The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• Finnigan LTQ FT Ultra Fourier Transform Ion Cyclotron Resonance device at 250 °C for ESI. IR spectra were recorded on a Perkin Elmer FT-IR Paragon 1000 instrument as neat materials. Absorption bands were reported in wave numbers (cm−1), obtained on a ATR PRO450-S accessory (Jasco). Melting points were

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• conditions. Again a small amount of catalyst (S,R)-C2 (2.5 mol %) gave the best chemical yield, 70% using solvent-free, neat stirring at 30 °C. In comparison, the ball-mill reaction afforded 66% of the product (Table 4, entries 5–7). The Michael addition of aldehyde 6c gave under dry stirring products 8e and

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• 15a was heated in capped tubes under microwave conditions [35][36][37] for 10 minutes in solvents such as ethanol (100 °C), xylene (150 °C) or N,N-dimethylformamide (150 °C) (Table 1, entries 3–5). Dissolution in neat protic or Lewis acids (e.g., hydrochloric acid, trifluoroacetic acid

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in MeCN, the yield could be improved to 32% (Table 1, entry 4). Further screening of other oxidants revealed that NMO was the optimal (Table 1, entries 9–11). When the reaction was conducted in neat in the presence of 2-pyridone, 3a was obtained in 36% yield (Table 1, entry 12). However, significant

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• . disclosed the quaternary ammonium N-F reagent, N-fluoroquinuclidinium fluoride (6-1) [43]. They subsequently followed with more detailed results in 1988 [44]. Quinuclidine was fluorinated by neat fluorine in trichlorofluoromethane at −72 °C, affording the product 6-1 in 86% yield (Scheme 15). Fluorination

• reactivity than the sulfonamide reagents such as Barnette’s N-fluoro-N-alkylarenesulfonamides, since the electronic density on the nitrogen was greatly decreased by two strong electron-withdrawing CF3SO2 groups. Reagent 7-1a reacted slowly with benzene and toluene under neat conditions, whereas activated

• pentafluoropyridine, the precursor 11-1 was prepared as illustrated in Scheme 25. Treatment of 11-1 with neat F2 in acetonitrile at −10 °C under reduced pressure gave N-fluoro-sulfonamide 11-2 in 89% yield. This product was however a 9:1 mixture of the N-F reagent 11-2 and the protonated compound of 11-1. The

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• , HMQC, and HMBC). The UV–vis spectra were measured on a PerkinElmer Lambda 45 spectrophotometer in spectroscopic grade CH2Cl2. MS (ESI) were performed with a Varian 500-MS LC Ion Trap. The IR spectra were measured neat with an Agilent Cary 630 FTIR spectrometer. Elemental analyses were obtained with a

• , 133.4 (2i-C), 134.2, 135.0 (CH each), 138.1, 139.0 (2i-C), 140.8 (q, 2JC,F = 40.8 Hz, C(3)), 174.5, 177.3 (2C=O); 19F NMR (CDCl3, 565 MHz) δ −62.82 ppm; UV–vis (CH2Cl2) λmax (log ε) 247 (4.45), 266 (4.24), 275 (4.25), 340 (3.72), 409 (2.61), 496 nm (1.70); IR (neat) νmax: 3082, 1677 (C=O), 1588, 1521

• ) δ 13.6, 13.9, 14.2, 14.6, 20.8 (5Me), 64.8, 80.1 (2i-C), 120.7 (q,1JC,F = 271.1 Hz, CF3), 120.7, 129.6 (2CH each), 134.8 (i-C), 140.0 (q, 2JC,F = 36.3 Hz, C(3)), 139.5, 146.9, 147.1 (3i-C), 192.6, 195.1 (2C=O) ppm; 19F NMR (CDCl3, 565 MHz) δ −61.45 ppm; IR (neat) νmax: 2930, 1677 (C=O), 1513, 1506

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• screening of several reaction conditions, we found that heating at 120 °C of a neat mixture consisting of 1-methyl-1H-indole-2-carbaldehyde (1a, 2.0 equiv), glycine methyl ester HCl salt (2a, 1.0 equiv), and DIPEA (3.5 equiv) in a sealed tube for 6 h, led to the isolation of γ-carboline 3aa in 70% yield

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

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• production of biodiesel [5][80], intermediates for triazine synthesis [48], etc. Some derivatives were grafted onto polystyrene resins for catalytic uses [5]. Various solvents and temperatures were used such as hot DMF [5], neat [79], toluene or hexane at 25–100 °C [79]. Generally, higher temperatures seem

• curing processes. [79]. For example, Sakai et al. initially used quite harsh conditions for the reactions with dialkylcarbodiimides (neat, 100 °C, 2 h) that led to relatively low yields. Later, they applied smoother room temperature conditions for arylalkylcarbodiimides and diaryl derivatives: either

• neat for 30 min, or 24 h diluted in an apolar solvent. Both of these conditions proved very efficient even for hindered reagents and displayed good to excellent yields (Scheme 39B). In the search for new biguanide-based organocatalysts for the transesterification of vegetable oils, Glasovac et al

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -assisted four-component reaction involving chromene-aldehyde (61), amines 32, acyclic 1,3-diketones 54 and nitromethane using silica-gel-supported polyphoshoric acid as catalyst under neat conditions for the synthesis of tetra-substituted pyrroles 62. A comparative study of the protocol employing the

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• ); (b) AcCl, HCl, Et2O, rt, 24 h, 70%; (c) KHF2, neat, 105–110 °C, 60%. Attempted synthesis of 4. Reagents and conditions: (a) Ca(OH)2, 1,4-dioxane/water, reflux, 72 h, 5% (by HPLC integration); (b) ClF2CO2Na, K2CO3, DMF, 95 °C, 4 h, 7 (4%), 8 (19%). Synthesis of 10. Reagents and conditions: (a

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• ATR diamond crystal (neat solid samples). Flash chromatography was performed using a Büchi Reveleris® X2 flash chromatography system equipped with a UV–vis/ELSD detector and Reveleris Flash pure cartridges (12–40 g, 35–45 μm, 53–80 Å) or puriFlash® Alumine N 32/63 µm cartridges (12 g). General

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• , 129.5, 129.6, 130.0, 130.7, 131.2, 131.6, 133.8, 134.0, 140.2, 140.9, 141.4; IR (neat) ν: 3055, 3020, 2976, 2883, 1471, 1442, 1433, 1398, 1194, 1130, 1038, 1009, 943, 872, 837, 822, 752, 706, 621, 573, 538 cm−1; HRMS (EI) m/z: [M]+ calcd. for C26H26O4, 402.1826; found, 402.1815. Gram-scale synthesis

• , 124.8, 125.2, 126.8, 129.0, 129.05, 129.13, 129.9, 131.0, 133.8, 134.5, 138.8, 142.6; IR (neat) ν: 3053, 2966, 2883, 1489, 1396, 1132, 1043, 984, 831, 756 cm–1; HRMS (APCI+) m/z: [M + H]+ calcd. for C30H29O4, 453.2060; found, 453.2081. Gram-scale synthesis: Compound 4b was also prepared by the method

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• toluene, MeCN, and DCM, and in the presence of 1–20 equiv of P(OEt)3, the formation of the desired phosphonates 4 was not observed (Scheme 6). We started an optimization of the reaction conditions using substrate 6d, and reactions in neat phosphite at various temperatures were tried (Table 2). The

• hours in neat P(OEt)3 at 160 °C. With the experimental conditions in hand, the SNAr–Arbuzov reaction between 2,6-bistriazolylpurines 6a–i and P(OEt)3 provided a library of novel purine phosphonates 4a–i in 27–82% yield (Table 3). The products 4a, 4d, 4e, and 4i were easily precipitated from hexane left

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• (Table 3, entry 5). To decrease reaction times further, we carried out the reaction in neat TFA/TES mixture (4:1 v/v, 5 volumes) and obtained a 62% conversion at just rt after 24 h (Table 3, entry 6). The product distribution was even further improved by addition of water to the reaction mixture to avoid

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• azaarene derivatives under neat conditions through a highly atom-economical pathway. To evaluate the preparative potential of this process, gram-scale reactions were performed up to a 10 g scale. Keywords: aldehydes; azaarenes; benzylic addition; green chemistry; solvent-free conditions; Introduction

• perspective, we herein disclose environmentally benign, atom-economical, catalyst-free nucleophilic additions of benzylic-like azaarene C–H groups to various benzaldehydes under neat conditions (Scheme 3). Results and Discussion With the purpose to develop an environmentally benign process, we first examined

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• . Experimental General procedure: An oven-dried narrow-mouth FEP tube (Nalgene®, 10.0 mL) containing a magnetic stirring bar was charged with substrate 1 (0.3 mmol), FLUOLEAD® (225.3 mg, 0.9 mmol, 3.0 equiv) and the nHF·pyridine complex (HF 70%, pyridine 30%, 1.5 mmol, 5.0 equiv, neat). The tube was tightly

• by FLUOLEAD®. The substrate scope of acyl fluorides. Reaction conditions: 1 (0.3 mmol), FLUOLEAD® (0.9 mmol, 3.0 equiv) and nHF·pyridine (1.5 mmol, 5.0 equiv) in neat conditions at 70 °C for 24 h. Yields in parentheses were determined by 19F NMR spectroscopy. aAt 100 °C. bUsing 1a (1.0 g, 5.0 mmol

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• dichloromethane, acetonitrile, and acetone (Table 1, entries 1–3), whereas 4-chlorobiphenyl (2a) was observed in traces as the only product in neat methanol (30% of 1a consumption, Table 1, entry 4). Interestingly, the addition of water (a methanol/water 2:1 mixture) increased the overall yield of the product 2a

• was observed with compound 3c, where a single emission band located at ca. 290 nm is observable in neat methanol, whereas the presence of TFE causes a lowering of that emission, in favor of a second band in the 330–350 nm region (Figure 4). These two emissions have been assigned, on the basis of our

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• the mannose analogue 14 in higher yield and using pyridine·1HF as reagent (pyridine·9HF with 120 equivalents of pyridine) allowed only poor conversion of starting material. Finally, performing the reaction in neat Et3N·3HF (no additive) provided almost exclusively talose analogue 12 with no

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• reaction for the synthesis of substituted dihydropyridines was performed under green heterogeneous and neat conditions in the presence of 0.04 g/mmol of a 40 wt % phosphotungstic acid on alumina catalyst, which is simple, safe and environmentally benign to prepare, fully recoverable, and reusable for up to

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• -temperature operation. The sample temperature was calibrated against neat ethylene glycol and neat methanol standards. Selective inversion experiments at subambient temperature effected the selective inversion with iBURP shapes [25]. The spin–lattice relaxation time T1 for each site was determined with

Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination

• Maëva-Charlotte Kervarec,
• Thomas Braun,
• Mike Ahrens and
• Erhard Kemnitz

Beilstein J. Org. Chem. 2020, 16, 2623–2635, doi:10.3762/bjoc.16.213

• presence of HSiEt3, either in a solvent (C6D6 or C6D12), or in neat silane under similar conditions (all reactions were carried out at 70 °C and monitored for 7 days). The treatment of 10a and HSiEt3 in C6D12 generated 1 and 10b again, in addition to traces of 1,1,2-trifluoropropene (2, Scheme 4, top). The

• , middle). Compound 10a is transformed into 1, 11, and 12 with the additional presence of traces of the Friedel–Crafts product CF2=CFCH2C6D5 (3). However, in neat silane, 10a was converted into 1, 10b, 2, 1,1,1,2-tetrafluoropropane (13), 1,1-difluoropropene (5), and 1,1,1-trifluoropropane (6, Scheme 4

• reaction patterns and to demonstrate the conceivable transformations between certain products, which were observed in the activation of 10a in the presence of ACF and HSiEt3. It turned out that the tetrafluoropropene 13 reacts in the presence of silane with ACF as the catalyst in C6D12 or neat silane to

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• . Conclusion In summary, the overall molecular polarity is influenced not only by the nature of the substituent group (as considered by additive techniques of prediction), but also by the orientation of the neat molecular dipole moment vector. In this sense, methods that ignore such influences result in

Host–guest interaction of cucurbit[8]uril with oroxin A and its effect on the properties of oroxin A

• Zhishu Zeng,
• Jun Xie,
• Guangyan Luo,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 2332–2337, doi:10.3762/bjoc.16.194

• containing 10% DMSO by volume, OA (500 μmol·L−1) upon the addition of different molar equivalents of Q[8]: (a) 0, ( b ) 0.35, (c) 0.44, (d) 1.03, (e) 1.60 and (f) neat Q[8]. (A) The UV–vis absorption spectra recorded for OA in the presence of Q[8] (c(Q[8]), labeled a–k: 0, 0.2, 0.4, 0.6, ..., 2.0 × 10–5