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

• temperature for the stated time, then filtered and concentrated. The resulting residue was analyzed by 1H NMR to determine the conversion. Subsequently, the residue was eluted from a column of silica gel with 20:1 cyclohexane–AcOEt to give isolated 3aa. Procedure for the model Stetter-like reaction under

• resulting residue was analyzed by 1H NMR to determine the conversion. Subsequently, the residue was eluted from a column of silica gel with 13:1 cyclohexane–AcOEt to give isolated 10aa. Trapping experiment (Scheme 2) A mixture of benzil (1a, 210 mg, 1.00 mmol), PS-BEMP 5 (454 mg, 1.00 mmol) and DMF (2 mL

• ) was stirred at 50 °C for 30 min then acetic anhydride (0.94 mL, 10.0 mmol) was added in one portion. The reaction mixture was stirred at 50 °C for 2 h, then cooled to room temperature, filtered, concentrated, and eluted from a column of silica gel with 7:1 cyclohexane–AcOEt to give (Z)-1,2

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• diluted with dichloromethane (10 mL) and washed with saturated sodium bicarbonate solution (10 mL). The organic layer was then dried over Na2SO4 and evaporated, and the resulting crude product was purified by flash chromatography (50% ethyl acetate in cyclohexane, size: 19.0 × 1.5 cm, 15 g silica gel

• ). Yield: 73 mg (44%) of compound 8 as white foam. TLC (50% ethyl acetate in cyclohexane): Rf = 0.56; 1H NMR (300 MHz, DMSO-d6) δ 0.74–0.95 (m, 48H, NCHN(CH2CH2CH2CH3)2a,b), Si(CH(CH3)3)3a,b), 1.12–1.23 (m, 24H, N(CH(CH3)2)2a,b), 1.28–1.36 (m, 8H, NCHN(CH2CH2CH2CH3)2a,b), 1.55–1.60 (m, 8H, NCHN

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• evaporation. A fraction of crude product was then purifiied through silica column chromatography (EtOAc/cyclohexane (40:1), Rf: 0.6). Molecular formula: C17H29BrO. 1H NMR (400 MHz, CDCl3, 298 K) δ 3.33 (m, 4H, 1,6-H), 2.88 (s, 2H, 7-H), 1.89 (p, J = 3.1 Hz, 3H, 10-H), 1.84–1.75 (m, 2H, 2-H ), 1.68–1.55 (m, 6H

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

• , catalytic hydration of cyclohexene, or catalytic air oxidation of cyclohexane. However, as an intellectual exercise and proof of principle, we may be able to use the results described for integer partitioning to devise creative syntheses for cyclohexanone which involve actual ring construction via 2

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

• 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

The weight of flash chromatography: A tool to predict its mass intensity from thin-layer chromatography

• Freddy Pessel,
• Jacques Augé,
• Isabelle Billault and
• Marie-Christine Scherrmann

Beilstein J. Org. Chem. 2016, 12, 2351–2357, doi:10.3762/bjoc.12.228

• column using as eluent a 7:3 cyclohexane–acetone mixture (Table 2, entry 1). The mass fraction of product in the crude reaction mixture (79%) was calculated after chromatography taking into account the isolated mass of 1. The values calculated using Equation 18 with N = 35 or Ncalc (Equation 16, B

• = 33.64 or B = 51.70) deviated only from 6, 7 and 11% of the experimental value, respectively. Another experiment (a(bis), Table 2, entry 2) led to a crude reaction mixture containing 60% by weight of 1 which was purified using a disposable cartridge (PuriFlash SIHP 30 µm, Interchim) and cyclohexane–AcOEt

• correct separation was obtained on TLC with the mobile phase cyclohexane–EtOAc (75:25). Again, the values obtained by the calculation were close to the experimental ones, with differentials of 7, 8 and 11% depending on the value taken for N (Table 2, entry 5). In each case, the calculation afforded values

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• (42%, 48% ee) yielded 26% of material with 95% ee. Assignment of absolute configurations (Scheme 3): Well grown crystals of enantiopure Michael product 30 suitable for X-ray structural analysis could be obtained by a second recrystallization from CH2Cl2/cyclohexane. The 4-bromophenyl residue allowed

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• °C and concentrated under reduced pressure. The residue was directly chromatographed over silica gel eluting with cyclohexane/AcOEt 4:1 followed by neat AcOEt to provide GemSQ-d6 (3) as a colorless oil (36.0 mg, 72%). 1H NMR (CDCl3, 400 MHz) δ 9.15 (br s, 1H, NHCO), 8.10 (d, J = 7.5 Hz, 1H, H-6

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• chromatography on silica gel (cyclohexane/ethyl acetate 4:1) yielded the desired product (1.61 g, 3.77 mmol, 96%) as a colorless solid. Rf 0.29 (cyclohexane/ethyl acetate 4:1); mp 84 °C; [α]20D −2.3 (c 0.5, CHCl3); 1H NMR (300.13 MHz, CDCl3) δ 0.09 (s, 6H), 0.93 (s, 9H), 1.24 (s, 3H), 2.43 (d, J = 8.0 Hz, 2H

• yellow to red. The solvent was removed under reduced pressure and purification of the residue by column chromatography on silica gel (cyclohexane/ethyl acetate 4:1) yielded the desired products 42 and 43 (766 mg, 1.75 mmol, 94%, dr 1:1.5 anti/syn) as off-white solids. 42: mp 129 °C; [α]20D −20.3 (c 0.5

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• Bamford–Stevens-like transformation, the reaction with the adjacent alkyne proved to be much faster to provide the bridged-polycyclic product 89. The conditions employed were sufficiently mild and chemoselective that the epoxide in cyclohexane 91 remained intact in the reaction to form 92. The use of

Separation and identification of indene–C₇₀ bisadduct isomers

• Bolong Zhang,
• Jegadesan Subbiah,
• David J. Jones and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2016, 12, 903–911, doi:10.3762/bjoc.12.88

• mixture of IC70BA was achieved by heating C70 with indene at 180 °C in 1,2-dichlorobenzene [9]. Following the reaction, flash chromatography (silica gel, toluene: cyclohexane, 1:9) was performed to remove any excess reagents, mono-adducts of C70 as well as other impurities. In our previous work, the

• contained the biggest portions of the original mixture, enough for device testing. Notably, fraction 9 contained two IC70BA species and was further separated by flash chromatography (silica gel, toluene/cyclohexane 1:9) into fraction 9-1 and fraction 9-2 which are known to contain the 2 o’clock-B isomer [9

• analyzed with a silica gel HPLC column (cyclohexane 1.0 mL/min), respectively, to assess their relative polarity. The HPLC chromatogram clearly illustrated that the retention time of fraction 10 was shorter than of fraction 11, which suggested that the configuration of fraction 10 was less polar than

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• reagents, also used as solvent, were cyclopentane, cyclohexane and cycloheptane. Two factors are noteworthy in this work. Unlike the carboxamide complexes (R)-18 and (S)-18 previously reported by Doyle and coworkers (Table 2), where the complexation of the chiral ligand to rhodium atoms occurs through the

• attributed to high steric demand required by the chiral ligand in the transition state of the carbenoid insertion step in the C(sp3)–H bond. Cyclic alkanes were also tested with yields ranging from 64–80% and enantioselectivities between 88 and 92% ee. The reaction with cyclohexane was conducted on a gram

Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

• Maria C. Guimarães,
• Mariene H. Duarte,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2016, 12, 760–768, doi:10.3762/bjoc.12.76

• possible for isoflurane. However, geometry optimization at the MP2/6-311++g(d,p) and ωB97X-D/6-311++g(d,p) (a DTF method which includes dispersion effects) levels converged to five energy minima for the gas phase, implicit solvents (cyclohexane, DMSO and water, using the polarizable continuum model), and

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

• initially formed aminoborylated product 3 were not successful, its formation was confirmed by 11B NMR (δ = 40.7 ppm in cyclohexane-d12). The crude reaction mixture was treated with pinacol and the yield of the product was estimated by 1H NMR spectroscopy. Using dtbpy, the common ligand for iridium-catalyzed

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• Bonne, Constantieux, Rodriguez and co-workers reported an enantioselective three-component Michael–Michael–Henry reaction to access a highly substituted cyclohexane 76 with excellent selectivity over three steps (>95:5 dr, 98% ee) using Takemoto’s catalyst 77 (Scheme 27) [46]. The cascade starts with a

• 2010, Zhao and his group demonstrated the synthesis of bicyclo[3.2.1]octan-8-ones 80, via a domino Michael–Henry reaction using quinine-derived catalyst 57 (Scheme 28) [47]. The nucleophile in this process is cyclohexane-1,2-dione (81) and the Michael acceptor is nitroolefin 82. A wide range of

• , Xu and co-workers described a three-compound reaction between dialkyl malonate 222, nitro-alkene 82 and substituted enal 154, catalyzed by the chiral quinine-derived thiourea 57 and organocatalyst 223, affording product 224 with a substituted cyclohexane-ring core (Scheme 70) [89]. The experimental

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• -methylallyl)benzamide (4a) and cyclohexane (2a) as model compounds (Table 1). As shown in Table 1, we found that the reactions did not happen or gave only a trace amount of the desired product with K2S2O8, AIBN, BPO and TBHP as oxidants (Table 1, entries 1, 3–5). PhI(OAc)2 and DCP could be used as oxidants

• examined, and a lower chemical yield was found when the reaction was performed at 100 °C (Table 1, entry 16). With the optimized conditions developed, we then carried out a substrate generality study using various types of N-(2-methylallyl)benzamides 4 to react with cyclohexane (2a). As shown in Scheme 2

• final study of this reaction was the investigation of the mechanism. Firstly, a substrate (8a) bearing a hydrogen atom at the nitrogen was tried for the current system. The cyclohexane radical addition product 9aa’, instead of a cyclization product, was observed with 35% yield (Scheme 5a). This result

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

• Cs2CO3 (20 equiv) were added. The reaction mixture was stirred under an atmosphere of argon for 12 h at 25 °C. Insoluble components were removed by filtration over celite. Column chromatography (silica gel) using cyclohexane/ethylacetate = 10/1 (v/v) yielded the corresponding complexes. The synthesis of

• ; HCl relative to ruthenium) was added to activate the reaction. The reaction was followed by TLC (cyclohexane/ethyl acetate = 3:1) and after complete conversion stopped with an excess of ethyl vinyl ether. The Polymer was precipitated in vigorously stirred methanol (approx. 25 mL for 100 mg polymer

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds. Keywords: cyclohexane carbonylation; fluorine containing building blocks: organofluorine chemistry; Introduction Selectively fluorinated building blocks

• cyclohexane rings, to complement aromatic building blocks. In this context we have recently prepared the all-cis-tetrafluorocyclohexanes 2 and 3 [3][4] and also all-cis-hexafluorocyclohexane (1) [5] as shown in Figure 1. In the case of the hexafluorocyclohexane, the ring maintains a chair conformation and

• demonstrated that 4 can be elaborated in a relatively straightforward manner by mainstream reactions of electrophilic aromatic substitution [7]. This extended to the synthesis of cyclohexane substituted (S)-L-phenylalanines with orthogonal protecting groups suitable for their incorporation into peptides [8

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• cascade reaction, investigating novel trans-1,2-cyclohexane diamine-based bifunctional ammonium salts 8. These catalysts were recently introduced by our groups in a variety of different reactions [27][28][29], as exemplified by a related aldol-initiated cascade reaction of glycine Schiff base with 2

• isoindolinones. This work: 1) trans-1,2-cyclohexane diamine-based bifunctional ammonium salts 8 in the asymmetric synthesis of 7; 2) transformation of 7 into 9; 3) asymmetric synthesis of bioactive isoindolinones. Asymmetric cascade, crystallization and decarboxylation reaction. Proposed racemization pathways of

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• from allyl phosphate 2d. Various alkenes were examined using the allyl chloride 2a system (Scheme 2). The reaction showed tolerance in functional groups such as CF3 (6, 75% ee) Cl (7, 77% ee), and cyclohexane (8, 88% ee). Electron rich allyl silane could also be used to introduce a TMS group (9, 93% ee

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• , the reaction of 5a (0.2 g, 0.415 mmol) was performed at different concentrations (2.5, 5, 10, and 15 equiv) of cyclohexane carbonitrile (Table 1, entry 3) in dry toluene using TMSOTf (1 equiv) at 0 °C to rt under N2 atmosphere. A complex mixture of products was obtained with 2.5 equiv and 5 equiv of

• nitrile, along with trace amounts of product. Using 10 equiv of cyclohexane carbonitrile gave moderate yield of product 8a along with the formation of di-D-fructose dianhydride or spiroketals [49] as the side product. Finally, 15 equiv of nitrile served best for this transformation providing

• the β-orientation, leading to a high stereoselectivity. Finally, due to the widespread applicability of chiral oxazolines, the synthesis of fructose-derived spirooxazolines was examined on a multigram scale. For example, the reaction of 5a (1.2 g, 2.49 mmol) with cyclohexane carbonitrile (15 equiv) in

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

• has been performed varying the catalyst to substrate ratio, but maintaining the concentration of the catalyst as a constant. Thus, 100:0, 80:20 and 60:40 v/v mixtures of styrene and cyclohexane, respectively, have been reacted with EDA (0.285 mmol) with the same catalyst precursor (see Experimental

• ). Under these conditions, cyclohexane is much less reactive than styrene and acts as an inert solvent [29]. The kinetic curves for these three experiments are shown in Figure 2. The plot of kobs vs substrate concentration evidences a direct correlation between styrene concentration and kobs. The same

•  2 is observed with cyclohexane or dichloromethane as dilution agents must be interpreted as the result of their independent behavior in the process, not being involved in any effect relative to polarity or solubility issues. Mechanistic interpretation It has been reported by several authors that the

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• bond was not favored. More notably, the exploration on the reaction mechanism disclosed that the activation of the alkyl C–H bond was initiated by the tert-butoxy radical (Scheme 6). Inspired by the alkane C–H activation, Yu and Cheng et al. [51] discovered that directly heating amides in cyclohexane

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• manifested in the batochromic (Δλ = 15–19 nm) shift of the longest wavelength absorption band as compared with the parent 2-(2-hydroxyphenyl)benzoxazole (cyclohexane, λmax = 321, 334 nm [35]). The excitation spectra of ASS-luminescence correspond to the absorption spectra of the hydroxy form of compounds 11a