Catalytic, Atom‐Economical Radical Arylation of Epoxides

Gansäuer, Andreas; Behlendorf, Maike; Laufenberg, Daniel von; Fleckhaus, André; Kube, Christian; Sadasivam, Dhandapani V.; Flowers, Robert A.

doi:10.1002/anie.201200431

Cited by 130 publications

(83 citation statements)

References 40 publications

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“…The reaction of 3 is too slow to be useful in typical radical chain reactions. However, reactions under our catalytic reaction conditions [6] with radicals similar to 3 were successful, too (see Scheme 4). Nevertheless, the transformations are, in agreement with the calculations, clearly more demanding than those with radicals similar to 1 and thus, more elaborate catalysts and the use of additives to enhance catalyst stability is essential.…”

Section: Resultsmentioning

confidence: 91%

“…Radical-based transformations are amongst the most attractive methods for the use in catalytic cycles due to the ease of radical generation, high functional group tolerance, and selectivity in C–C bond formation [3–5]. Recently, we have reported a novel catalytic reaction, a radical arylation of epoxides [6–8] proceeding via catalysis in single electron steps (for experimental results see Scheme 1) [9–10]. The C–C bond forming step of the catalytic cycle is an intramolecular alkyl radical addition to substituted anilines.…”

Section: Introductionmentioning

confidence: 99%

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Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

Gansäuer¹,

Seddiqzai²,

Dahmen³

et al. 2013

Beilstein J. Org. Chem.

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SummaryThe intramolecular radical addition to aniline derivatives was investigated by DFT calculations. The computational methods were benchmarked by comparing the calculated values of the rate constant for the 5-exo cyclization of the hexenyl radical with the experimental values. The dispersion-corrected PW6B95-D3 functional provided very good results with deviations for the free activation barrier compared to the experimental values of only about 0.5 kcal mol−1 and was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of the molecules is important and that a combination of electrophilic radicals with preferably nucleophilic arenes results in the highest rate constants. This is opposite to the Minisci reaction where the radical acts as nucleophile and the arene as electrophile. The substitution at the N-atom of the aniline is crucial. Methyl substitution leads to slower addition than phenyl substitution. Carbamates as substituents are suitable only when the radical center is not too electrophilic. No correlations between free reaction barriers and energies (ΔG ‡ and ΔG R) are found. Addition reactions leading to indanes or dihydrobenzofurans are too slow to be useful synthetically.

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Section: Resultsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

Gansäuer¹,

Seddiqzai²,

Dahmen³

et al. 2013

Beilstein J. Org. Chem.

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“…[14] By combining kinetic, EPR, and synthetic experi-ments with theoretical methods,w eh ave shown that the catalytic cycle is rather unusual in having ar esting state that leads to an inverse reaction order with respect to the epoxide ( Figure 6). …”

Section: Angewandte Chemiementioning

confidence: 99%

Highly Active Titanocene Catalysts for Epoxide Hydrosilylation: Synthesis, Theory, Kinetics, EPR Spectroscopy

et al. 2016

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A catalytic system for titanocene-catalyzed epoxide hydrosilylation is described. It features a straightforward preparation of titanocene hydrides that leads to a reaction with low catalyst loading, high yields, and high selectivity of radical reduction. The mechanism was studied by a suite of methods, including kinetic studies, EPR spectroscopy, and computational methods. An unusual resting state leads to the observation of an inverse rate order with respect to the epoxide.

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“…9 Doyle reported a nickel-catalyzed coupling with arylboronic acids that formed rearranged products 4 , 10 similar to related reactions with allylmetal reagents. 11 While Flowers and Gansäuer recently extended Ti(III)-epoxide chemistry 12 to the intra-molecular, internal arylation of epoxides, 13 the intermolecular arylation of epoxides to form products 2 and 3 remains limited to traditional methods.…”

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confidence: 99%

Nickel-Catalyzed Regiodivergent Opening of Epoxides with Aryl Halides: Co-Catalysis Controls Regioselectivity

2013

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Epoxides are versatile intermediates in organic synthesis, but have rarely been employed in cross-coupling reactions. We report that bipyridine-ligated nickel can mediate the addition of functionalized aryl halides, a vinyl halide, and a vinyl triflate to epoxides under reducing conditions. For terminal epoxides, the regioselectivity of the reaction depends upon the co-catalyst employed. Iodide co-catalysis results in opening at the less hindered position via an iodohydrin intermediate. Titanocene co-catalysis results in opening at the more hindered position, presumably via TiIII-mediated radical generation. 1,2-Disubstituted epoxides are opened under both conditions to form predominantly the trans product.

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Catalytic, Atom‐Economical Radical Arylation of Epoxides

Abstract: Scheme 1. Proposed catalytic cycle. Cp = cyclopentadienyl, M = metal.

Cited by 130 publications

References 40 publications

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

Highly Active Titanocene Catalysts for Epoxide Hydrosilylation: Synthesis, Theory, Kinetics, EPR Spectroscopy

Nickel-Catalyzed Regiodivergent Opening of Epoxides with Aryl Halides: Co-Catalysis Controls Regioselectivity

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