as a redox-active scaffold to activate the C-S bond in the initial mercaptan. [48][49][50][51][52]…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Studies on the Synthesis of Perfluoroaryl Sulfides and their Application in Desulfurative Nickel-Catalyzed Reductive Cross-Coupling

Lee

Hsu

Kao

et al. 2021

Preprint

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Bougault in 1940, which uses a stoichiometric amount of Raney nickel as a single electron donor. [58][59] This hydrodesulfurization process is proposed to occur via fission of the C−S bond to give radical intermediates, followed by a hydrogen atom transfer to forge a new C−H bond. However, that process only allowed the removal of mercapto and other sulfur-containing groups. The concept of C−S bond activation has also been exploited for the functionalization of C−H /C−X bonds (X = halide). Organosulfur reagents like thianthrene sulfoxide, [60][61][62][63] dibenzothiophene S-oxide, [64][65] xanthate [66][67] , thiocarbamate, [68][69] and tetrafluoropyridinyl disulfide [48][49][50][51][52] can be added to arenes or organohalides to obtain sulfonium salts or sulfides, which contain a weak C−S bond that can be easily replaced in a reductive C−S bond cleavage step. Despite the success of the above methods, which are all based on C−S bond activation, one still lacks a generally applicable tool for the efficient conversion of mercapto groups into other functionalities. Recently, some elegant synthetic applications of alkyl radicals obtained through the desulfurization of mercaptans have been reported. Following their generation, the radicals can be added to unsaturated systems to access products of a formal alkylation process. [70][71][72] However, to the best of our knowledge, the application of alkyl radicals, generated in this manner, for arylation chemistry has not yet been reported. Nevertheless, we hypothesize that the alkyl radical could be intercepted by an aryl nickel (II) species to form a reactive Ni III intermediate, [73][74][75][76] that gives rise to a desulfurized arylation product after a facile reductive elimination (Scheme 2). In this study, we confirm our hypothesis and describe the first example of nickel-catalyzed reductive desulfurization leading to a direct C(sp 2 )−C(sp 3 ) cross-coupling. 77 Scheme 2. Nickel-catalyzed desulfurative cross-coupling of activated thioether with aryl halide RESULTS AND DISCUSSION Defluorosulfurization on Perfluoroarenes -OptimizationWe started our investigation by selecting pentafluoropyridine 1a as a representative perfluoroarene and thiol 2a as model substrates to examine the viability of our metal-free defluorosulfurization strategy (Table 1). After a thorough examination of the reaction conditions, we were delighted to find that employing triethylamine (0.3 mmol) in acetonitrile afforded 3a as a single regioisomer in 99% GC yield (Entry 1). The same reaction was performed on a gram-scale and 3a was isolated in 95% yield, demonstrating excellent amenity towards scale-up. In the screening of other bases, pyridine (15% yield, Entry 2) and 2,6-lutidine (52% yield, Entry 3) were found to be less effective, which we attributed to their lower basicity compared to triethylamine. We also tested Na2CO3 in DMSO 78 as an inorganic base; however, an inferior result was obtained (73% yield, Entry 4). On the other hand, changing acetonitrile to toluene only led to recovery of th...

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Reductively activated “polar” nucleophilic aromatic substitution of pentafluoronitrobenzene. The SRN2 hypothesis revisited

Cited by 21 publications

References 36 publications

Isomerization of Azo Compounds. Cleavage Recombination Mechanism of Azosulfides

Isomerization of Azo Compounds. Cleavage Recombination Mechanism of Azosulfides

Studies on the Synthesis of Perfluoroaryl Sulfides and their Application in Desulfurative Nickel-Catalyzed Reductive Cross-Coupling

Studies on the Synthesis of Perfluoroaryl Sulfides and their Application in Desulfurative Nickel-Catalyzed Reductive Cross-Coupling

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