Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• . It has been achieved in the past for example by Francis and co-workers and Ball and co-workers using rhodium-catalyzed carbene-insertion reactions [21][22][23] or via direct C–H arylation [24][25][26][27][28][29]. If the installation of alkynes on peptides or proteins is desired, an indirect method

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

• borylation; iridium; N-heterocyclic carbene; Introduction Catalytic C–H borylation of arenes has become an essential tool in organic synthesis [1]. The eminent features of this methodology include 1) no directing group is needed, allowing the direct functionalization of simple arenes; 2) the

• 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

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

• nucleophile and then as a leaving group in cyanide-catalysed benzoin reactions [8]. Analogously, Breslow invoked the generation of a nucleophilic thiazolylidene species 1 via deprotonation of the thiazolium salt by base. The ylide 1 may also be represented as its resonance structure 1’ (carbene). Nucleophilic

• may be regarded as the first report of an NHC-catalysed benzoin reaction on a synthetically useful scale [9]. Much later, in 2005, Xu and Xia used N-alkyl-substituted imidazolium carbene 6 to efficiently promote benzoin reactions. Although a high catalyst loading (50 mol %) was required, the reactions

Scope and limitations of the dual-gold-catalysed hydrophenoxylation of alkynes

• Adrián Gómez-Suárez,
• Yoshihiro Oonishi,
• Anthony R. Martin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2016, 12, 172–178, doi:10.3762/bjoc.12.19

• in unsymmetrical alkynes can help to achieve high regioselectivity in the hydrophenoxylation. Keywords: cooperative catalysis; gold catalysis; hydrophenoxylation; N-heterocyclic carbene; vinyl ethers; Introduction During the last 30 years, N-heterocyclic carbenes (NHCs) have evolved from mere

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• -heterocyclic carbene bearing precursor complexes M31, HovII or M32 with excess of 5,7-dichloro-8-hydroxyquinoline or 5,7-dibromo-8-hydroxyquinoline in the presence of excess Cs2CO3 as the base (see Scheme 1). The silver-free method [41] resulted in any case in the formation of at least two new products (as

• ppm in 3) when the N-heterocyclic carbene ligand is situated trans to the N-atom of the quinolinolate. The corresponding proton of the second quinolinolate ligand (with the N-atom situated cis to the NHC) is high-field shifted and resonates at 5.48 (in 1b), 5.32 (in 2b) and 5.9 (in 4). The OC-6-14

• the initiators was investigated. For that purpose, 4 was mixed with 5 equiv of monomer 5 in CDCl3 and activated it with 5 equiv of etherical HCl in a NMR tube. After few minutes, the characteristic carbene peak for propagating alkylidenes at 18.1 ppm appeared (see Figure 3). To identify this carbene

Versatile deprotonated NHC: C,N-bridged dinuclear iridium and rhodium complexes

• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 117–124, doi:10.3762/bjoc.12.13

• Albert Poater Institut de Química Computacional i Catàlisi, Departament de Química, Universitat de Girona, Campus de Montilivi, E-17071 Girona, Spain 10.3762/bjoc.12.13 Abstract Bearing the versatility of N-heterocyclic carbene (NHC) ligands, here density functional theory (DFT) calculations

• ; iridium; isomerization; N-heterocyclic carbene; rhodium; Introduction In the framework of organometallic chemistry, N-heterocyclic carbenes (NHC) centre a well stablished class of relatively new ligands since in 1991 Arduengo and collaborators isolated the first stable NHC of the imidazole type with

• exhibit better activity, despite bearing its carbene functionality. Of course, these good results in basic research supposed and explosion of industrial efforts to design the right metal NHC-based catalyst for any kind of reaction. Anyway, neither a unique nor a few list of catalysts turned out to be

N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd–NHC complexes: synthesis, characterization and catalytic activity in carbon–carbon bond-forming reactions

• Senem Akkoç,
• Yetkin Gök,
• İlhan Özer İlhan and
• Veysel Kayser

Beilstein J. Org. Chem. 2016, 12, 81–88, doi:10.3762/bjoc.12.9

• , 44280 Malatya, Turkey 10.3762/bjoc.12.9 Abstract A series of novel benzimidazolium salts (1–4) and their pyridine enhanced precatalyst preparation stabilization and initiation (PEPPSI) themed palladium N-heterocyclic carbene complexes [PdCl2(NHC)(Py)] (5–8), where NHC = 1-(N-methylphthalimide)-3

• with 4-chlorotoluene. Keywords: arylation; benzimidazolium salts; catalysis; N-heterocyclic carbene; PEPPSI complex; Suzuki–Miyaura cross-coupling reaction; Introduction The use of N-heterocyclic carbenes (NHCs) as ligands was started by Wanzlick [1] and Öfele [2] almost fifty years ago. There have

• been major advances in the design and synthesis of metal complexes containing N-heterocyclic carbene ligands in the last two decades, and they had a wide range of applications in different fields, particularly in homogeneous/heterogeneous catalysis [3][4][5][6][7][8] and bioorganometallic chemistry [9

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• catalyst bearing a modified N-heterocyclic carbene ligands is reported. The new catalyst contains an NHC ligand symmetrically substituted with chromanyl moieties. The complex was tested in model CM and RCM reactions. It showed very high activity in CM reactions with electron-deficient α,β-unsaturated

• compounds even at 0 °C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify. Keywords: chromane derivatives; metathesis catalyst; nitrogen heterocycles; olefin metathesis; Ru-carbene; Introduction Olefin metathesis is

• of organic chemistry since 1992, when Grubbs discovered the first well-defined ruthenium catalyst [2]. Nearly 400 ruthenium heterocyclic carbene-coordinated olefin metathesis catalysts were prepared until 2010 [3]. Since 2011, when Grubbs reported the synthesis of a Z-selective catalyst [4], several

Pyridylidene ligand facilitates gold-catalyzed oxidative C–H arylation of heterocycles

• Kazuhiro Hata,
• Hideto Ito,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2015, 11, 2737–2746, doi:10.3762/bjoc.11.295

• strongest electron-donating N-heterocyclic carbenes, resulted in the rate acceleration of the C–H arylation reaction of heterocycles over conventional ligands such as triphenylphosphine and a classical N-heterocyclic carbene. In situ observation and isolation of the 2-pyridylidene-gold(III) species, as well

• as a DFT study, indicated unusual stability of gold(III) species stabilized by strong electron donation from the 2-pyridylidene ligand. Thus, the gold(I)-to-gold(III) oxidation process is thought to be facilitated by the highly electron-donating 2-pyridylidene ligand. Keywords: carbene ligand; C–H

• numerous benefits such as high activity and stability of gold catalyst, thereby achieving otherwise-difficult oxidative transformations [37][38][39][40]. Recently, we have introduced highly electron-donating triaryl-2-pyridylidene (PyC: pyridine-based carbene) [82][83][84] as a new type of nonclassical N

Direct estimate of the internal π-donation to the carbene centre within N-heterocyclic carbenes and related molecules

• Diego M. Andrada,
• Nicole Holzmann,
• Thomas Hamadi and
• Gernot Frenking

Beilstein J. Org. Chem. 2015, 11, 2727–2736, doi:10.3762/bjoc.11.294

• calculations and with an energy decomposition analysis. The investigated molecules include N-heterocyclic carbenes (NHCs), the cyclic alkyl(amino)carbene (cAAC), mesoionic carbenes and ylide-stabilized carbenes. The bonding analysis suggests that the carbene centre in cAAC and in diamidocarbene have the

• size of the backbone ring [39][40][41], variation of the α-heteroatoms [7], anti-Bredt NHCs [42][43], mesoionic NHCs [44][45][46][47], ylide stabilized carbenes [48][49][50][51] and other [52][53][54][55]. A remarkable variation was introduced with the cyclic alkyl(amino)carbene (cAAC) by Bertrand in

• 2005 [20][56][57]. The replacement of one amino substituent by a saturated alkyl group makes the carbene more nucleophilic and electrophilic at the same time [20][56][57]. Since then, cAACs have been used as a superior ligand for the stabilization of unstable chemical species, radical and main group

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• microreactor, a new protocol for scalable aromatic trifluoromethylation was developed. From a mechanistic aspect, Vicic and co-workers explored the direct generation of CF3Cu from CF3CO2Cu. The use of (N-heterocyclic carbene)copper-trifluoroacetates prepared from trifluoroacetic acid (TFA) was investigated in

Rhodium, iridium and nickel complexes with a 1,3,5-triphenylbenzene tris-MIC ligand. Study of the electronic properties and catalytic activities

• Carmen Mejuto,
• Beatriz Royo,
• Gregorio Guisado-Barrios and
• Eduardo Peris

Beilstein J. Org. Chem. 2015, 11, 2584–2590, doi:10.3762/bjoc.11.278

• , Portugal 10.3762/bjoc.11.278 Abstract The coordination versatility of a 1,3,5-triphenylbenzene-tris-mesoionic carbene ligand is illustrated by the preparation of complexes with three different metals: rhodium, iridium and nickel. The rhodium and iridium complexes contained the [MCl(COD)] fragments, while

• the nickel compound contained [NiCpCl]. The preparation of the tris-MIC (MIC = mesoionic carbene) complex with three [IrCl(CO)2] fragments, allowed the estimation of the Tolman electronic parameter (TEP) for the ligand, which was compared with the TEP value for a related 1,3,5-triphenylbenzene-tris

• and 3 were characterized by NMR and mass spectrometry. Both, the 1H and the 13C NMR spectra of the complexes were consistent with the expected threefold symmetry of the molecules, as exemplified by the appearance of one only signal for the carbene carbons, at 173.4 (1JRh–C = 41.5 Hz) and 172.1 ppm

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• and feature strongly electron-donating and sterically bulky phosphine or N-heterocyclic carbene (NHC) ancillary ligands [6][7]. In particular, precatalysts of the type (η3-allyl)Pd(NHC)(Cl) have shown excellent activity for the Suzuki–Miyaura reaction, with systems incorporating an η3-cinnamyl moiety

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• derivatives, whereas the use of triethyl orthoformate under microwave irradiation was most appropriate for the fast and efficient synthesis of imidazolinium salts. This strategy was applied to the synthesis of six common N-heterocyclic carbene precursors, namely, 1,3-dimesitylimidazolium chloride (IMes·HCl

• serves de facto as a carbene source for most catalytic and synthetic purposes. Alternative methods to generate NHCs without the intervention of a base, which might lead to unwanted side-reactions, include the facile cleavage of NHC·CO2 zwitterions (Scheme 1, path B) [31][32][33][34][35], the thermolysis

• scattered in the literature, often relegated to supporting information, and comparison of their respective merits has become more and more challenging. In this report, we aimed at collecting a series of efficient synthetic protocols for the preparation of eight common N-heterocyclic carbene precursors

Evidencing an inner-sphere mechanism for NHC-Au(I)-catalyzed carbene-transfer reactions from ethyl diazoacetate

• Manuel R. Fructos,
• Juan Urbano,
• M. Mar Díaz-Requejo and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2015, 11, 2254–2260, doi:10.3762/bjoc.11.245

• Abstract Kinetic experiments based on the measurement of nitrogen evolution in the reaction of ethyl diazoacetate (N2CHCO2Et, EDA) and styrene or methanol catalyzed by the [IPrAu]+ core (IPr = 1,3-bis(diisopropylphenyl)imidazole-2-ylidene) have provided evidence that the transfer of the carbene group

• CHCO2Et to the substrate (styrene or methanol) takes place in the coordination sphere of Au(I) by means of an inner-sphere mechanism, in contrast to the generally accepted proposal of outer-sphere mechanisms for Au(I)-catalyzed reactions. Keywords: carbene transfer; inner sphere; gold catalysis; O–H

• . Most of the reported systems contain an unsaturated fragment that is activated upon coordination to the gold center, thus triggering further transformations, the formation of very reactive gold–carbene intermediates being proposed [4][5][6][7][8][9][10][11][12][13][14]. As a representative example, the

Copper catalysis in organic synthesis

• Sherry R. Chemler

Beilstein J. Org. Chem. 2015, 11, 2252–2253, doi:10.3762/bjoc.11.244

• been published in 2014. In point of fact, there has been a steady increase in publications on this topic since 1988. In the late 1980’s and early 1990’s, the topics centered on copper nitrene reactivity (e.g., aziridination), copper carbene chemistry, conjugate additions and cross-coupling reactions

Half-sandwich nickel(II) complexes bearing 1,3-di(cycloalkyl)imidazol-2-ylidene ligands

• Johnathon Yau,
• Kaarel E. Hunt,
• Laura McDougall,
• Alan R. Kennedy and
• David J. Nelson

Beilstein J. Org. Chem. 2015, 11, 2171–2178, doi:10.3762/bjoc.11.235

• prepared [Ni(η1-Cp)(η5-Cp)(IMes)] (1) from the reaction of the free carbene with nickelocene (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) (Scheme 1a) [9]. Complexes of the form [NiCl(Cp)(NHC)], such as complex 2, are typically prepared by simply heating nickelocene with the corresponding

• reactions. The reactions were conducted in duplicate, and were analysed by 1H NMR methods to calculate conversion. The new ICy- and IDD-bearing complexes were benchmarked against [NiCl(Cp)(IPr)] (5) due to the ubiquity of this carbene in transition metal-mediated catalysis [29][30], and [NiCl(Cp)(IPr*)] (6

Computational study of productive and non-productive cycles in fluoroalkene metathesis

• Markéta Rybáčková,
• Jan Hošek,
• Ondřej Šimůnek,
• Viola Kolaříková and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2015, 11, 2150–2157, doi:10.3762/bjoc.11.232

• the non-productive cycle (Figure 3). The difference in the stability of the corresponding complexes a2j and s2j can be explained partially by the π-donation of difluoromethylene carbene in analogy to [37], but also by the electron donation of the π-bond of the 1,1-difluoroethene (2) molecule with a

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• -workers synthesized the first well-defined ruthenium(II) complex (5, Scheme 2) bearing a carbene moiety, able to perform ring-opening metathesis polymerization (ROMP) reactions of low-strained olefins [34][35] and ring-closing metathesis (RCM) reactions of functionalized dienes [36]. In the solid state

• heteroleptic complexes, bearing one N-heterocyclic carbene (NHC) (16–19, Figure 1) and one phosphine as ligands, represented the second crucial turning point in this chemistry. Following Herrmann’s report on bis-NHC ruthenium complexes (10–15) and their low activity [39], independently and simultaneously the

• Grela group presented some variations of the Hoveyda–Grubbs catalyst 21 [52][59][60]. They reported some modifications to the isopropoxystyrene group; a nitro group para to the isopropoxy moiety of the carbene provided a much faster initiating catalyst (87, Figure 12) than 21, due to the weakening of

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• ]. The ROMP and RCM performance of Fischer-carbene complexes such as 9 are often sluggish and often do not result in high conversions [65][66]. However, these complexes are thermally very inert and economically viable options to other commercially available olefin metathesis catalyst. Furthermore, their

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties

• Laura G. Sarbu,
• Lucian G. Bahrin,
• Peter G. Jones,
• Lucian M. Birsa and
• Henning Hopf

Beilstein J. Org. Chem. 2015, 11, 1917–1921, doi:10.3762/bjoc.11.207

• involves the conversion of 2-N,N-dialkylamino-1,3-dithiolium salts into the corresponding 2-unsubstituted 1,3-dithiolium salts, followed by the homocoupling of the carbene intermediate that is generated under basic conditions. Unfortunately, our attempts to synthesize the 2-unsubstituted derivative from

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• . Furthermore, this transformation should be considered as a two-step reaction where the ring-opening metathesis (ROM) is the initial step followed by a CM. It is well known that oxanorbornenes (e.g., 1 and 2) are generally excellent substrates for ROCM reactions [14]. The cycloaddition of the ruthenium carbene

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• recent applications, metathesis has also been used in chemical biology, either in the form of an artificial metalloenzyme [8][9][10] or for the post-translational modification of proteins [11]. To address these various challenges, a vast number of carbene complexes based on different transition metals

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• have covered literature that appeared during the last seven years (2008–2014). Keywords: Diels–Alder chemistry; green chemistry; natural products; olefin metathesis; polycycles; ring-rearrangement metathesis; Introduction Transition metal–carbene complexes (Figure 1) introduced during the last two

• with the aid of a carbene insertion reaction. Further, this cyclopropene system 16 was subjected to RRM in the presence of catalyst 1 to generate 3-pyrroline derivatives 18a,b using simple starting materials in a single step (Scheme 1). A wide range of heterocycles have been assembled by RRM. When a

• % yield [51]. The regioselective formation of 240 may be attributed to the facile formation of a Ru–carbene intermediate where the metal participates on the side opposite to that of the methyl ester and thereby minimizing the steric crowding between ruthenium and carbonyl oxygen of an ester functionality

Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis

• Alba Collado,
• Scott R. Patrick,
• Danila Gasperini,
• Sebastien Meiries and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 1809–1814, doi:10.3762/bjoc.11.196

• ) complexes of the formula [Au(NHC)(NTf2)] (NHC = N-heterocyclic carbene) bearing bulky and flexible ligands have been synthesised. The ligands studied are IPent, IHept and INon which belong to the ‘ITent’ (‘Tent’ for ‘tentacular’) family of NHC derivatives. The effect of these ligands in gold-promoted