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

• storage form of otherwise unstable species [26][27], but proved also to be suitable starting materials for the generation of anionic NHCs by deprotonation. As examples of the latter mentioned species, sydnone anions 1 [28], imidazole-2-ylidene-4-olate 2 [29] as well as its 4-aminide derivatives [30] have

• bond angle of 177.35(8)° was found. However, in contrast to other gold complexes, the two imidazole rings are not coplanar [38]. In addition, the imidazole and the phenol rings are twisted about −119.84(16)° (C5–N1–C6–C7) relative to the imidazole ring. Two Au complexes are connected via one halide

• rhodium complex [41]. Correspondingly the Rh–O15 (202.49(14) pm) and Rh–O35 bond lengths cis to the shortened Rh–Ccarbene bond in 11 are identical (2.0244(14) pm), whereas the Rh–O55 bond trans to this bond is longer (209.98(15) pm). The phenolate rings are twisted in relation to the imidazole rings and

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• planned reaction sequence was the alkylating cyclisation of the liberated alcohols 8a–c to produce the indolizidine nucleus (Scheme 2). The cyclisation was achieved by initially treating these deprotected enaminones with imidazole and triphenylphosphine at ambient temperature in acetonitrile followed by

• conditions: (i) NH2(CH2)3OH, 250 °C (sealed tube), 18 h, 81%; (ii) Ac2O, pyridine, 0 °C, 10 min, then, rt, 18 h, 87%; (iii) Na2CO3, P2S5, THF, 5 h, 90%; (iv) BrCH2R, CH3CN, rt, 24 h; (v) PPh3, NEt3, CH3CN, 5 h; (vi) K2CO3, MeOH, rt, 3 h. Reagents and conditions: (i) Imidazole, PPh3, I2, CH3CN–PhCH3, reflux

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• dihydropyridine, hydantoin, imidazole, indole, isoquinoline, isoxazole, oxazole, 4H-pyran, pyrazine, pyridazine, pyridine, pyridinone, pyrimidine, pyrimidone, pyrrole, 3H-quinazolin-4-one, quinoline, 1H-quinolin-4-one, and thiophene. For heterocycles that are composed of a fused aromatic ring, such as

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• in the literature in comparison with monocyclic and fused derivatives [1][6]. Recently isoxazoles conjugated to pyrazole A [12], imidazole B [13] and tetrazole C [4] rings were found as promising candidates for anticancer and antidiabetic drugs and for the treatment of cognitive disorder (Figure 1

• -azolyl enamines bearing isoxazol-5-yl, imidazol-4-yl and imidazol-5-yl moieties with aryl, pyridyl and cyclohexylhydroxamoyl chlorides, pointing to a concerted mechanism of this reaction. Results and Discussion The starting enamines 1a–e bearing imidazole (1a,b) and isoxazole (1c–e) rings were prepared

• the products due to the formation of a large amount of tar-like products. Enamines 1a–e, bearing imidazole and isoxazole rings and several hydroxamoyl chlorides 2a–h bearing aryls with electron-withdrawing and releasing groups, pyridine and cyclohexane can be used for the synthesis of azolylisoxazoles

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• cultures were cooled down to 18 °C. After incubation overnight (160 rpm, 18 °C), cells were harvested by centrifugation (5000g, 4 °C, 45 min) and resuspended in binding buffer (20 mL; 20 mM Na2HPO4, 0.5 mM NaCl, 20 mM imidazole, 1 mM MgCl2, pH 7.0). The cells were crushed by ultra-sonification (6 × 1 min

• , 0.5 M imidazole, 1 mM MgCl2, pH 7.0) and used directly for incubations with 5 mg of (1R)- and (1S)-(1-2H)GPP, solved in incubation buffer (50 mM Tris/HCl, 10 mM MgCl2, 20% v/v glycerol, pH 8.2) to reach a final substrate concentration of 0.2 mg/mL. The enzyme reaction was incubated for 2 h at 28 h

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• concentration of only 1–5 mol %, and the target molecule was quantitatively obtained in 30 min at 74 °C, by using 3.2 equivalents of DMC with respect to glycerol. As the BMIM-2-CO2 catalyst is synthesized starting from butyl-imidazole and DMC (Scheme 10), the authors also attempted to combine the in situ

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

• the conjugated 14 πe− system that thus allows for an enhanced Rh–CO backbonding. This extremely low π-acceptor ability is also corroborated by the 77Se NMR chemical shift of −55.8 ppm for the respective selenourea, the lowest value ever measured for imidazole derived selenoureas. DFT-calculations of

• carbenes derived from imidazole so far. This overcompensates even the lower σ-donor character, so that their overall electron-donating ability lies in between that of acyclic diaminocarbenes and saturated NHCs. Results and Discussion Synthesis of the rhodium CO and 13CO complexes 2a and 2b We generated the

• respective selenourea 4b to be −55.8 ppm [77]. This value is the most negative reported so far for imidazole derived selenoureas and therefore, is another hint for the unusually low π-accepting quality of the dipyridocarbene family dipiy. To rationalize these strong overall donating properties we performed

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• ; 20 mM Na2HPO4, 0.5 M NaCl, 20 mM imidazole, 1 mM MgCl2, pH 7.0). The disruption of the cells was done by ultra-sonication on ice for 8 × 60 s for each portion of cells from 2 L of culture. The soluble enzymes were harvested at 4 °C and 11000 rpm by centrifugation (2 × 10 min). Protein purification

• was performed by Ni2+-NTA affinity chromatography with Ni2+-NTA superflow (Novagen) using binding buffer and elution buffer (20 mM Na2HPO4, 0.5 M NaCl, 0.5 M imidazole, 1 mM MgCl2, pH 7.0). Incubation experiments were performed with the pure protein fractions and the natural substrate FPP (amount and

• -epi-α-eudesmol synthase and (6-13C)FPP, the soluble enzyme fraction was washed with binding buffer (20 mM Na2HPO4, 0.5 M NaCl, 20 mM imidazole, 1 mM MgCl2, pH 7.0 in 2H2O) and then eluted twice with 10 mL elution buffer (20 mM Na2HPO4, 0.5 M NaCl, 0.5 M imidazole, 1 mM MgCl2, pH 7.0 in 2H2O). Each

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• (Figure 7). In the case of substrate 40 precipitation occurred as soon as the two solutions came into contact at the T-piece mixer, which was probably due to strong coordination to the copper acetate by the imidazole ring. This made running this reaction problematic in flow due to the occurrence of

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• aromatic imidazole. Therefore, we envisioned that a ketone-involved reaction could proceed, if the [4 + 1] cycloaddition adduct can further rearrange to form an aromatic imidazole. With this idea in mind, we started to study an isatin-involved GBB reaction [38][39], because the resulting [4 + 1

• functional group. A further intramolecular nucleophilic reaction of the imidazole and the newly generated isocyanate provides the final product 1. Noteworthy, the benzodiazepinone-fused imidazo[1,2-a]pyridine 5 was not observed which may be due to the strain of the seven-membered ring. Conclusion In

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• compound high flexibility. Initially reported by K. Seley-Radtke’s group, the replacement of the nucleobase by a “flexi-moiety” where the imidazole ring and a six-membered heterocycle is linked through a C–C bond lead to new derivatives behaving as nucleosides and even as enzyme inhibitors [11][12][13

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• , 2.4 mmol) in diethyl ether (30 mL) under nitrogen. The reaction was quenched after 24 hours by the addition of imidazole (0.4 g, 6 mmol), and the resulting cloudy solution was washed with saturated aqueous NaHCO3 (200 mL), filtered and extracted with diethyl ether (3 × 50 mL). The combined organic

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• centrifugation at 4 °C and 3600 rpm for 45 minutes, resuspension in 20 mL binding buffer (20 mM Na2HPO4, 0.5 M NaCl, 20 mM imidazole, 1 mM MgCl2, pH 7.0) and cell disruption by ultra-sonication on ice for 4 × 60 s followed by centrifugation at 4 °C and 11000 rpm, yielded in the soluble enzyme fraction. Protein

• purification was performed by Ni2+-NTA affinity chromatography with Ni2+-NTA superflow (Novagen) using binding buffer and elution buffer (20 mM Na2HPO4, 0.5 M NaCl, 0.5 M imidazole, 1 mM MgCl2, pH 7.0). Incubation experiments were performed with the pure protein fractions (checked by SDS-PAGE) and all fifteen

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple

• –imidazole polyamides; sequence specificity: DNA; triplex-forming oligonucleotides; Introduction The recognition and detection of specific sequences in native genomic double-stranded DNA (dsDNA) is of significant importance for the development of efficient gene therapies and in vivo gene labeling [1][2][3

• ]. Besides natural and engineered peptides or proteins, two synthetic substances are known to recognize and bind dsDNA in a sequence-specific manner: triplex-forming oligonucleotides (TFOs) [4][5] and pyrrole–imidazole polyamide minor groove binders (MGBs) [6][7]. TFOs recognize polypurine stretches in

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

• for 6-Pd) shows strain in the Pd1–N1’ (and Pd1’–N1) bond. This is due to the metal that remains in the plane defined by the three coordinating atoms of the tridentate ligand (i.e., C1, N3, and C4). The fourth donor atom from the other has to bend out of the plane with the N1’ imidazole ring because of

• the adjacent sterics of the tert-butyl groups on the imidazole. The strain can be quantified by examining how far the metal is from the N1 (or N1’)-bound imidazole plane (C1–C2–C3–N1–N2 plane and the symmetry-equivalent atoms): for 6-Pd, 1.241 Å and, for 6-Pt, 1.094 Å (Table 1). Further evidence is

• -PtCl, the NH proton resonance is typically downfield shifted with a chemical shift of ca. 11 ppm, whereas this signal is strongly shifted upfield to 8.03 (6-Pd) or 8.19 ppm (6-Pt). The crystal structures for both 6-Pd and 6-Pt show that the NH is located above the pi system of one imidazole ring of the

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

• procedures. Syntheses Synthesis and characterization of IMesBr 3 A solution of 1-(3-bromopropyl)-1H-pyrrol-2,5-dione (1.69 g, 7.75 mmol, 1.00 equiv) and 1-(mesityl)-1H-imidazole (1.66 g, 8.91 mmol, 1.10 equiv) in toluene (35 mL) was stirred in a closed Schlenk tube for 24 h at 110 °C. The colorless

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• ’ starting material its reaction with vinylmagnesium bromide afforded racemic 3° allylic alcohol rac-68 in an 88% yield. Subsequent hydroxy group protection using tert-butyldimethylsilyl chloride and imidazole afforded orthogonally protected O-TBDMS/PMB ether rac-69 in a moderate 53% yield. Needless to say

Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives

• Larisa Yu. Gurskaya,
• Diana S. Belyanskaya,
• Dmitry S. Ryabukhin,
• Denis I. Nilov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 950–956, doi:10.3762/bjoc.12.93

• of compounds 5 and 6 with arenes in TfOH were checked. Analogously to other heteroaromatic aldehydes of the series of pyridine [19], quinolone [20], pyrazol [21], and imidazole [22], the superelectrophilic activation of the formyl group in 5 was expected. Indeed, compounds 5a,b and d reacted with

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

• pyrimidyl-imidazole complex [32]. However, a red binuclear Cu(I) complex 3 was obtained in 57% yield when we reacted pyrimidyl benzimidazolium salt 1b with copper powder. Furtherly, we got a yellow Cu(I)–NHC complex 4 in about 70% yield from pyridine imidazolium salt 1c and copper powder (Scheme 1). In

• ) at 50 °C for 10 h, orange yellow solid. Yield: 71 mg, 68%. 1H NMR (600 MHz, acetonitrile-d3) δ 7.96 (s, 1H, triazole), 7.90 (br, 1H, 2-py), 7.83 (br, 1H, imidazole), 7.76 (s, 1H, 4-py), 7.57 (br, 1H, imidazole), 7.41 (s, 1H, 5-py), 7.37 (d, J = 7.8 Hz, 3H, phenyl), 7.30–7.22 (m, 3H, phenyl + 3-py

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• 2 and 3, the morpholine ring was replaced by a 3-methyl-1,2,4-oxadiazole ring [44]. Whereas 2 maintains the linezolid C5 side chain, compound 3 is substituted by a imidazole-1-yl. With its MIC value of 2 mg/L compound 2 seems to be comparable (or even more effective against the MRSA 433 strain, see

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• by reacting β-CD with tosyl imidazole (TsIm) [15]. Great advantages, in terms of yields, reaction times and product purity, were obtained by using a cavitating tube (40 min, 19.2 kHz, 20 W, yield: 55%). Thanks to the fast US-assisted inclusion complex formation between β-CD and TsIm reaction times

• performed in the presence of tosyl imidazole and molecular sieves under US irradiation. As shown in Table 1, the reaction time was shortened to 2 h for α-CD (yield: 36%), 1 h for β-CD (yield: 40%) and 45 min for γ-CD (yield: 46%) (Scheme 4) [21]. In Table 1 we compared the preparation of several

• . Synthesis of 6I-(p-toluenesulfonyl)-β-CD. Example of CuAAC with 6I-azido-6I-deoxy-β-CD and phenylacetylene. Synthesis of 6I-benzylureido-6I-deoxy-per-O-acetyl-β-CD. Synthesis of 3I-azido-3I-deoxy-altro-α, β- and γ-CD. Synthesis of 2-2’ bridged bis(β-CDs). Reaction conditions: 1) TBDMSCl, imidazole, dry

Highly stable and reusable immobilized formate dehydrogenases: Promising biocatalysts for in situ regeneration of NADH

• Barış Binay,
• Dilek Alagöz,
• Deniz Yildirim,
• Ayhan Çelik and
• S. Seyhan Tükel

Beilstein J. Org. Chem. 2016, 12, 271–277, doi:10.3762/bjoc.12.29

• NaCl, 5 mM imidazole) at 4 °C. Then, the cells were disrupted by sonication and the sonicated cells were harvested by centrifugation (28000 × g, 30 min) at 4 °C. The cell pellet was resuspended in an ice-cold buffer (20 mM NaH2PO4, 0.5 M NaCl, 30 mM imidazole, pH 7.4). The resuspended cells were

• mL of elution buffer (20 mM phosphate buffer, 0.5 M NaCl with 100 mM imidazole pH 7.4), 5 mL of elution buffer (20 mM phosphate buffer, 0.5 M NaCl with 0.2 M imidazole pH 7.4), and finally 3 mL of elution buffer (20 mM phosphate buffer, 0.5 M NaCl with 0.4 M imidazole pH 7.4). The collected fractions

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• Schemes 5–10, the CD ring is drawn as in Figure 6 for β-CD and TRIMEB. This representation was also chosen for their derivatives in order to point out the modified units. Modifications at the C-6 positions Synthesis: In 1989, Breslow and Anslyn [73] described the synthesis of a bis(imidazole)-β-CD

• of DIBAL-H to produce 2A,3B-diol 46 from TRIMEB (Scheme 9) [90]. The two remaining free alcohols were then functionalized with the α-nucleophile and an imidazole group [88]. The acid–base dyad thus obtained is likely to improve the hydrolysis of nerve agents. The imidazole group was first introduced

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• CUGexp, also binding CUGexp that slips through inhibiting its sequestration of MBNL1, and, with the catalytic amino/ammonium/imidazole groups, slowly cleaving the CUG-RNA to prevent RAN translation [92]. Edwin Chan and his group again studied the in vivo activity of our compounds, showing that 32

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

• ; 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

• ) centre, shows that the effect on system 3 of the released electron is mainly paid by the metal centres, but also partially spread over the ligands [59]. To follow up the experimental results the tautomerism/metallotropism between pNHC and imidazole ligands in these iridium complexes bearing a doubly C,N