NHC-catalysed benzoin condensation – is it all down to the Breslow intermediate?

Rehbein, Julia; Ruser, Stephanie-M.; Phan, Jenny

doi:10.1039/c5sc02186c

Cited by 96 publications

(83 citation statements)

References 35 publications

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“…As frequently reported, the chemistry of NHCs is strongly dependent on the lone pair hydrogen bond with donors ( Figure 8) [7,16,[78][79][80][81][82].…”

Section: Hydrogen Bond and Catalytic Activity Of Nhcmentioning

confidence: 93%

“…Hollóczki [7,16] emphasized that this result is related to the formation of a hydrogen bond between NHC and the ring hydrogen atom of NHCH + (present in IL but not in tetrahydrofuran, Figure 9). Accordingly, NHC should be deactivated in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide but not in tetrahydrofuran.…”

Section: Hydrogen Bond and Catalytic Activity Of Nhcmentioning

confidence: 99%

“…According to the hypothesis of Breslow, the heart of the mechanism is the nucleophilic attack of NHC to the carbonyl function of an aldehyde yielding a zwitterionic structure, which is converted (by an intramolecular proton transfer) into an acylanion equivalent (the Breslow intermediate). The coupling of the Breslow intermediate with a second aldehyde molecule yields the product (α-hydroxyketone, benzoin) and regenerates the NHC [15][16][17][18].…”

Section: Umpolung and The Peculiar Chemistry Of Nhcsmentioning

confidence: 99%

“… the effective presence of dimeric structures instead of (or in addition to) free NHC;  the influence of the dimeric partner on the NHC lone pair availability (i.e., on the catalytic efficiency) [16,19,[82][83][84];  the higher stability of the dimeric structure than that of free NHC; and  the nature of the "effective" catalyst, i.e., the attack to the active site of the substrate is carried out by free NHC (being the dimeric structure a precursor of free NHC) or by the dimer? In fact, a direct interaction between substrate and dimeric structure could not be rejected.…”

Section: Hydrogen Bond and Catalytic Activity Of Nhcmentioning

confidence: 99%

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Advances in the Knowledge of N-Heterocyclic Carbenes Properties. The Backing of the Electrochemical Investigation

2016

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In the last twenty years, N-heterocyclic carbenes (NHCs) have acquired considerable popularity as ligands for transition metals, organocatalysts and in metal-free polymer synthesis. NHCs are generally derived from azolium based salts NHCH+X− by deprotonation or reduction (chemical or electrochemical) of NHCH+. The extensive knowledge of the physicochemical properties of NHCH+/NHC system could help to select the conditions (scaffold of NHC, nature of the counter-ion X−, solvent, etc.) to enhance the catalytic power of NHC in a synthesis. The electrochemical behavior of NHCH+/NHC system, in the absence and in the presence of solvent, was extensively discussed. The cathodic reduction of NHCH+ to NHC and the anodic oxidation of NHC, and the related effect of the scaffold, solvent, and electrodic material were emphasized. The electrochemical investigations allow acquiring further knowledge as regards the stability of NHC, the acidic and nucleophilic properties of NHCH+/NHC system, the reactivity of NHC versus carbon dioxide and the effect of the hydrogen bond on the catalytic efficiency of NHC. The question of the spontaneous or induced formation of NHC from particular ionic liquids was reconsidered via voltammetric analysis. The results suggested by the classical and the electrochemical methodologies were compared and discussed.

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“…As frequently reported, the chemistry of NHCs is strongly dependent on the lone pair hydrogen bond with donors ( Figure 8) [7,16,[78][79][80][81][82].…”

Section: Hydrogen Bond and Catalytic Activity Of Nhcmentioning

confidence: 93%

Section: Hydrogen Bond and Catalytic Activity Of Nhcmentioning

confidence: 99%

Section: Umpolung and The Peculiar Chemistry Of Nhcsmentioning

confidence: 99%

Section: Hydrogen Bond and Catalytic Activity Of Nhcmentioning

confidence: 99%

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Advances in the Knowledge of N-Heterocyclic Carbenes Properties. The Backing of the Electrochemical Investigation

2016

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“…4 Only recently have such compounds been rigorously characterized, 5,6 and new chemistry continues to be revealed. 7 We recently reported that Breslow intermediates such as 2a derived from N-allyl benzothiazolium bromide and aromatic aldehydes could be captured in a unique Claisen rearrangement to provide 2-butenyl benzothiazoles (Scheme 2, R=H). 8,9 In the course of examining the scope of the reaction, we were surprised to find that N-cinnamyl substituted salt 3b provided principally [1,3]-rearrangement product 4b upon reaction with benzaldehyde, accompanied by only ca.…”

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confidence: 99%

Radical [1,3] Rearrangements of Breslow Intermediates

Alwarsh

Qian

et al. 2015

Angewandte Chemie

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Breslow intermediates that bear radical stabilizing N-substituents including benzyl, cinnamyl, and diarylmethyl undergo facile homolytic C-N bond scission under mild conditions to give products of formal [1,3]-rearrangement rather than benzoin condensation. EPR experiments and computational analysis support a radical mechanism. Implications for thiamine based enzymes are discussed. Keywords N-heterocyclic carbene; Breslow intermediate; radical; rearrangement; thiamineThiamine diphosphate (TDP) is an essential cofactor for all living things. It is involved in several critical metabolic processes, including the tricarboxylic acid cycle, the pentose phosphate pathway, and amino acid catabolism. 1,2 In 1958, Ronald Breslow postulated that key intermediates in thiamine catalyzed enzymatic pathways included an N-heterocyclic carbene (1) and an enaminol, e.g. 2 (Scheme 1). 3 In pyruvate decarboxylation, for example, addition of the TDP carbene to pyruvate is followed by extrusion of CO 2 to provide unstable enaminol 2. This and related heterocyclic enaminols have collectively been called "Breslow intermediates." 4 Only recently have such compounds been rigorously characterized, 5,6 and new chemistry continues to be revealed. 7 We recently reported that Breslow intermediates such as 2a derived from N-allyl benzothiazolium bromide and aromatic aldehydes could be captured in a unique Claisen rearrangement to provide 2-butenyl benzothiazoles (Scheme 2, R=H). 8,9 In the course of examining the scope of the reaction, we were surprised to find that N-cinnamyl substituted salt 3b provided principally [1,3]-rearrangement product 4b upon reaction with benzaldehyde, accompanied by only ca. 5% of the nominal [3,3]-product. The [1,3]-rearrangement product clearly implied a stepwise process in competition with the concerted rearrangement.Correspondence to: Matthias C. McIntosh, mcintosh@uark.edu. Supporting information for this article is given via a link at the end of the document. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptReaction of N-benzyl and N-diphenylmethyl benzothiazolium salts under the same conditions also yielded [1,3]-rearrangement products, albeit in diminished yield in the case of benzyl salt 3c (Scheme 3). The structures were confirmed by X-ray crystallography.Many NHC catalyzed reactions of aldehydes are presumed to proceed via a Breslow intermediate, 10 so these observations are relevant to NHC catalysis and catalyst design. Since benzothiazolium salts are only occasionally employed as NHC catalysts, 11 we exposed thiazolium and triazolium salts to the reaction conditions (Scheme 4). Reaction of thiazolium salt 3e with benzaldehyde gave high yield of [1,3]-rearrangement product 4e, as well as a few percent of ketone 5e. Treatment of symmetrically substituted 1,2,4-triazole 3f provided rearrangement product 4f in low yield as the only isolable product, although interestingly as a single regioisomer resulting from migration of the N-4 substituent. No significant ...

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