Iron-Catalyzed <i>N</i>-Alkylation of Azoles via Oxidation of C−H Bond Adjacent to an Oxygen Atom

Pan, Shiguang; Liu, Jinhua; Li, Huanrong; Wang, Zhenyu; Guo, Xingwei; Li, Zhiping

doi:10.1021/ol100670m

Cited by 219 publications

(75 citation statements)

References 58 publications

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“…634 A variety of imidazoles but also a pyrazole and a triazole could be treated with cyclic and acyclic ethers to afford the 1-substituted azole derivatives in high yields.…”

Section: Scheme 332mentioning

confidence: 99%

Iron Catalysis in Organic Synthesis

2015

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“…634 A variety of imidazoles but also a pyrazole and a triazole could be treated with cyclic and acyclic ethers to afford the 1-substituted azole derivatives in high yields.…”

Section: Scheme 332mentioning

confidence: 99%

Iron Catalysis in Organic Synthesis

2015

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“…18 Although a mechanistic assessment of the FeCl 3 -catalyzed reactions of benzotriazole is not available, and neither are exactly comparable data in the other cases, KIE values have been reported for hemiaminal ether formation from imidazole and carbazole. 19,20 These data along with reaction conditions are shown in Table 3 and the results implicate a slow hydrogen atom abstraction step. 19,20 The KIE observed in the current competition experiment is comparable to these prior metal-catalyzed reactions.…”

Section: Resultsmentioning

confidence: 92%

“…19,20 These data along with reaction conditions are shown in Table 3 and the results implicate a slow hydrogen atom abstraction step. 19,20 The KIE observed in the current competition experiment is comparable to these prior metal-catalyzed reactions. Because formation of a reactive intermediate from THF is a likely occurrence before a product-forming step, we propose that C–H bond cleavage occurs in the slow step.…”

Section: Resultsmentioning

confidence: 92%

Ruthenium-Catalyzed C–H Bond Activation Approach to Azolyl Aminals and Hemiaminal Ethers, Mechanistic Evaluations, and Isomer Interconversion

et al. 2016

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C(sp3)–N bond-forming reactions between benzotriazole and 5,6-dimethylbenzotriazole with N-methylpyrrolidinone, tetrahydrofuran, tetrahydropyran, diethyl ether, 1,4-dioxane, and isochroman have been conducted using RuCl3•3H2O/t-BuOOH in 1,2-dichloroethane. In all cases, N1 and N2 alkylation products were obtained, and these are readily separated by chromatography. One of these products, 1-(isochroman-1-yl)-5,6-dimethyl-1H-benzotriazole, was examined by X-ray crystallography. It is the first such compound to be analyzed by this method, and notably, the benzotriazolyl moiety is quasi-axially disposed, consistent with the anomeric effect. This has plausible consequences, not observed previously. In contrast to other hemiaminal ether-forming reactions, which proceed via radicals, this Ru-catalyzed process is not suppressed in the presence of a radical inhibitor. Therefore, an oxoruthenium-species-mediated rapid formation of an oxocarbenium intermediate is believed to occur. In the radical-trapping experiment, previously unknown products containing both the benzotriazole and the TEMPO unit have been identified. In these products, it is likely that the benzotriazole is introduced via a Ru-catalyzed C–N bond formation, whereas C–O bond-formation with TEMPO occurs via a radical reaction. We show that reactions of THF with TEMPO are influenced by ambient light. A competitive reaction of THF and THF-d8 with benzotriazole indicated that C–H bond cleavage occurs ca. 5 times faster than C–D cleavage. This is comparable to other metal-mediated radical reactions of THF, but lower than that observed for a reaction catalyzed by n-Bu4N+I−. Detailed mechanistic experiments and comparisons are described. The catalytic system was also evaluated for reactions of benzimidazole, imidazole, 1,2,4-triazole, and 1,2,3-triazole with THF, and successful reactions were achieved in each case. In the course of our studies, we discovered an unexpected but significant isomerization of some of the benzotriazolyl hemiaminal ethers. This is plausibly attributable to the pseudoaxial orientation of the heterocycle in the products and the stability of oxocarbenium ions, both of which can contribute to C–N bond cleavage and reformation. Predominantly, the N2-isomers rearrange to the N1-isomers even upon storage at low temperature! This previously unknown phenomenon has also been studied and described.

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“…Although substrates with a strong electron-donating OMe group on the aryl ring give no product, weakly electron-donating and electron-withdrawing substituents on the aryl ring afforded the corresponding naphthalenes in moderate to high yields. A reaction pathway according to previous reports was proposed ( [42,[50][51][52]. Although the important intermediates in this reaction pathway are not observed, it is considered that a radical process is involved in this reaction because termination of the reaction occurs when 2.0 equiv.…”

Section: Scheme 19mentioning

confidence: 95%

Iron-Catalyzed Cross-Dehydrogenative-Coupling Reactions

Itazaki

Nakazawa

2015

Topics in Organometallic Chemistry

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Cross-dehydrogenative-coupling (CDC) reactions involving C-H bond activation are powerful tools for C-C bond formation and are highly significant from the perspective of atom economy. A variety of carbon-carbon bond-forming reactions utilizing various coupling partners are known today. Iron-catalyzed organic syntheses have attracted considerable attention because iron is an abundant, inexpensive, and environmentally benign metal. This chapter summarizes the development of iron-catalyzed CDC reactions, the reaction mechanism, and the role of the Fe species in the catalytic cycle in the period from 2007 to 2014.

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Iron-Catalyzed N-Alkylation of Azoles via Oxidation of C−H Bond Adjacent to an Oxygen Atom

Abstract: Azole derivatives were synthesized by iron-catalyzed oxidative reactions of azoles and ethers in good to excellent yields. A wide variety of azoles and ethers were selectively transformed into the corresponding oxidative coupling products under neutral reaction conditions.

Cited by 219 publications

References 58 publications

Iron Catalysis in Organic Synthesis

Iron Catalysis in Organic Synthesis

Ruthenium-Catalyzed C–H Bond Activation Approach to Azolyl Aminals and Hemiaminal Ethers, Mechanistic Evaluations, and Isomer Interconversion

Iron-Catalyzed Cross-Dehydrogenative-Coupling Reactions

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