Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• after HWE olefination using dimethyl phosphonoacylsilane 54, was found to facilitate the NHC-catalyzed reduction and gave in this way the dipeptide isostere 56 in excellent yield. The defluorinative reduction could also be performed using samarium iodide. Altman and co-workers proposed the synthesis of

• -ψ[(Z)-CF=CH]-Phe by Dory and co-workers. Diastereoselective addition of Grignard reagents to sulfinylamines derived from α-fluoroenals by Pannecoucke and co-workers. NHC-mediated synthesis of monofluoroalkenes by Otaka and co-workers. Stereoselective synthesis of Boc-Tyr-ψ[(Z)-CF=CH]-Gly by Altman

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides

• Peter T. Kaplan,
• Jessica A. Lloyd,
• Mason T. Chin and
• David A. Vicic

Beilstein J. Org. Chem. 2017, 13, 2297–2303, doi:10.3762/bjoc.13.225

• facilitate meaningful comparative studies, such as structural and electrochemical ones [2]. N-Heterocyclic carbene (NHC) complexes of copper such as A1 (Scheme 1) were the first well-defined and structurally characterized copper–CF3 complexes that display activity for the trifluoromethylation of aryl halides

• complexes of copper B1 were reported shortly after the NHC counterparts [5][12] and have reached much success in chemical synthesis due to the ease of preparation and the low cost of the phenanthroline ancillary ligand. [(phen)CuCF3] can now be purchased commercially, or prepared in situ by a variety of

• as the major fluorine-containing product. Because our group has developed the NHC-based copper reagents for trifluoromethylation reactions [10][11], we were interested in comparing the effects of electronics and sterics of the aryl halides using the NHC-based systems A1 and A2 with the phen system B2

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• ]. b) Multistep and multicomponent synthesis of Re-complexes [176]. c) Mechano-synthesis of NHC-Au complex [177]. Mechanochemical activation of C–H bond of unsymmetrical azobenzene [178]. Mechanochemical synthesis of organometallic pincer complex [179]. Mechanochemical synthesis of tris(allyl)aluminum

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

• ring-enlargement procedure to afford cyclic 1,4-diketones IV. With respect to the active species in the Stetter reaction, aminoenols II (G = H, Breslow intermediates) had been postulated as true nucleophiles for a long time and those generated from imidazolinium NHC were recently isolated in pure form

• [17][18]. In the reaction of benzils with thiazolium NHC, aminoenol esters II (G = C(O)R1) could be formed similarly, but this active species were found to exist as isolable acid salts unexpectedly. Moreover, the reactivity of 1,2,3-triketones was also investigated in comparison with that of 1,2

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• a bulky monodentated phosphine (Scheme 1, reaction 1) [32]. More recently, important efforts have been made in order to develop new methodologies towards more effective and selective catalytic systems, such as the introduction of highly active N-heterocyclic carbene (NHC) catalysts reported by

• (acac)2. However, and despite the good selectivity obtained towards the tail-to-tail dimer 2-TT, this Pd/NHC catalysis required to be applied under pressure conditions (30 or 50 bar) for attaining the reported performance. Therefore, it would be highly desirable to develop simple, more readily available

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• properties [14]. The Ni-catalyzed C–S cross-coupling reactions generally involved Ni salts [15][16][17][18], Ni–phosphine complexes [19][20][21], or Ni–NHC complexes [22][23], although the actual catalyst is believed to be a Ni(0)/Ni(I) species [16][17][18][19][20][21]. NiO supported on zirconia (NiO–ZrO2

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• materials via a simple method. Their corresponding water soluble Pd–NHC catalysts, in situ generated from the imidazolium salts L1–L3 and Na2PdCl4 in water, showed impressive catalytic activity for aqueous Mizoroki–Heck reactions. The kinetic study revealed that the Pd catalyst derived from the imidazolium

• (NHCs) have been recognized as the preferable candidates [35][36]. In contrast to common phosphine- and nitrogen-based ligands, NHCs exhibit stronger σ-donating and weaker π-accepting properties, which make the corresponding Pd–NHC complexes more air and water stable. Furthermore, the convenient

• functionalization of the N atom of the NHC ring allows for the possible incorporation of water soluble moieties, thus providing more opportunities for water soluble catalyst design [37][38][39]. Since the pioneering report of a sulfonate-functionalized NHC ligand by Shaughnessy [40], a number of water-soluble NHC

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• effective strategies to construct biologically active spirocyclic oxindoles [65][66][67][68], we have built successfully interesting spirooxindoles via an NHC-catalyzed [4 + 2] annulation involving an oxidative γ-carbon activation of common α,β-unsaturated aldehydes [68]. Herein, we report another effective

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• developed an acyl anion addition promoted by N-heterocyclic carbenes (NHC) that furnished bicyclic furanones via Stetter addition [21]; later, the You group developed an extension of this theme using the same catalytic manifold [22]. More recently, the Corey group has enabled the enantioselective conjugate

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• to cis-trihydroxyindano[2,1-a]indan-5-ones 74 (Scheme 25). Another example of the 1-indanone synthesis using N-heterocyclic carbenes (NHC) has been described by Gravel et al. [50][51]. The benefit of the described reaction was a rapid construction of three new carbon–carbon bonds and a carbon

• -1,3-indanodiones 77 (Scheme 26). It has been found that the intermediate 79 underwent the Stetter reaction to form the enolate intermediate 80, which next was transformed to the intermediate 81 via aldol condensation. The release of NHC gave the β-hydroxy ketone 82, which was deprotonated to enolate

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• monodecyanated products 69a,b. Bicyclic lactones 70a,b are then obtained in 3 steps in 41% and 51% yields, respectively, from 69a,b. Later Curran’s group discovered that NHC-boryl radicals, generated from NHC-boranes (N-heterocyclic carbene boranes), abstracted the cyano group from various organic nitriles and

• dinitriles and applied this reaction for the synthesis of new NHC-boryl nitrile and dinitrile compounds [121]. They observed that malononitrile was the most efficient donor to produce boryl nitriles and concluded that substituted malononitriles would be decyanated by NHC-boranes. For this transformation

• , malononitriles are reacting with a slight excess of NHC-borane 71, in refluxing t-BuOH with DTBP (di-tert-butylperoxide) as radical initiator. The yields are attractive while roughly comparable amounts of boryl nitriles 74 and 75 are formed (Scheme 23). Malononitriles 72d,e are successfully reduced to 73d,e

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• disappeared after the Passerini reaction, while all other DHMP signals, i.e., the NHC at 9.2 ppm, the CHNH at 5.2 ppm or the CCH3 at 2.3 ppm, did not shift. Furthermore, the new characteristic signals for the CCHO at 4.9 ppm, the C(CH3)3 at 1.2 ppm and the terminal CH2CH3 methyl group at 0.84 ppm strongly

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• ). Keywords: C–C coupling; continuos-flow; diketone; electron-transfer; umpolung; Introduction The polarity reversal (umpolung) of carbonyl compounds by N-heterocyclic carbene (NHC) or cyanide catalysis represents a straightforward strategy for the synthesis of valuable molecules such as, among the many

• examples, α-hydroxy ketones (benzoin reaction) and 1,4-diketones (Stetter reaction) [1][2][3][4]. The synthetic utility of the umpolung methodology has therefore spurred intensive research on process intensification through the heterogeneization of NHC catalysts [5][6][7][8][9] for facilitating the post

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• .12.264 Abstract The mesomeric betaine imidazolium-1-ylphenolate forms a borane adduct with tris(pentafluorophenyl)borane by coordination with the phenolate oxygen, whereas its NHC tautomer 1-(2-phenol)imidazol-2-ylidene reacts with (triphenylphosphine)gold(I) chloride to give the cationic NHC complex [Au

• (NHC)2][Cl] by coordination with the carbene carbon atom. The anionic N-heterocyclic carbene 1-(2-phenolate)imidazol-2-ylidene gives the complexes [K][Au(NHC−)2], [Rh(NHC−)3] and [Ni(NHC−)2], respectively. Results of four single crystal analyses are presented. Keywords: anionic ligand; carbene

• tautomer; imidazol-2-ylidene; mesoionic compound; mesomeric betaine; Introduction Since the first isolation of a stable N-heterocyclic carbene (NHC) [1] in 1991 this compound class has provided numerous highly efficient ligands of NHC-metal catalysts for cross-coupling reactions [2][3][4][5][6][7

Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• data and XYZ coordinates for all compounds. Acknowledgements This work was supported in part by the Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET), Secretaría de Ciencia y Tecnología (SECYT-UNC) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT). NHC gratefully

Correction: 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, 2124–2124, doi:10.3762/bjoc.12.201

Experimental and theoretical investigations on the high-electron donor character of pyrido-annelated N-heterocyclic carbenes

• Michael Nonnenmacher,
• Dominik M. Buck and
• Doris Kunz

Beilstein J. Org. Chem. 2016, 12, 1884–1896, doi:10.3762/bjoc.12.178

• (current address of corresponding author) 10.3762/bjoc.12.178 Abstract Rh(CO)2Cl(NHC) complexes of dipyrido-annelated N-heterocyclic carbenes were prepared. From the C–H coupling constant of the respective imidazolium salts and the N–C–N angle of the N-heterocyclic carbene (NHC), a weaker σ-donor

• highest for the pyrido-annelated carbene. Going from the free carbene to the Rh(CO)2Cl(NHC) complexes, the increase in occupancy of the complete π-system of the carbene ligand upon coordination is lowest for the pyrido-annelated carbene and highest for the saturated carbene. Keywords: carbonyl complexes

• -parameter [25][26][27][28], the 13C NMR chemical shift of special Pd(NHC)2 complexes [29][30], and electrochemical properties [31][32][33] (see [34][35] for reviews). In all these cases, only the overall donor-abilities of the NHC ligand are obtained. In the case of the Tolman parameter, not only the

Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

• Anne L. Schöffler,
• Ata Makarem,
• Frank Rominger and
• Bernd F. Straub

Beilstein J. Org. Chem. 2016, 12, 1566–1572, doi:10.3762/bjoc.12.151

• Anne L. Schoffler Ata Makarem Frank Rominger Bernd F. Straub Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany 10.3762/bjoc.12.151 Abstract A dinuclear N-heterocyclic carbene (NHC) copper complex efficiently catalyzes azide–alkyne

• less time-consuming and more cost-efficient synthesis. Commercially available, inexpensive 4,5-dimethylthiazole is used as azole starting material instead of 4-aryl-1,2,4-triazoles. The precursor 1a for the NHC ancillary ligand is synthesized via a double SN2-reaction of two equivalents of thiazole

• characterized in our group [40]. The similarity of NMR-spectroscopic data of the 1,2,4-triazol-5-ylidene and the 1,3-thiazol-2-ylidene dicopper complex indicate that the complexes of both NHC ligand types consist of a bis-NHC ligand, two copper(I) ions and a labile acetate ligand that bridges the metal centers

Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

• Dirk Meyer and
• Thomas Strassner

Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150

• Dirk Meyer Thomas Strassner Physikalische Organische Chemie, TU Dresden, Bergstraße 66, 01062 Dresden, Germany 10.3762/bjoc.12.150 Abstract A series of methylpalladium(II) complexes with pyrimidine-NHC ligands carrying different aryl- and alkyl substituents R ([((pym)^(NHC-R))PdII(CH3)X] with X

• complexes were fully characterized by standard methods and in three cases also by a solid state structure. Keywords: alkane activation; alkyl complex; NHC; palladium; solid state structure; Introduction Palladium complexes have been shown to be versatile homogeneous catalysts in a variety of reactions [1

• byproduct of the methanol synthesis. Sen reported the activity of palladium(II) catalysts for the oxidation of methane [21] and several groups contributed to the progress in the field which is summarized in recent reviews [22][23]. The system based on N-heterocyclic carbene (NHC) ligands developed in our

Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions

• David C. Marelius,
• Curtis E. Moore,
• Arnold L. Rheingold and
• Douglas B. Grotjahn

Beilstein J. Org. Chem. 2016, 12, 1334–1339, doi:10.3762/bjoc.12.126

• dibasic complex 8. Keywords: NHC; 15N NMR spectroscopy; palladium; platinum; protic N-heterocyclic carbene; Introduction N-Heterocyclic carbenes (NHCs) have been extensively researched for a number of purposes since 1991 when Arduengo first isolated free NHCs [1][2][3]. NHCs as ligands have been known

• even longer. In 1968, Wanzlick and Öfele separately synthesized mercury(II) and chromium(0) imidazol-2-ylidene complexes [3]. Nearly 50 years of NHC ligand research have demonstrated the importance of the electronic and steric effects that can be modified by altering the alkyl or aryl groups on each

• , whereas for 4-PdCl, ∆ref = −13.1. This difference is likely due to a variety of factors related to the electronics of the nonprotic substituent of the PNHC and/or the ring size of the chelates, which is beyond the scope of this paper. For a given metal center and mono- or bis-NHC framework, we want to

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• copper(II) complexes were covalently linked to an engineered variant of the transmembrane protein Ferric hydroxamate uptake protein component A (FhuA ΔCVFtev). Copper(I) was incorporated using an N-heterocyclic carbene (NHC) ligand equipped with a maleimide group on the side arm at the imidazole nitrogen

• hydroxamate uptake protein component A (FhuA) as host for defined Cu(I) NHC or Cu(II) terpyridyl complexes with a maleimide moiety. By covalently bonding these copper complexes to the protein artificial Diels–Alderases based on a membrane protein have been obtained. Results and Discussion Synthesis of the

• contains a cysteine residue at position 545 for conjugation [31], an NHC ligand containing a maleimide function was prepared (Scheme 1). The imidazolium salt 3 was synthesized by nucleophilic substitution of mesityl imidazol 1 with maleimide derivative 2. These salts were used to generate the Cu(I) NHC

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• without significantly affecting the reaction (93–97% yield, 92:8 to 96:4 er). The authors also explored further elaboration of the products to access enantioenriched cysteine analogues. The Glorius lab has made use of N-heterocyclic carbene (NHC) catalysts for intermolecular Stetter reactions between

• aldehydes and α,β-unsaturated esters (Scheme 8) [25][26]. Catalyzed by triazolium NHC-catalyst 35, electron-poor and neutral aromatic aldehydes reacted with methyl 2-acetamidoacrylate to access α-amino esters 34a with excellent enantioselectivity [25]. As expected, less electrophilic 4-methoxybenzaldehyde

• that NHC’s possessing a 2,6-dimethoxyphenyl moiety led to both superior reactivity and selectivity, with catalyst 36 being optimal. Catalyst 35 provided the product in less than 5% yield. It was proposed that a more electron-rich, and thereby more nucleophilic, NHC was needed because the α-carbon

Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

• Shaojin Gu,
• Jiehao Du,
• Jingjing Huang,
• Huan Xia,
• Ling Yang,
• Weilin Xu and
• Chunxin Lu

Beilstein J. Org. Chem. 2016, 12, 863–873, doi:10.3762/bjoc.12.85

• imidazolium backbone and N substituents. The copper–NHC complexes tested are highly active for the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in an air atmosphere at room temperature in a CH3CN solution. Complex 4 is the most efficient catalyst among these polynuclear complexes in an air

• atmosphere at room temperature. Keywords: copper; CuAAC reaction; : N-heterocylic carbene; 1,2,3-triazole; Introduction N-Heterocyclic carbene (NHC) have interesting electronic and structural properties. This resulted in their use as versatile ligands in organometallic chemistry and homogeneous catalysis

• , reports concerning their preparation and use of 1,4-disubstituted-1,2,3-triazoles bearing NHC ligands are rare [22][23]. Elsevier et al. [23] reported several of palladium(II) complexes containing a heterobidentate N-heterocyclic carbene-triazolyl ligand. These palladium(II) complexes are active

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• derivatives by treatment with protecting groups in a one-pot reaction sequence. The reactivity of 1g has previously been well-exploited in catalytic borylation of aryl halides [22][23][24][25][26][27]. Herein, we report the C–H borylation of arenes using 1g catalyzed by an Ir/N-heterocyclic carbene (NHC

• C–H borylation [2], the reaction failed to give 2-B under these conditions (Table 1, entry 1). Several mono- and diphosphine ligands were found to be active for the formation of 2-B, but the best yield was only 21% (Table 1, entries 2–6). Our success in C–H borylation using NHC ligands [8][10] led

• us to investigate a series of NHC ligands for this process. Among the NHC ligands examined, 1,3-dicyclohexylimidazol-2-ylidene (ICy) [28][29][30][31][32][33] was found to be most effective, giving 2-B in 33% yield with a 2-/3-borylation ratio of 88:12 (Table 1, entry 9). It should be noted that [Ir

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

• the earliest known carbon–carbon bond-forming reactions catalysed by NHCs. The rapid growth of NHC catalysis in general has resulted in the development of a variety of benzoin and benzoin-type reactions. An overview of such NHC-catalysed benzoin reactions is presented. Keywords: acyloin reaction

• -heterocyclic carbenes (NHCs) are the two main classes of catalysts that are known to mediate benzoin reactions. This review focuses on the recent advancements made in the area of NHC-catalysed benzoin reactions. Historically, the first benzoin reaction was reported by Wöhler and Liebig in 1832. They discovered

• . Breslow postulated in 1958 a mechanistic rationale for the thiazolium salt-catalysed benzoin reaction [3]. He depicted the catalytically active species as a thiazolium zwitterion (the resonance structure of an NHC) and proposed that the reaction proceeds via an enaminol intermediate. The latter is now