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

• could envisage rotation about the C–C single bond in the zwitterionic mesomer of (E)-15a (i.e., 15a') leading to the rotamer 15a", and hence (Z)-15a. It must be noted, however, that we never managed to obtain direct evidence, whether by TLC or NMR spectroscopy, for the short-lived intermediate (Z)-15a

• and 4-nitro congeners in acetonitrile, followed by sulfide contraction of the resulting thioiminium ether salts with triethylamine and triethyl phosphite, afforded the (E)-enaminones 25a–c in yields of 86–89%. The E-geometry of 25a was again confirmed by NOESY NMR spectroscopy, which showed an

In-depth characterization of self-healing polymers based on π–π interactions

• Josefine Meurer,
• Julian Hniopek,
• Johannes Ahner,
• Michael Schmitt,
• Jürgen Popp,
• Stefan Zechel,
• Kalina Peneva and
• Martin D. Hager

Beilstein J. Org. Chem. 2021, 17, 2496–2504, doi:10.3762/bjoc.17.166

• depicted in Supporting Information File 1. Furthermore, the polymers were analyzed using NMR spectroscopy. Herein, all signals could be assigned to both moieties within the polymers, the perylene and the polymer backbone. All spectra are shown in Supporting Information File 1. Characterization of the

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• phenylacetylene (Alk-3) in the presence of copper(II) chloride/ N,N,N’,N’,N’’-pentamethyldiethylenetriamine (CuIICl2/PMDETA) and exfoliated BPNs under the white LED irradiation was performed (Figure 3). The reaction was followed by 1H NMR spectroscopy during the click process. The decrease of the acetylene proton

• the photoinduced CuAAC reactions. UV–vis spectra of CuICl, CuIICl2 and BPNs. a) 1H NMR spectra of the model reaction between benzyl azide (Az-1) and phenylacetylene (Alk-3) before (black) and after (red) irradiation. b) Conversion-time plot as measured by 1H NMR spectroscopy through integration of the

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• needed for acceptance of GGPP. To determine the absolute configurations of 8 and 9, large scale enzyme reactions with GGPP were performed. Compound 8 was isolated from the A222V variant and 9 from the A222M variant and their structures were ultimately confirmed by NMR spectroscopy (Supporting Information

• to incorporation of deuterium into diastereotopic hydrogen positions that can be distinguished by NMR spectroscopy. Herein, the additional 13C-labellings allow for a sensitive analysis by HSQC spectroscopy (Figure 7). Conversion of both substrates (R)- and (S)-(1-13C,1-2H)GGPP with the SmTS1 A222M

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

• ], it was shown by means of NMR spectroscopy and DFT calculation that the protonation of these oxadiazoles in Brønsted superacids TfOH and FSO3H gave reactive N,C-diprotonated species. The protonation of oxadiazoles 1 takes place at the nitrogen N4 and the α-carbon of the side chain C=C bond. One would

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• chromatography separation is not usually required. This outcome indicated that the transformation could be applicable for larger-scale syntheses of 3-monohalooxindoles products. In addition, the structure of all products 3 and 4 was unambiguously assigned by 1H and 13C NMR spectroscopy and HRMS. Especially the

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• via NMR spectroscopy or UV–vis measurement was possible due to the extremely high molecular weights of the particles. The NMR spectra in D2O showed only very broad peaks of low intensity and no aromatic peaks, indicative of TPP attachment, were detected. This could of course mean that TPP has either

• same conditions as described above. The conjugation product was analysed using 1H and 31P NMR spectroscopy. The 31P NMR spectrum (Figure 2a) shows a peak at 23.07 ppm which belongs to the phosphorus of the triphenylphosphonium moiety. Furthermore, the additional peaks in the region between 7.5–8.2 ppm

• 8.2 and the reaction was left to stir at room temperature for 3 days. The polymer was purified by dialysis in Milli-Q water with frequent solvent change (regenerated cellulose membranes, MW cut-off 6000–8000 g mol−1) and the product was then lyophilized and analysed using NMR spectroscopy. 1H NMR (300

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• NMR spectroscopy. All these polymers 61–65 were soluble in common organic solvents like THF, dichloromethane, and chloroform and had Mn in the range 6000 to 21000 Da with PDI of 1.3–1.6. The polymers 61–65 displayed stimuli-responsive behavior as evidenced by shifting of their absorption bands from

• -diboronate 103 with varying ratios of 1,3-dibromoazulene (4) and 4,7-dibromoazulene (12) under Suzuki reaction conditions (Scheme 20). As stated above in the case of azulene-thiophene polymers 61–65, the final composition of 1,3- and 4,7-regioisomers of azulene in the polymer chain was determined by 1H NMR

• spectroscopy. All these polymers were soluble in common organic solvents like THF, dichloromethane, and chloroform, and had Mn in the range 9800 to 34300 Da with PDI of 1.6–2.2. The absorption studies conducted on these polymers revealed their stimuli-responsive nature in protonated states and the influence of

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• Michael acceptor to alcohol was set to 1 to 2 and no additional solvent was used. The reaction was carried out at room temperature with 1 mol % catalyst (with respect to the Michael acceptor). The reaction progress was monitored after 1 h and 24 h using 1H NMR spectroscopy. The set-up of the study aims to

• %, because 1 mol % was not sufficient to obtain satisfying conversions. The reaction mixture consisting of 4 and the catalyst was either stirred at room temperature or put in a drying chamber operated at 80 °C. Aliquots of the reaction mixture were sampled after 1 and 24 h and analyzed by 1H NMR spectroscopy

• conditions. Four different conditions were chosen. Undissolved solid samples and samples dissolved in chloroform or in 1-hexanol were kept at room temperature and solutions in 1-hexanol were also heated at 80 °C. The reaction mixture was then investigated via 31P NMR spectroscopy. Under all conditions, the

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -triazole intermediate 107, followed by intramolecular 1,6-conjugate addition to afford the final product. To find the exact mechanism, the reaction was performed in CDCl3 as solvent in an NMR tube with a catalytic amount of AgSbF6 and then, the reaction mixture was analyzed using 1H NMR spectroscopy. The

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• determined by 1H NMR spectroscopy. Chromatographic separation was carried out on silica gel 60H (200–300 mesh) manufactured by Qingdao Haiyang Chemical Group Co. (China). High-resolution mass spectrometry (HRMS) was measured on a Thermo-DFS mass spectrometer. NMR spectra were recorded on a JEOL 600 NMR

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• . Moreover, the photoconversion yield for the E→Z isomerization is quantitative (within the detection limit of UV and NMR spectroscopy). A high efficiency in switching the biological activity off is important to avoid side effects of residual concentrations of the active form [13]. Water solubility and high

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• product 5 and unwanted side product 11 (Scheme 3) which were not distinguishable by 1H NMR spectroscopy. Carrying side product 11 through the subsequent synthetic steps resulted in compounds 12 and 13 and ultimately product 9 (Scheme 2), the first point in the sequence where the isomeric products were

• separable and clearly distinguishable by 1H NMR spectroscopy. The formation of 11 was not apparent when using an acetonide protection strategy (Scheme 1) because the desired product 14 was easily separated by column chromatography from the undesired compound 15, emanating from diol 11 (Scheme 3). However

• addition of the chiral auxiliary. Our attention then turned to the stereoselective reduction of 8. Chelation-controlled reduction of 8 using ZnCl2 and DIBALH allowed for the successful formation of 16 as a single diastereomer (Scheme 4), as evidenced by 1H NMR spectroscopy [18]. TBS deprotection furnished

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• Technology Prague, Technická 5, 16628 Praha 6, Czech Republic NMR Spectroscopy group, Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 542/2, 16000 Praha, Czech Republic 10.3762/bjoc.17.85 Abstract Multiple fluorination of glycostructures has emerged as an attractive way of

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• chemical properties, there was no difference between the products of the two reactions. Since the relative configuration of compound 9 was clarified by NMR spectroscopy and X-ray crystallographic results, we were able to assign the stereochemistry of spiro-derivate 12, too. In a similar manner, the LiAlH4

• of the five components 15A–E were determined by 2D NMR spectroscopic techniques (NOESY and HMBC). Since this finding is quite unusual in the case of Schiff’ bases, we decided to study the ring/chain tautomeric mixture (15A–E) in the reaction of 13 with benzaldehyde by 1H NMR spectroscopy. When a time

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• 1H NMR spectroscopy, which indicated the presence of two doublets at δH 7.88 (d, J = 9 Hz, 1H) and δH 7.19 (d, J = 8.9 Hz, 1H), corresponding to the two adjacent hydrogen atoms of the phenolic ring. One singlet was observed at δH 10.58, evidencing the aldehyde proton. This access to previously

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• during the glycosylation with glycosyl fluorides in liquid SO2 is proved by 19F NMR spectroscopy. A sulfur dioxide-assisted glycosylation mechanism that proceeds via solvent separated ion pairs is proposed, whereas the observed α,β-selectivity is substrate-controlled and depends on the thermodynamic

• alcohol yielding silyl ether [65][66] that do not react further with glycosyl fluoride α-1a under our conditions. The formation of silyl ether was detected in a crude reaction mixture by NMR spectroscopy. When the optimized model reaction (Table 1, entry 2) between mannosyl fluoride α-1a and 2

• -phenylethanol (2a) was carried out in pure conventional solvents (MeCN, THF, toluene or DCM) often used for glycosylation, no reaction was observed (Table 2, entries 1, 4, 6 and 9). Only traces of mannoside 3a and/or hemiacetal α-4 were detected by NMR spectroscopy in the presence of H3PO4 as a protic acid

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• identification of mismatches and the binding of RNA-processing proteins with chemical shift dispersions as large as 4 ppm, suggesting that this modification has a wide use for the determination of a variety of RNA structures through NMR spectroscopy [211]. In contrast, the incorporation of 4'-C-aminoalkyl-2'-O

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• mixture of Ph2P(O)PPh2 (1, 0.6 mmol) and 1-octyne (2a, 0.4 mmol) was irradiated with a xenon lamp. After 40 hours, sulfurization of the addition product was performed to afford the phosphinylphosphination product 3a in 45% yield, confirmed by 31P NMR spectroscopy (Scheme 2) [47]. Next, the reaction was

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• structures of the compounds were elucidated through 1D and 2D NMR spectroscopy. It was determined that trigonoine A was a β-carboline alkaloid containing a 2,8-diazabicyclo[3.3.1]nonane ring system, while trigonoine B (1) was formed by a combination of 2,3-dihydroquinolin-4-one and 3H-pyrrolo[2,3-c]quinoline

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• for performing the 2D NMR spectroscopy. Funding The authors are indebted to the Department of Chemistry (Atatürk University) and the Scientific and Technological Research Council of Turkey (TUBITAK, Grant No. TBAG-110T208) for their financial support of this work.

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• enolate formation from 8h,i with s-BuLi, a deuterium quenching experiment with D2O was performed. Analysis by 1H NMR spectroscopy revealed 87 and 91% deuterium incorporation, respectively, indicating that a deprotonation occurred, but the epoxide opening was hampered by the combination of a sterically

• -diastereoselectivity and from (R)-propylene oxide (R)-7b with good 8:1 anti/syn-diastereoselectivity. This makes the following oxygenation course most likely (Scheme 7). Silylacetamides 8e–g exist as approximately 4:1 rotameric mixtures of (Z/E)-isomers as determined by 1H NMR spectroscopy at room temperature and

• extracts were dried over MgSO4 and filtered. The filtrate was evaporated and the diastereomeric ratio was determined by 1H NMR spectroscopy. The crude mixture was purified by flash chromatography (gradient, hexanes/EtOAc 10:1 to 1:1) to give lactam trans-12. Dess–Martin oxidation of hydroxylactams 12

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

• newly prepared 3-[amino(aryl)methylidene]oxindoles with primary, secondary, and tertiary nitrogen (series 5–7) has been therefore confirmed by 1H NMR spectroscopy in CDCl3 or DMSO-d6 solution. In all spectra the proton in position 4 of the oxindole moiety shows a typical upfield shift in the range of

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• is usually neglected for further investigations. Structural disturbances are also not welcome in spectroscopic studies of fluorine-labeled proteins by 19F NMR spectroscopy. Effectively, it is much better and easier to study a protein that is properly folded, rather than a protein that is misfolded