Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• coupling of NHPI esters with aldehydes enabled by NHC catalysis [106]. The reaction proceeds with the catalyst NHC-1 at 60 °C and gives rise to ketones (Scheme 30A). The proposed mechanism begins with the reaction of benzaldehyde (143) and the NHC-catalyst 144 to form the neutral Breslow intermediate 145

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• used as organocatalyst in two classical umpolung reactions of cinnamaldehyde: its cyclodimerization and its oxidative esterification. Keywords: Breslow intermediate; cathodic reduction; flow electrochemistry; N-heterocyclic carbene; oxidative esterification; Introduction Ionic liquids (ILs) are well

• conversion to the corresponding thione (Scheme 2) [12]. NHCs are used as organocatalysts in many reactions of aldehydes (mainly aromatic) [13][14]. In fact, the reaction of NHCs with aldehydes can lead to the formation of the “Breslow intermediate” [15], in which the reactive character of the carbonyl carbon

• [33]. Flow electrochemistry was applied to oxidize the Breslow intermediate to the corresponding electrophilic acylthiazolium intermediate, which then functioned as an acyl-transfer reagent, reacting with alcohols or amines. To the best of our knowledge, only one research group reported the cathodic

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• 101 could be generated in an oxidative quenching cycle from THIQs 102 using a ruthenium-based photocatalyst and 1,3-dinitrobenzene (DNB) as a sacrificial oxidant (Scheme 13) [51]. These iminium ions could then be intercepted by a Breslow intermediate 103, formed between aldehydes 104 and the NHC

• . Another example was reported by Rovis in 2013 using enal 108 in the presence of chiral NHC 109 to form extended Breslow intermediate 110 (Scheme 14) [52]. Photoisomerisation of 110 is then required for the following spirocyclisation reaction to intermediate 111 to proceed, which then releases the NHC

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• precatalyst 3 [58], reversible addition of the free NHC I to the aldehyde leads to adduct II [59]. A subsequent deprotonation allows access to Breslow intermediate III, which can eliminate para-nitrobenzoate to leave azolium enol IV. Deprotonation gives azolium enolate intermediate V, which undergoes a formal

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• -diketones and 1,2,3-triketones with enones and ynones have been investigated. The diketones gave α,β-double acylation products via unique Breslow intermediates isolable as acid salts, whereas the triketones formed stable adducts with the NHC instead of the coupling products. Keywords: Breslow intermediate

• , the present reaction was proved to take place by an intramolecular process. A reaction mechanism is proposed in Scheme 2, which is similar to that with enones [15]. The monoacylated Breslow intermediate C is formed by addition of thiazolium NHC A to benzil (1a), followed by migration of the benzoyl

• NHC followed by migration of one neighboring acyl group to the central carbonyl oxygen would generate bisacylated Breslow intermediate 10 (Scheme 5). If this species behaves in a similar manner as the monoacylated intermediate C derived from 1,2-diketone 1, its reaction with enone 6a would be expected

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• popularly known as ‘Breslow intermediate’. This seminal discovery by Breslow paved the way for further developments in the area of carbene catalysis. Almost three decades later Bertrand and co-workers proved the existence of carbenes as catalytically active species in the benzoin reaction, with the

• anion equivalent 3 is known as the "Breslow intermediate". Its reaction with another molecule of aldehyde leads to the formation of an alkoxide intermediate 4. Proton transfer and subsequent release of thiazolylidene 1 affords the final product, the α-hydroxy ketone 5. Breslow demonstrated that

• with acetaldehyde. The reaction showed an interesting divergence in reactivity controlled by the catalysts, viz., the thiazolium salt 19 and triazolium salt 20. The thiazolium-derived carbene preferentially mediated the formation of the Breslow intermediate from the aromatic aldehyde followed by

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• by the Breslow intermediate 11 to provide the corresponding Aldol products [36]. Studer et al. reported the preparation of acids by an oxidation of Breslow intermediates with molecular oxygen [37][38][39]. The highly activated Breslow intermediate 11 formed by the addition of the NHC to the aldehydes

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

• Takuya Uno,
• Yusuke Kobayashi and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2012, 8, 1499–1504, doi:10.3762/bjoc.8.169

• . These findings indicate that the formation of benzoin is reversible via the Breslow intermediate, whereas the retro-benzoin reaction of cross-coupled product 5 does not occur under the present reaction conditions, and that the product 5 is formed under thermodynamic control. A plausible mechanism for

• the cross-aza-benzoin reaction is shown in Scheme 3. Carbene I is generated by deprotonation of triazolium salt 3e in the presence of K2CO3. The carbene I reacts with aldehyde 1 to afford Breslow intermediate II, which could lead to benzoin (6), or tetrahedral intermediate III when treated with α

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• ]) of the corresponding carbenes 49a–c (in kJ mol–1, MP2/6-31+G(2d,p)//B98/6-31G(d)), and the NICS(1) values of 47–49 (B3LYP/6-311+G(d)) (from [107]). Berkessel’s synthesis of a Breslow intermediate (51, keto tautomer) from carbene 43 [112]. Synthesis of O-methylated Breslow intermediates [114