Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• Merck. For 1H and 13C NMR analysis a Bruker Avance I 400 MHz instrument was used with 400 MHz for 1H spectra, 162 MHz for 31P spectra and 101 MHz for 13C spectra or a Bruker Avance I 500 MHz instrument was used with 500 MHz for 1H spectra and with 126 MHz for 13C spectra. The allocation of NMR signals

1,8-Bis(dimethylamino)naphthyl-2-ketimines: Inside vs outside protonation

• A. S. Antonov,
• A. F. Pozharskii,
• P. M. Tolstoy,
• A. Filarowski and
• O. V. Khoroshilova

Beilstein J. Org. Chem. 2018, 14, 2940–2948, doi:10.3762/bjoc.14.273

• . Structural investigations The structural investigations started with a 1H NMR analysis of the imines 4a–7a in acetone-d6, CD3CN and DMSO-d6 in a wide range of temperatures. The main attention was paid to the chemical shift and the shape of the C=NH and NMe2 groups’ signals. Upon temperature decrease, the NH

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• over-reduction since 1H NMR analysis of this trial pointed out the coexistence of unreacted material 6ae along with (traces) of the over-reduced compounds 11 and 12. We applied this finding to the reduction of 6ag and had to allow for the low solubility of this compound in ethanol and thus run the

• to sodium carbonate (note e in Table 2). Unfortunately, if the 1H NMR analysis of another chromatographic fraction obtained when purifying these trials pointed out the occurrence of inseparable mixture of aliphatic compounds, these could never be properly purified and identified. A mechanistic

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• considering the phenyl derivative of 6a, a sobering 35% isolated yield was obtained, in stark contrast to the reported 95% yield published in 1980 [7]. In our hands, 1H NMR analysis of the crude condensation product pointed out the occurrence of the intermediate acrylate 2a along with a large amount of methyl

• benzoate, a well-known side product in this reaction [7][8]. From the aryl acetals 5g–l featuring electron-withdrawing groups, low to non-detectable amounts of the condensations products 2g–l were observed by 1H NMR analysis, and this was reflected in the isolated yield of the corresponding α-nitroesters

• NMR analysis of the crude reaction mixture. Indeed, a slow ring-opening reaction took place upon standing in solution to mainly give the isoxazole isomer 28 along with much less of the target oxazole-bearing α-hydroximino ester 29. Extensive trials to alter the selectivity of the ring opening using

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• equivalent nitroalkene, 1.2 equivalents of salicylaldehyde and 0.1 equivalents of DABCO as catalyst in the first step at 40 °C, and 2 equivalents of benzyl azide, 2 equivalents of acetic acid, 0.3 equivalents of BHT as antioxidant, 4 Å MS and DMF under argon atmosphere at 120 °C in the second step. Crude NMR

• analysis of the reaction mixture under optimized conditions showed solely regioisomer 5a, which was obtained in 54% yield after chromatographic purification. Additionally, the optimized conditions gave improved yields compared to the two-step synthesis and circumvented the formation of oxidized side

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• stereoisomers of 3,4,5-tris(2-methoxyphenyl)-2,6-dimethylpyridines determined by X-ray analysis [38]. Graphical representation of kinetic, time-dependent 1H NMR analysis of (syn)-7 (100 °C). Graphical representation of kinetic, time-dependent 1H NMR analysis of (syn)-10 (120 °C). HT-NMR (300 MHz, DMSO-d6

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• 1.5 years in the refrigerator [35]. In order to examine the stability of 2-Zn in more detail, we quantitatively evaluated the thermal stability of 2-Zn under various temperature conditions (Figure 2). After a given duration, the recovery yield of 2-Zn was determined by 19F NMR analysis using an

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

•  3) [32]. After derivatization and determination through Mosher’s ester analysis [33][34][35], the absolute configuration of the newly generated secondary hydroxy group-bearing carbon center (C6) was determined as R configuration (see Supporting Information File 1). The NMR analysis of the Mosher’s

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• catalyzed by DHNO is identical to that of the LHNO reaction, so that this enzyme was also initially identified as catalyzing the oxidation of the C2–C3 bond [17]. However, NMR analysis of the product has also recently established that DHNO catalyzes oxidation of the C2–N bond [24]. The sequence of DHNO from

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• spectrum of the mixture of 1 and 2+ in CDCl3 remained unchanged after 48 h at 298 K, thus showing that the system had reached the equilibrium condition. At this point, an apparent association constant of 6.2 ± 0.3 × 103 M–1 was calculated by quantitative 1H NMR analysis (tetrachloroethane as internal

• transferred into a NMR tube for 1D and 2D NMR spectra acquisition. Determination of apparent Kass value for pseudorotaxanes 2+1cone, 3+1cone and 3+11,2,3-alt, by quantitative 1H NMR analysis. The sample was prepared by dissolving calixarene 1 (3.0 × 10−3 M) and the ammonium TFPB salt 2+ or 3+ (3.0 × 10−3 M

• studies. Also in this case, after equilibration at 298 K for 24 h, this preference was reversed in favour of the 3+1cone atropoisomer, with a 3+1cone/3+11,2,3-alt ratio of 8/1. From the equilibrium mixture, an apparent association constant of 9.3 ± 0.4 × 102 M−1 was calculated by quantitative 1H NMR

Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3-triazoles

• James T. Fletcher,
• Matthew D. Hanson,
• Joseph A. Christensen and
• Eric M. Villa

Beilstein J. Org. Chem. 2018, 14, 2098–2105, doi:10.3762/bjoc.14.184

• measurement of each triazole-containing species as a relative molar fraction within the dynamic reaction mixtures was made using 1H NMR analysis. This was accomplished by integration of the distinguishable triazole signals for each iminotriazole and formyltriazole analog contained in this study. Signal

Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• were exclusively obtained (mixture of positional and geometric isomers) in 97% yield. It was shown by 1H NMR analysis that the mixture contained about 60% of 2-octadecene (E/Z mixture). Having established the reaction conditions, we then screened the scope and limitation of substituted acetophenone

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• THF solutions at 60 °C by starting with equimolar amounts of substrates. After 2 h, completion of the reaction was confirmed by TLC, and, after typical workup, products 4 were obtained as colored solids in high yields (Scheme 1). The 1H NMR analysis revealed that the initially formed [4 + 2

• cycloadducts could be expected, but the 1H NMR analysis of the crude products showed that only one product was present in each case and, therefore, the studied [4 + 2] cycloaddition reactions occurred with complete regioselectivity. Based on the assumption that the nucleophilic S-atom of the thiochalcone

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• switched to a stronger oxidant, Pb(OAc)4. To our pleasure, hydrazone 11 was successfully oxidized to provide the required azoester 12. However, NMR analysis revealed that compound 12 was impure and contained also some cyclized byproduct [47]. Furthermore, it was discovered that compound 12 was quite

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• -isopropyl-5-methylcyclohexanol ((−)-menthol, 1i). The reaction afforded an almost 1:1 mixture of only two diastereoisomers as determined by 1H and 13C NMR analysis of the crude reaction mixture, thus suggesting that it occurs with no epimerization at C1. This result was confirmed by submitting compound 3i

• to acid-catalyzed deprotection with H2SO4@SiO2 (25 wt % [33] as depicted in Scheme 3). Alcohol 1i, was recovered as a single stereoisomer, identical to the commercially available starting material, as determined by 1H and 13C NMR analysis of the crude reaction mixture (see Supporting Information File

Direct electrochemical generation of organic carbonates by dehydrogenative coupling

• Tile Gieshoff,
• Vinh Trieu,
• Jan Heijl and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2018, 14, 1578–1582, doi:10.3762/bjoc.14.135

• sufficient conversion for further studies. By optimization studies, we were able to produce 21% of the organic carbonate according to 1H NMR analysis on a 0.5 mmol scale (Scheme 2). Similar to the conversion of xylene, we also detected a weak signal of the corresponding side-chain functionalized product

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• funding. We also thank Barbara Woods and Orla Fenelon for HRMS analysis, and Dr. Ken Maddock for his assistance with NMR analysis.

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• consistent with the Steven’s hypothesis. Keywords: cation pool; conformation; electroorganic synthesis; N-acyliminium ion; NMR analysis; piperidine; Introduction Cyclic amines are significant key motifs in pharmaceutical and natural products because a variety of compounds bearing those moieties exhibit

• between Hd and Hg. These results suggest that Hd adopts an axial and the phenyl group a pseudo-equatorial position at low temperature. The low temperature NMR analysis of C3, which has a phenyl group at 5-position, was next performed and the 1H NMR spectrum is depicted in Figure 2. An axial–axial coupling

• NMR analysis (Figure 3). The signal of Hf was observed as a triplet due to the axial–axial coupling with He and the geminal coupling with Hg, and these results indicate that the phenyl group of C5 is placed in the pseudo-axial position. The low temperature NMR measurements of N-acyliminium ions C2, C4

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• reaction of 2,3-benzotropone (12) with dimethyloxosulfonium methylide in yields of 35% and 28% and investigated the structural characterization of these compounds by extensive NMR analysis (Figure 7 and Scheme 34) [146]. In addition, carbonium ions 198–201, prepared via the protonation of 2,3-benzotropone

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• previous report [25], a proposed reaction pathway is depicted in Scheme 5. At the beginning of the reaction, PhI(OAc)2 predominantly exists rather than 4, as confirmed by NMR analysis. Therefore, in the initial stage, PhI(OAc)2 preferentially undergoes decomposition with I2 to provide acetyl hypoiodite

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• –Grubbs catalyst (II gen.) afforded the target macrocycle 25 in 26% yield (Scheme 4). The E-configuration of the newly created C=C-bond in the final product was proven by 1H NMR analysis (J15-15’ = 15.9 Hz). Conclusion In summary, we proposed an efficient method of the synthesis of a 31-membered

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• 1,2-diazine as well as 1,2,4,5-tetrazine. Its stability towards air and moisture was demonstrated by NMR analysis and enables its application in organic synthesis without using a glovebox. A new one-pot procedure for its synthesis was developed starting from 1,2-bis(trimethylsilyl)benzene, which will

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure (350 mmHg). The concentrated solution was used without purification for the next protection reaction. The yield of alcohol product 2 was determined by 19F NMR analysis using benzotrifluoride (BTF) as an internal standard

• determined by 19F NMR analysis. p-Nitrobenzoylated alcohol 2a’ was purified by silica-gel column chromatography (EtOAc/hexane 1:40) as a colorless liquid (53% yield for 2 steps, 89% ee). 1H NMR (300 MHz, CDCl3) δ 8.34–8.31 (m, 2H), 8.24–8.20 (m, 2H), 4.33 (q, 4H, J = 6.9 Hz), 1.97 (d, 3H, J = 0.9 Hz), 1.28

• isomer 23.8 min. (S)-1-Ethoxy-3,3-difluoro-2-methyl-1-oxopropan-2-yl benzoate (2g’) Reaction temperature was −78 °C. The yield of alcohol 2g (89%) was determined by 19F NMR analysis. In the protection of alcohol, benzoyl chloride was used instead of p-nitrobenzoyl chloride. Benzoylated alcohol 2g’ was

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• NMR analysis). As a further application of the iodine(III)-mediated oxidative cycloaddition reactions, the present method was extended to HDA reactions with masked o-benzoquinones (MOBs) generated by the oxidative dearomatization [26][27][28][29] of guaiacols with methanol (Scheme 2). Liao’s and other