A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• -step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions. Keywords: annulation; carbene; gold

• IPrAuCl [35]. In arylative cyclisations incomplete reaction was seen with enyne 19 [8][37] but ynone 22 [39] afforded high yield of 24. A quantitative conversion was seen in the intramolecular arylative cyclisation of 25 where 13 outperformed IPrAuCl [36]. Conclusion An L-shaped NHC ligand motif, AImOx

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• ) complex, [(IPr)CuCl] (Scheme 69). Hong and co-workers [92] developed diethylene glycol-functionalized imidazo[1,5,a]pyridin-3-ylidenes (DEG-ImPy) as a bifunctional NHC ligand. The Cu catalyst generated in situ with the DEG-ImPy·HCl salt 182 efficiently catalyzed direct C–H carboxylation of various

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• 10.3762/bjoc.19.65 Abstract We present here a stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles followed by trapping of the intermediate zinc enolate with carbocations. The use of a chiral NHC ligand provides chiral zinc

• . Results and Discussion For initial experiments, we have selected the conjugate addition of Me2Zn to acylimidazole 1a catalyzed by a chiral NHC ligand derived from imidazolium salt L1. This NHC precursor has been described previously by Gérard, Mauduit, Campagne and co-workers [19]. The ligand L1 is

• chiral NHC ligand L1 (3.36 mg, 0.0075 mmol, 3 mol %) were dissolved in freshly distilled anhydrous THF (1.0 mL) and the mixture was stirred for 10 min at rt. The reaction mixture was cooled to 0 °C, and then 1.6 M n-BuLi (12.5 µL, 0.02 mmol, 8 mol %) was added dropwise and the mixture was stirred for 10

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• styrenes 64 using a Ni–Al bimetallic system and NHC ligand 65 through intermolecular hydroarylation with high levels of enantio- and regioselectivity in the alkylated products 66 (Scheme 13). Also, the authors performed DFT studies revealing the reaction mechanism and supported that the interaction of the

• ]naphthyridine motifs 188 as desired products. Based on the experimental results and annulation chemistry a catalytic mechanism has been proposed (Scheme 36b) that involves the C3 hydrogen of pyridine undergoing a cyclorhodation with the catalyst in the presence of NaOAc, directed by in-built NHC ligand

• pyridine 195 and C4 pyridine 197 can undergo endo-cyclization reactions in the presence of Ni(cod)2, a chiral NHC ligand, and MAD as Lewis acid to afford optically active 5,6,7,8-tetrahydroquinolines 194 and 5,6,7,8-tetrahydroisoquinolines 196 and 198. The endo-selective annulation approach was compatible

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• backbones in the presence of Ag2O provided exclusively the three homomeric cylinders [Ag3(13)2]3+, [Ag3(14)2]3+, and [Ag3(15)2]3+ (state: SelfSORT-I in Figure 7). Upon the addition of gold(I) ions, a one-pot transmetalation triggered an exchange of the Ag+ ions for Au+ in the tris-NHC ligand-based cylinders

• ) [Co6(10')4]12+ and (b) [Co6(11')4]12+. (c) The 2-fold completive self-sorting after the addition of peripherally binding BPh4−. Exchange of Ag+ for Au+ ions in poly-NHC ligand-based organometallic assemblies. The reversible interconversion between the three-component rectangle [Cu4(16)2(17)2]4+ and the

Efficient [(NHC)Au(NTf₂)]-catalyzed hydrohydrazidation of terminal and internal alkynes

• Maximillian Heidrich and
• Herbert Plenio

Beilstein J. Org. Chem. 2020, 16, 2080–2086, doi:10.3762/bjoc.16.175

• alkynes (7a–j, 10 examples, 0.2–0.5 mol % [(NHC)Au(NTf2)], T = 60–80 °C) utilizing a complex with a sterically demanding bispentiptycenyl-substituted NHC ligand and the benign reaction solvent anisole, is reported. Keywords: alkyne; gold; homogeneous catalysis; hydrohydrazidation; NHC ligand

• = 60 °C, solvent chlorobenzene, reaction time 24 h, catalyst loading 0.2 mol %). The following conversions were observed: complex 1 >99%, complex 2 16%, complex 3 38%, complex 4 31%, and complex 5 60%. Complex 1 having a bispentiptycene-NHC ligand was the clear best among the five NHC-gold complexes

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• modulated through systematic variations of the steric and electronic design vectors of the NHC ligand [2]. These complexes have been used as highly efficient catalysts for a wide variety of C–C and C–X cross-coupling reactions [3]. Among others, different NHC–Pd complexes have been designed as efficient

• corresponding Pd–NHC complexes 4a and 4b (Scheme 1) were obtained by treatment of the supported imidazolium species with Pd(OAc)2 in the presence of a base. The amount of immobilized NHC ligand was determined by elemental analysis, while the palladium loaded on the polymer was determined by ICP analyses (see

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• = Br) led to the same three products in 22%, 10%, and 24% yields, respectively (Scheme 2). Later, a far higher yielding C–Si bond formation (66%) was developed by Hayashi [26]. More precisely, they used a catalytic amount of the complex formed from CuCl and NHC ligand L1, together with Suginome’s

• that α-amino esters could be obtained in excellent chemical yields with little erosion in enantiopurity. Similar work was described by Zhao et al. using a C1-symmetric chiral NHC ligand L6 together with catalytic amounts of CuCl. Here again, reactions could be performed on numerous albeit activated

• significantly. However, with the aniline derivative 69 (R = Ph on nitrogen), the ee dropped precipitously (Scheme 15). Chen et al. used a paracyclophane-based NHC ligand, along with Cu2O, to perform similar asymmetric 1,2-silyl additions onto activated imines. For several substrates (47) studied, the chemical

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• , Sapporo, Hokkaido 001-0021, Japan 10.3762/bjoc.16.50 Abstract A chiral phenol–NHC ligand enabled the copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters. The phenol moiety of the chiral NHC ligand played a critical role in producing the enantiomerically enriched products. The

• , while an achiral NHC/copper catalyst has successfully been utilized in this reaction [13]. Meanwhile, we devoted our effort to develop novel enantioselective C–C bond formation reactions utilizing chiral phenol–NHC/copper catalyst systems [14][15][16][17][18], in which the phenol group of the NHC ligand

• hydride species B. This transmetalation adds the silyl group to the phenoxy oxygen atom of the NHC ligand. The coordination of an α,β-unsaturated carbonyl compound 1 to the copper atom occurs in such a way that the bulky O-silyl group of the copper catalyst can avoid steric repulsions with the

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• ). A proposed reaction mechanism occurring via formation of a copper-acetylide species is proposed and illustrated in Scheme 8. The bis-NHC copper(I) complex 6 reacts with the alkyne leading to the formation of an acetylide derivative A (left hand side, Scheme 8), with concomitant loss of a NHC ligand

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• rearrangement and then successfully trapped with aryl bromides under palladium catalysis (Scheme 1). This system was extended to an asymmetric version using the chiral α-silyloxybenzylcopper(I) species having a chiral NHC ligand. In the asymmetric system, one example of allylic carbonate was used as the carbon

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• the ruthenium centre – “the upper” one is the N-heterocyclic carbene (NHC) ligand and “the lower” one is the 2-alkoxybenzylidene ligand. These determine the principal catalytic properties of the ruthenium complexes. Many ligands were tested as the upper part in various publications, which concluded

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• = 205 nM), affording ArM 2 (Scheme 13). From the different organometallic moieties tested, the catalyst containing 2,6-diisopropylphenyl groups on the NHC ligand afforded the highest activity for the aqueous RCM of N,N-diallyltosylamine (21). Metathase ArM 2 performed best in phosphate buffer at pH 5.0

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• towards the primary metathesis products tetradec-7-ene and ethene, outperformed the other complexes. In a computational study the improved catalytic performance was attributed to strengthening of the Ru–N bond due to steric repulsion between the substituted phenyl group and the NHC ligand [14]. An 8

• precatalysts when compared to 1 and 2 [10]. The pyridinyl-alcoholato Grubbs 2-types exhibited higher activities and selectivities than the Grubbs 1-types and were investigated in more detail. It is clear from the results that the chelating ability of the pyridinyl alcoholato ligands combined with the NHC

• ligand is responsible for the activity and improved stability of the precatalyst at high temperatures. In general 5d performed the best in the 1-octene metathesis reactions when compared to complexes 5a–c and 5e–h. The catalytic performance could be further tuned by the incorporation of an electron

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation

• Łukasz Gułajski,
• Andrzej Tracz,
• Katarzyna Urbaniak,
• Stefan J. Czarnocki,
• Michał Bieniek and
• Tomasz K. Olszewski

Beilstein J. Org. Chem. 2019, 15, 160–166, doi:10.3762/bjoc.15.16

• -heterocyclic carbene (NHC) ligand were revealed. The presented methodology allows for preparation of a variety of polar and non-polar metathesis products under environmentally friendly conditions. Keywords: catalysis; green chemistry; microwave; N-heterocyclic carbene; olefin metathesis; ruthenium; ultrasound

• . Additionally, under classical conditions, we observed a higher activity of catalyst 2a with Cl− as counter ion and a larger NHC ligand when compared to 1a. In turn, the use of US and μW had an inverse effect on that reaction furnishing lower yields of the product in the case of 2a when compared with 1a. In

• case of catalysts bearing a large hexafluorophosphate counter ion (PF6−; 1c and 2c) an increase of the NHC’s size had a negative effect on the catalyst performance (Table 2, entries 3 and 6, respectively). Examining further the influence of the steric hindrance of the NHC ligand we tested complexes 1a

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• and electronic properties of the NHC ligand. Significant advances in ruthenium metathesis catalyst design have been achieved by the introduction of unsymmetrically substituted NHC (uNHC) ligands, namely presenting different substituents at the nitrogen atoms. They offer the possibility of strongly

• N-fluorophenyl complexes the related [Rh(CO)2Cl(NHC)] complexes were synthesized. Unfortunately the shifts of the CO stretching frequencies showed that no correlation between the catalytic performances of Ru-catalysts and electronic properties of the corresponding NHC ligand is found. More recently

• activity of ruthenium-based complexes through enhanced electron-donating ability and different steric bulk of the NHC ligand. Mol et al. introduced complex 22 (Figure 6) in which one of the mesityl groups from GII-SIMes was replaced by the sterically more encumbered adamantyl group [19]. However, no

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• with E-alkenes (Ru-6) [6]. Furthermore, Pederson and Grubbs also demonstrated that diminishing the size of the ortho substitutents of the N-aryl groups of the NHC-ligand increased the efficiency for stereoretentive metathesis with E-alkenes (Ru-7 [3], Ru-8 [6], and Ru-9 [6]). It should be noticed that

• ]. A comprehensive computational study by Liu and Houk further validated this model, however, invoking distortion of the NHC ligand towards the dithiolate ligand as origin of the open pocket [13]. The proposed model assumes a side-bound mechanism, which results in a metallacycle perpendicular to the

• NHC ligand. To avoid steric repulsions, the substituents at the α-positions of the metallacycle point away from the N-aryl groups of the NHC-ligands. In contrast, the substituents at the β-position can point up or down. For the reaction with Z-alkenes (Figure 3a), the substituent at the β-position has

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• the existing commercial catalysts, playing mainly with the electronic characteristics of the ligands (usually two chlorides and an ylidene ligand) [15][16][17], whereas basically the sterics of the substituents on the N-heterocyclic carbene (NHC) ligand have remained unchanged [18]. Overall, any

• (1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene) and the IMes (1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) NHC ligands. The group trans to the NHC ligand is triphenylphosphine for all catalysts. Table 1 includes the energy profiles for the substituted indenylidenes, bearing methyl

• . Overall, among the catalysts with substituted indenylidene catalysts, the one bearing a SIMes NHC ligand and methyl groups in the indenylidene moiety is the most promising, in agreement with the experimental hypothesis that the release of the indenylidene ligand is more facile in such a case. The

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• catalyst as well as the ease of synthesis. In 2013 Kośnik and Grela performed a study to check the influence of the length of the spacer between the NHC ligand and the onium tag, by synthesizing the tag with an eight –(CH2)– linker [26]. The authors concluded that the extension of the linker does not

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• modification of the first coordination sphere by adding an N-heterocyclic carbene (NHC) ligand and a chelating styrene to the so-called Grubbs 1st generation catalyst, the relatively air- and moisture-stable Grubbs–Hoveyda type (GH-type) catalysts were obtained [7]. These catalysts do not only show stability

• synthesized by Ward [29]. A GH-type second generation olefin metathesis catalyst was modified at the periphery of an NHC ligand with a biotin moiety [46]. The small β-barrel protein avidin (Avi) or streptavidin (Sav) was incubated with the catalyst to give the artificial metalloprotein. This (strept)avidin

• NHC ligand. The conjugation was performed via maleimide-thiol “click” reaction under slightly basic (pH 7.5) conditions. Within the small cavity of NB4, only the GH-type catalyst Ru-6 with the longest spacer was able to undergo conjugation; however, the conjugational yield was very low (25%). Within

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• , whereas the IPr·HCl ligand provided tetrahydropyridoindoles 31 in reasonable regioselectivity (Scheme 22) [70]. Remarkably, the regioselectivity of the reaction is not only controlled by the steric effect of NHC ligand, but also depends on the olefin tether in 29. Recently, Petit and co-workers also

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• efficient suppression of the spectral broadening thanks to the bulky tert-butyl groups. Thus, “pure” blue electroluminescence with CIEy coordinate <0.1 and EQE of 17.2% were achieved for derivative 32 bearing a NHC ligand. Interestingly, upon increasing doping concentration from 2 to 6 wt % and employing

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• , we have developed an ortho C–H alkenylation reaction of pivalophenone N–H imines with alkenyl phosphates using a cobalt–NHC catalyst. The reaction takes place smoothly at room temperature and is applicable to a variety of substituted pivalophenone N–H imines and alkenyl phosphates. The NHC ligand