Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• until NHC-copper complexes were first employed in CuAAC reactions. In 2006, the group of Nolan reported the application of air-stable complexes [(NHC)CuX] as efficient catalysts for CuAAC reactions with terminal and internal alkynes in aqueous solution or under neat conditions (Table 2) [146][147]. Also

• room temperature. However, in organic solvents such as THF, dichloromethane or tert-butanol, only poor conversions were observed with these [(NHC)CuX] catalysts. Nolan et al. also report on the possibility of using [(SIPr)CuCl] as a latent catalyst [148]. With DMSO as solvent, complex [(SIPr)CuCl] (2

• in the following order of ligands: neocuproine < 4,7-dimethoxy-1,10-phenanthroline < bathophenanthroline < 1,10-phenanthroline < 4,7-dichloro-1,10-phenanthroline [150]. In 2006, the group of Nolan introduced a new family of monocationic copper(I) NHC-complexes of general formula [(NHC)2Cu]X (X = BF4

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• ; cyclization; gold(I); gold catalysis; heterocycles; regioselectivity; Introduction In the last decade, phosphino and NHC–gold complexes have become prominent catalysts for the addition of nucleophiles to alkenes, alkynes and allenes [1][2][3][4][5][6][7][8][9][10][11]. Owing to the high affinity of gold(I

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• acceptable yield (59%) of the desired vinyl addition product 3a. Thermally-stable Ph3PAu(TA)OTf (TA-Au, 5%) slightly improved the performance, yielding 63% of the desired product and less hydration byproduct 4. When changing the primary ligand from triphenylphosphine to a NHC, the yield slightly decreased

Synthesis of axially chiral gold complexes and their applications in asymmetric catalyses

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 2224–2232, doi:10.3762/bjoc.9.261

• were also successfully synthesized and characterized by X-ray crystal diffraction. A weak gold-π interaction between the Au atom and the aromatic ring in these gold complexes was identified. Furthermore, we confirmed the formation of a pair of diastereomeric isomers in NHC gold complexes bearing an

• product in moderate yields and up to 29% ee. Keywords: asymmetric gold catalysis; chiral Au catalysts; gold-π interaction; NHC gold complex; Introduction After the long-held assumption of the non-reactivity of gold complexes, numerous reactions catalyzed by gold complexes have emerged in the last 2

• . However, chiral gold complexes [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45], especially chiral NHC–gold complex-catalyzed asymmetric reactions [46][47][48][49][50][51][52][53] are still uncommon. Very few efficient chiral NHC–gold catalysts have been known up to the year of 2013. So

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

• Adrián Gómez-Suárez,
• David J. Nelson,
• David G. Thompson,
• David B. Cordes,
• Duncan Graham,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2013, 9, 2216–2223, doi:10.3762/bjoc.9.260

• (NHC) ligands [8][9][10]. Recently, we have been very active in the synthesis and characterization of new gold(I)–NHC complexes and the study of their reactivity, with a special focus on the development of straightforward methodologies [11][12]. As a result of our investigations, we have recently

• reported the synthesis of [AuX(NHC)] (X = Cl, Br, I) complexes, directly from imidazolium and imidazolidinium salts and a suitable gold source, such as [AuCl(SMe2)], using K2CO3 as a base [13]. Moreover, we have also reported the synthesis of the first mononuclear gold(I) hydroxide species, [Au(OH)(IPr

• for the synthesis of such species using hydroxide 1: a) via transmetallation from either boronic acids or siloxides, or b) via deprotonation reactions of suitable substrates. We have applied the latter methodology to the synthesis of organogold–NHC complexes bearing several trans-ligands, such as

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

• good overall yields in a two step process. The key step involves the ring opening of the chiral epoxide with a nitrogen heterocyclic carbene (NHC) and further rearrangement to chiral N-(2,3-dihydroxypropyl)arylamides in high yields and enantioselectivity. During the reaction, no erosion in chiral

• purity was observed. Keywords: N-(2,3-dihydroxypropyl)arylamide; nitrogen heterocyclic carbenes (NHC); oxidative esterification of aromatic aldehyde; Introduction Chiral structures with three carbons are an integral part of many biologically active compounds including alkaloids, pharmaceuticals and

• (Scheme 2). The Mitsunobu reaction yielded the product (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (4a) [23][24][25][26][27] in 80% yield and in 99% ee. Then 4a was converted to hydroxypropyl benzoate 5a [28][29][30][31][32] by NHC-mediated oxidative esterification of aryl aldehydes (7a–f) [33][34][35

Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes

• Marcia E. Richard,
• Daniel V. Fraccica,
• Kevin J. Garcia,
• Erica J. Miller,
• Rosa M. Ciccarelli,
• Erin C. Holahan,
• Victoria L. Resh,
• Aakash Shah,
• Peter M. Findeis and
• Robert A. Stockland Jr.

Beilstein J. Org. Chem. 2013, 9, 2002–2008, doi:10.3762/bjoc.9.235

• , we extend the chemistry to the synthesis of arylgold compounds containing carbene ligands. Results and Discussion The synthesis of the carbene-ligated arylgold compounds was accomplished using (NHC)AuCl (NHC = IMes, SIMes, IPr, SIPr) precursors. For the initial screening runs, (IMes)AuCl and 4-tert

• chemistry was extended to other (NHC)AuCl compounds (Figure 1). It was anticipated that incorporating electron-donating groups into the aryl fragments on the gold would facilitate the cleavage of the organic group from the gold center through protodeauration; thus, –C6H4t-Bu and –C6H4OMe were selected as

• range of phenols with diphenylacetylene and 5-decyne serving as representative internal alkynes (Figure 2). Microwave and conventional heating were used in these reactions. Based upon the initial studies, the phosphine ligated catalyst 1, as well as NHC ligated catalysts 7–9 afforded high yields of the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• -aryltetrahydroisoquinoline 13 with an aliphatic aldehyde (Scheme 11) [78]. In the presence of a N-heterocyclic carbene (NHC), the aldehyde is converted to a chiral acyl anion or homoenolate equivalent 37, which is then added to the iminium ion 27 to form Csp3–Csp2 bonds asymmetrically. It is interesting to note that the use

• synthetic transformations to produce a diverse array of amines. Moreover, visible light photoredox catalysis has been merged with other types of catalysis, including enamine catalysis, N-heterocyclic carbene (NHC) catalysis, or copper acetylide formation. This dual catalysis approach has significantly

• reaction. Merging Au-based photoredox catalysis and Lewis base catalysis for the Mannich reaction. Merging Ru-based photoredox catalysis and Cu-catalyzed alkynylation reaction. Merging Ru-based photoredox catalysis and NHC catalysis. 1,3-Dipolar cycloaddition of photogenically formed azomethine ylides

Flow Giese reaction using cyanoborohydride as a radical mediator

• Takahide Fukuyama,
• Takuji Kawamoto,
• Mikako Kobayashi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2013, 9, 1791–1796, doi:10.3762/bjoc.9.208

• reductive radical addition reaction, better known as the Giese reaction, was historically carried out most by using tributyltin hydride as the radical mediator [8][9]. Recently borane derivatives such as borohydride reagents [10][11][12][13] or NHC-boranes [14][15][16][17][18] can be used in simple radical

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• demanding models [Pt(R)2(Im)] (R = SiMe3, Me; Im = imidazol-2-ylidene) appealed to the trans influence of both NHC and silyl ligands to explain the structure. However, a recent DFT investigation concluded that Y1 is better described as a Pt(0) σ-disilane complex [16] than as a Pt(II) disilyl species

• -heterocyclic carbene (NHC) ligands (Figure 6), which have been proven to be useful stabilizing electron-deficient transition-metal species [25][26][27]. In this regard, recent studies state that the use of IMes* (4,5-dimethyl-1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) and IMes (1,3-bis(2,4,6

• -trimethylphenyl)imidazol-2-ylidene) ligands in [Pt(Me)(NHC)2]+ T4 and [Pt(NHC’)(NHC)]+ T5 (NHC = IMes*, IMes; NHC’ = cyclometalated ligand) provides pure T-shaped species with no agostic stabilization [28]. Additionally, the resulting [Pt(Ar)(IMes*)2]+ T6 formed after C–H bond activation has also proven to be a

Synthesis and structure of trans-bis(1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene)palladium(II) dichloride and diacetate. Suzuki–Miyaura coupling of polybromoarenes with high catalytic turnover efficiencies

• Jeelani Basha Shaik,
• Venkatachalam Ramkumar,
• Babu Varghese and
• Sethuraman Sankararaman

Beilstein J. Org. Chem. 2013, 9, 698–704, doi:10.3762/bjoc.9.79

• stability and exceptional catalytic properties in comparison with their normal NHC counterparts. In particular triazolylidenes with sterically demanding mesityl and 2,4,6-triisopropylphenyl wingtip groups are catalytically very active. Polyphenylated arenes are a very important class of compounds and they

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

• Vladimir Lamm,
• Xiangcheng Pan,
• Tsuyoshi Taniguchi and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 675–680, doi:10.3762/bjoc.9.76

• -dimethylimidazol-2-ylidene borane. Aldehydes are reduced over 1–24 h at room temperature with 1 equiv of acetic acid and 0.5 equiv of the NHC-borane. Ketone reductions are slower but can be accelerated by using 5 equiv of acetic acid. Aldehydes can be selectively reduced in the presence of ketones. On a small

• scale, products are isolated by evaporation of the reaction mixture and direct chromatography. Keywords: NHC-borane; N-heterocyclic carbene borane; reduction; Introduction Reduction of carbonyl compounds is a common, fundamental chemical transformation. Among the numerous hydride reagents available

• decomposition with the release of hydrogen gas. Therefore, appropriate precautions are required for larger scale reactions as well as during transport and storage [5]. N-Heterocyclic carbene boranes (NHC-boranes) have emerged in recent years as a useful class of synthetic reagents, which have interesting

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• of carbinols to aldehydes or ketones using oxygen, visible light and mesoporous graphitic carbon nitride (mpg-C3N4) polymer as a metal-free photocatalyst [4]. As an extension of this method we were interested in a consecutive organocatalytic process using an N-heterocyclic carbene (NHC) together with

• mpg-C3N4 and oxygen. NHC-catalysts derived from the corresponding salts are known to react with aldehydes to provide I and lead after oxidation to acyl cation intermediate II. Subsequent reactions with nucleophiles give esters, amides or acids. Reagents such as MnO2 [5][6][7], DDQ, TEMPO and

• azobenzene [8][9][10][11][12][13][14][15][16][17][18] were described. The use of mpg-C3N4 should lead to a new process containing two subsequent organocatalytic reactions (Scheme 1). Results and Discussion In initial experiments we used 4-nitrobenzaldehyde as a model substrate. As NHC-salt we selected A

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

• Ismail Özdemir,
• Nevin Gürbüz,
• Nazan Kaloğlu,
• Öznur Doğan,
• Murat Kaloğlu,
• Christian Bruneau and
• Henri Doucet

Beilstein J. Org. Chem. 2013, 9, 303–312, doi:10.3762/bjoc.9.35

• Catalysis", Campus de Beaulieu, 35042 Rennes, France. Fax: +33 (0)2-23-23-69-39; Tel: +33 (0)2-23-23-63-84 10.3762/bjoc.9.35 Abstract New Pd–NHC complexes have been synthesized and employed for palladium-catalyzed direct arylation of pyrrole derivatives by using electron-deficient aryl chlorides as

• with heteroarenes. Keywords: aryl chlorides; atom-economy; C–H bond activation; C–H functionalization; carbenes; palladium; pyrroles; Introduction N-Heterocyclic carbenes (NHC) have emerged as an important class of ligands in the development of homogeneous catalysis [1][2][3][4][5][6][7][8][9]. Such

• ]. This is especially true for palladium-catalyzed coupling reactions. Pd–NHC catalysts [15] have proven to be excellent alternatives to catalytic systems involving palladium associated to tertiary phosphine ligands [16][17][18][19]. The introduction of aryl groups at C2 or C5 positions of pyrroles is an

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• ). Recently, iron and cobalt have been regarded as efficient catalysts for carbometalation of simple alkynes. Shirakawa and Hayashi reported that iron salts could catalyze arylmagnesiation of arylacetylenes in the presence of an N-heterocyclic carbene (NHC) ligand (Scheme 29) [103]. In 2012, Shirakawa and

• -catalyzed carbozincation of arylacetylenes and its application to the synthesis of tamoxifen. Bristol-Myers Squibb’s nickel-catalyzed phenylzincation. Iron/NHC-catalyzed arylmagnesiation of aryl(alkyl)acetylene. Iron/copper-cocatalyzed alkylmagnesiation of aryl(alkyl)acetylenes. Iron-catalyzed

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• PTCs of Denmark et al. The designed synthetic route to a hydroxy NHC from 4b. The reduction of amides 4 by LiAlH4 and BH3·THF. One-pot tandem cyclization of 6 in the presence of HC(OCH3)3. Supporting Information Supporting Information File 36: Full experimental details, analytical data and

Alkyne hydroarylation with Au N-heterocyclic carbene catalysts

• Cristina Tubaro,
• Marco Baron,
• Andrea Biffis and
• Marino Basato

Beilstein J. Org. Chem. 2013, 9, 246–253, doi:10.3762/bjoc.9.29

• Cristina Tubaro Marco Baron Andrea Biffis Marino Basato Dipartimento di Scienze Chimiche, Università degli Studi di Padova, via Marzolo 1, 35131 Padova, Italy 10.3762/bjoc.9.29 Abstract Mono- and dinuclear gold complexes with N-heterocyclic carbene (NHC) ligands have been employed as catalysts in

• (II) salts as catalyst [8][9][10]. Palladium complexes with N-heterocyclic carbene (NHC) ligands have since been showcased as highly efficient catalysts for this reaction [11][12][13][14]. Alternative catalytic systems based on salts or complexes of other noble metals, such as platinum [15][16][17

• few exceptions [36][40][44]. Finally, concerning the nature of the employed catalysts, simple gold salts or phosphino complexes of gold(I) were utilized in the majority of cases, although in recent years an increasing number of studies have been dealing with the application of NHC complexes of gold

N-Heterocyclic carbene–palladium(II)-1-methylimidazole complex catalyzed Mizoroki–Heck reaction of aryl chlorides with styrenes

• Ting-Ting Gao,
• Ai-Ping Jin and
• Li-Xiong Shao

Beilstein J. Org. Chem. 2012, 8, 1916–1919, doi:10.3762/bjoc.8.222

• Ting-Ting Gao Ai-Ping Jin Li-Xiong Shao College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Zhejiang Province 325035, People’s Republic of China 10.3762/bjoc.8.222 Abstract A well-defined N-heterocyclic carbene–palladium(II)-1-methylimidazole [NHC-Pd(II

• phosphine ligands, which can then increase the catalytic activity of the metal centre and the stability of the NHC–metal complexes, have attracted growing attention in the metal-catalyzed carbon–carbon and carbon–heteroatom bond-formation reactions during the past two decades [10][11][12][13][14][15

• ]. Consequently, since the seminal papers reported by Herrmann and co-workers [16][17], the NHC–Pd complexes have become a strong challenge to the phosphine–metal complexes in the Mizoroki–Heck reaction. Among the electrophiles participating in the NHC–Pd-complex-catalyzed Mizoroki–Heck reaction, organic iodides

Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts: Direct arylation of heterocycles

• Anthony R. Martin,
• Anthony Chartoire,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2012, 8, 1637–1643, doi:10.3762/bjoc.8.187

• Anthony R. Martin Anthony Chartoire Alexandra M. Z. Slawin Steven P. Nolan EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK 10.3762/bjoc.8.187 Abstract The use of [Pd(NHC)(cinnamyl)Cl] precatalysts in the direct arylation of heterocycles has been

• efficiency of well-defined palladium catalysts bearing NHC (N-heterocyclic carbene) ancillary ligands in classical cross-coupling reactions, they have rarely been applied to direct arylation procedures [9][10][11][12][13][14][15][16]. Among the family of [Pd(NHC)] complexes, the [Pd(NHC)(cin)Cl] (cin

• catalytic systems, and in the end to see whether the reactivity and application scope of these commercially available complexes could be broadened to include C–H bond functionalization transformations. We now report the activity of the [Pd(NHC)(cin)Cl] complexes 1–4 in the direct arylation of heterocycles

C2-Alkylation of N-pyrimidylindole with vinylsilane via cobalt-catalyzed C–H bond activation

• Zhenhua Ding and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2012, 8, 1536–1542, doi:10.3762/bjoc.8.174

• pyphos, which was the optimum ligand for the alkenylation reaction [33], was poorly effective (Table 1, entry 6). Additional screening of N-heterocyclic carbene (NHC) and phosphine ligands did not lead to an improvement of the catalytic efficiency (Table 1, entries 7–9). The reaction turned out to be

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

• including C–C bond construction, that is, formal addition of acyl anion equivalents generated from aldehydes 1 with NHCs, to α-imino esters 2 (Figure 1, (f)). Although a large number of NHC-catalyzed umpolung reactions, such as the benzoin reaction and Stetter reaction, have been developed [24][25][26][27

• , and atom-economical synthesis of the α-amino-β-keto esters by NHC-catalyzed cross-aza-benzoin reaction of aldehydes with α-imino esters under mild basic conditions. Results and Discussion First we initiated the cross-aza-benzoin reaction of benzaldehyde (1a) by employing 20 mol % of commercially

• reaction to give 5a in 42% yield (Table 1, entry 4). We reasoned that the acidity of the NHC precursor was important to promote the reaction under mild basic conditions (Table 1, entry 3 versus entry 4), and therefore we next investigated the substituent on the nitrogen atom of NHC. As envisaged, N

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

• ; kinetics; NHC activation; organocatalysis; structure reactivity relationships; Review Introduction The most comprehensive nucleophilicity and electrophilicity scales presently available, are based on Equation 1, in which electrophiles are characterized by one solvent-independent parameter E, and

• ]. Quantitative aspects of N-heterocyclic carbene (NHC) catalysis As the following discussion will focus on the difference between the kinetic term “nucleophilicity” and the thermodynamic term “Lewis basicity”, let us first illustrate this aspect by comparing the behavior of two well-known organocatalysts, 1,4

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• ][16][17]. MCA values obtained for NHC-carbenes are significantly larger than those obtained for nitrogen- and phosphorus-based nucleophiles and depend on both the structure of the heterocyclic ring system as well as the substituents attached to the respective 2- and 5-positions. With respect to the

• parameters N and slope parameters s of NHC-carbenes 334, 341 and 342 in THF [18][19][20]. The slowest reactions were found for triazolyl carbene 334 with N = 14.07 (s = 0.84). The imidazolyl carbene 341 (N = 21.75, s = 0.45) and the imidazolidinyl carbene 342 (N = 23.35, s = 0.40) are, in contrast, 108 to

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• stability of their metal complexes, and the convenient introduction of chiral elements, have also emerged as effective ligands for a number of homogeneous gold catalyzes [1][2][3][4][5][6][7][8]. However, during our ongoing survey of chiral NHC–Au(I) complexes in the literature, we only found a few unique

• papers of relevance. Tomioka and co-workers disclosed the first chiral NHC–Au(I) complex 1 (Figure 1), which was applied to catalyze the asymmetric cyclization of 1,6-enynes giving the corresponding cyclopentane derivatives with moderate enantioselectivity up to 59% [9][10]. Iglesias and co-workers

• reported a type of NHC–Au(I) complexes 2 containing C2-symmetric bis(NHC)-ligands with two imidazolin-2-ylidene moieties on a chiral dioxolane backbone, produced in up to 95% ee by hydrogenation of a prochiral alkene [11]. Recently, Toste and co-workers reported a novel family of axially chiral (acyclic

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• encouraged many chemists to search intensively for new NHC ligands, and this has led to the establishment of a very fruitful research area in organic chemistry [4][5][6][7][8][9][10]. A particularly interesting application comprises the use of “umpolung” reactions [11] (inversion of polarity) catalyzed by N

• -heterocyclic carbenes, such as the benzoin condensation and the Stetter reaction. In these reactions, the NHC effects an “umpolung” of the normal carbonyl reactivity, and the electrophilic aldehyde carbon atom thus becomes nucleophilic and can attack a variety of electrophiles. The story of “umpolung

• carbene precursors 7 has an important effect on the basicity and thus on the overall reactivity. In this way, the NHC and the conjugate acid can be present in sufficient quantities to promote a new form of cooperative catalysis. Further elaboration of this interesting observation led to the hypothesis