Radical [1,3] Rearrangements of Breslow Intermediates

Alwarsh, Sefat; Xu, Yi; Qian, Steven Y.; McIntosh, Matthias C.

doi:10.1002/anie.201508368

Cited by 17 publications

(15 citation statements)

References 44 publications

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“…They ascribe the results to reactions of radicals from homolysis of the Breslow intermediate observed in EPR spectra and computations. They propose that radicals lead to the products from 1 in Scheme , both the rearrangement and fragmentation forming via a radical pair from homolysis of the Breslow intermediate (Scheme ) . Recombination and disproportionation lead to both sets of products.…”

Section: Methodsmentioning

confidence: 99%

“…These potential side reactions and lack of controls permit neither confident assignment of a signal to the proposed radical pair nor a basis for quantitation. Attempts to detect or isolate TEMPO adducts that would be expected from radicals also gave negative results …”

Section: Methodsmentioning

confidence: 99%

“…Since we can detect the presence of fragmentation products at about 1 mol %, the rate constant for reaction of 4‐hydroxy‐TEMPO with 2 must be at least 10 6 s −1 . This suggests why McIntosh and co‐workers do not isolate TEMPO‐radical conjugates …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin‐Derived Breslow Intermediate

Bielecki

Kluger

2017

Angew Chem Int Ed

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Mandelylthiamin (1) is a conjugate of benzoylformate and thiamin that loses CO to form the classic Breslow intermediate (2), whose expected fate is formation of the thiamin conjugate of benzaldehyde (3). Surprisingly, it was observed that 2 decomposes to 4 and 5 and rearranges to 6 in competition with the expected protonation to give 3. Recent reports propose that the alternatives to protonation arise from homolysis followed by radical-centered processes. It is now found, instead, that the spectroscopic observations cited in support of the proposed radical pathways are likely to be the result of other events. An alternative explanation is that ionization of the enolic hydroxy group of 2 and resultant electronic reorganization leads to C-C bond cleavage and non-radical intermediates that readily form 4, 5, and 6.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin‐Derived Breslow Intermediate

Bielecki

Kluger

2017

Angew Chem Int Ed

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“…The realization that NHCs can stabilize radical centers [1][2][3][4][5] and therefore allow for a facile radical formation, is a fundamental one. Especially the observation that radicals of type I (Scheme 1) are formed even under non-oxidative conditions as in the benzoin reaction is hinting at the potential of new transformations by NHCs.…”

Section: Introductionmentioning

confidence: 99%

NHC‐Stabilized Radicals in the Formal Hydroacylation Reaction of Alkynes

et al. 2018

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Mechanistic details of transformations catalyzed by N‐heterocyclic carbenes (NHC) are currently of great interest, targeting questions on the active catalyst in operation and the structure and reactivity of key intermediates. These mechanistic studies are driven by the need to understand the big impact of subtle changes on the catalyst system on its reactivity, as well as to clarify the situation around the elusive intermediates in the classical catalytic cycle. In the activation process of aldehydes the formation of an enaminol structure, coined the Breslow intermediate, is widely accepted. Previously, however, we could prove that this enaminol has, besides its ionic reaction pathway, also the option to follow a radical pathway, by undergoing redox processes with the starting material. In the present study we aim to elucidate if these radical pathways are a more general phenomenon, specifically in the formal hydroacylation reaction of alkynes. The observation of radical species and computational analysis of key elemental steps in the radical and ionic pathways may lead to an onward development of chemistry based on NHC‐stabilized carbon radicals.

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“…Attempts to detect or isolate TEMPO adducts that would be expected from radicals also gave negative results. [7] It is well-established that 1 decarboxylates in neutral aqueous buffers to form 2,which rapidly undergoes fragmentation to 4 and 5 (and potentially other products). [5] Thus,we prepared 1 [12] and analyzed the products of its decarboxylation in phosphate buffers in D 2 Ob y 1 HNMR spectroscopy.…”

mentioning

confidence: 99%

The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin‐Derived Breslow Intermediate

Bielecki

Kluger

2017

Angewandte Chemie

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Mandelylthiamin (1)i saconjugate of benzoylformate and thiamin that loses CO 2 to form the classic Breslow intermediate (2), whose expected fate is formation of the thiamin conjugate of benzaldehyde (3). Surprisingly,i tw as observed that 2 decomposes to 4 and 5 and rearranges to 6 in competition with the expected protonation to give 3.R ecent reports propose that the alternatives to protonation arise from homolysis followed by radical-centered processes.I ti sn ow found, instead, that the spectroscopic observations cited in support of the proposed radical pathways are likely to be the result of other events.A na lternative explanation is that ionization of the enolic hydroxy group of 2 and resultant electronic reorganization leads to C À Cbond cleavage and nonradical intermediates that readily form 4, 5,and 6. Scheme 4. An anionic mechanism for the fragmentation and rearrangement reactions of the Breslow intermediate. Angewandte ChemieCommunications 6323

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Radical [1,3] Rearrangements of Breslow Intermediates

Cited by 17 publications

References 44 publications

The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin‐Derived Breslow Intermediate

The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin‐Derived Breslow Intermediate

NHC‐Stabilized Radicals in the Formal Hydroacylation Reaction of Alkynes

The Need for an Alternative to Radicals as the Cause of Fragmentation of a Thiamin‐Derived Breslow Intermediate

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