gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• importantly, the application of 8 equiv of tert-BuLi induced the formation of N-methylation products (Scheme 6). Compounds 15a (15a’) and 16a (16a’) existed as two rotamers, in ratios of 1:1.15 and 1:1.76, respectively, with the predominant cisoid isomer. Transoid (trans 15a(16a)) isomers contained a larger

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• the minimum geometries are reported, as no transition states were obtained because the carbocation ring formation is a spontaneous process. Moreover, it is noteworthy that for each cation optimized, we examined several other conformers (specifically rotamers), but these were of higher energy than the

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• 4.95 ppm with a J value of 3.6 Hz in the 1H NMR spectrum proving the anomeric α-configuration. The presence of Troc-rotamers was also apparent, with a ratio of 19:6 being observed by 1H NMR in CDCl3 at 25 °C. Catalytic amounts of NaOMe (0.005 M) in MeOH were used to remove the acetate from compound 4

• choice [12], surprisingly better than a benzoylated donor [19], why this donor was the first one tested also with the quite different acceptor 5. An NIS/AgOTf-promoted glycosylation with donor 6 [20] yielded 79% of disaccharide 7. Due to the presence of rotamers, NMR spectra of 7 proved to be difficult

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

• , and 1H/13C NMR spectroscopy. Proton NMR shows a complicated set of overlapping multiplets indicating that the reaction results in the formation of various isomers (rotamers) which are different by relative orientation of the benzoguanidine donor moieties with respect to each other (Figure 2, see

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• feasible under these conditions, the observed reaction efficiency was poor (14–33% yield). However, on the 1H NMR spectrum, some unexpected signals were observed. The appearance of equilibrating species such as rotamers in the 1H NMR spectrum (see the variable-temperature NMR experiments in Supporting

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• electron-rich salt 5al was obtained in 75% yield using modified reaction conditions B. The harsher conditions were probably required due to a sterically hindered rotation of the benzimidazole moiety in the plane of the iodophenyl, which could also be observed in two rotamers of the starting iodoarene 4al

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• cage nitrogen atoms) and/or rotamers (restricted rotation around amide C–N bonds), which is well-known for amides and carbamates (Figure 4a). The activation barriers for the rotation across amide C–N bonds in 4a and 4c estimated by DFT (18.4 and 19.4 kcal/mol, respectively, ωB97XD/Def2TZVP, gas phase

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• and trans-amide rotamers using NOESY experiments (Figure 4 and Supporting Information File 1). Specifically, in DMSO-d6, the predominant rotamer of monomer 1 is characterized by a NOE cross-peak between the acetyl methyl group and side chain methyl group, indicative of a trans-amide bond geometry. A

• , dimer 2 and trimer 3 showed similar correlation patterns to those observed in the monomer involving two and three trans-amide bonds, respectively, for the predominant rotamers (Figure 4 and Supporting Information File 1). We could also show that the two amides of dimer 2 have approximately the same cis

• /trans ratio, at least in CDCl3 and CD3OD. This suggests that the same may be true for longer oligomers. As the oligomer elongates, shoulders that may represent different rotamers in small proportions appear in the NMR spectra, but one isomer remains present predominantly. More specifically, in the case

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• their syn- and anti-orientation is present in the molecule [45][46]. Ley et al. demonstrated that selective chemical exchange NMR experiments are very useful in the determination of equilibrating rotamers, including chiral N-Boc amino acid derivatives, from non-equilibrating diastereomers [47]. Chemical

• ppm appeared, implying chemical exchange and therefore the presence of rotamers (Supporting Information File 1 in Figure S53b). The synthesis of methyl 5-(N-Boc-piperidin-4-yl)-1,2-oxazole-4-carboxylate (4h), a nonchiral amino acid-like building block, was obtained by the reaction of β-enamino

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• formation of micellar aggregates in water, they were very difficult to recrystallize. These two experimental facts supported the employment of a metallosurfactant definition to the complexes described here. Rotamers of the ligands L1–L3 observed in the 1H NMR spectra disappeared in large extension after

• ligand rotamers were considered during the optimization process. Only one enantiomer was selected for running the calculations for simplicity. The obtained results are gathered in Figure 1 and Figure 2. These calculations show that for ligands L1 and L3, conformer A and conformer B, resulting from a free

• signals in NMR spectra (corresponding to conformer A) would be observed. For L1-Pd complexes, the aggregate included two energetically accessible rotamers at room temperature (energetic difference of +2.2 kcal·mol−1, Figure 1). Therefore, the duplicated set of signals in the 1H NMR was justified. We

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• mixture of two rotamers in a ≈2:1 ratio at 25 °C, probably caused by the Cbz-protecting group (see Supporting Information File 1, page S26). It is worth mentioning that the attempts to prepare polyhydroxylated pyrrolidine 2 directly from epoxide 5 by the one pot Cbz-removal/aminocyclization under

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• , nonproductive dimeric aggregates form under standard reaction conditions. These dimers exist in different combinations of the thiourea rotamers and lead to competing catalytic pathways (Scheme 16a). Moreover, anion abstraction was calculated to proceed either through a 4H abstraction mechanism of two thioureas

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

• proline is the comparatively similar intrinsic stability of the amide rotamers in the peptidyl-prolyl fragments. Usually, a peptide bond exhibits a high preference towards the trans-amide, represented by a dihedral angle ω of 180°. In peptidyl-prolyl, however, trans- and cis-conformations (ω = 180° and 0

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• rotamers (in CDCl3). Rf 0.50 (pentane/ethyl acetate 1:1); mp 92–102 °C; IR νmax: 2244m, 1738m, 1688s, 1394s, 1163s, 1119m; 1H NMR (400 MHz, CDCl3) δ 1.40 (s, ≈1.5H), 1.41 (s, ≈1.5H), 1.43 (s, ≈3H), 1.47 (s, ≈3H), 1.49 (d, J = 7.0 Hz, ≈2H), 1.51 (2 × d, J = 7.0 Hz, 2 × ≈0.5H), 1.83–2.43 (m, 4H), 3.39–3.62

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

• rotamers in hand, an Eyring plot was generated, and the enthalpy and entropy of activation were derived (Table 2). The structural identification of the major and minor rotamers was not attempted by NMR, but in silico investigations of 3a supported the intuitive notion that the rotamer of lower energy was

• rotamers. By comparison, ΔH between the two rotamers was obtained experimentally by fitting the van ‘t Hoff equation to the population differences observed in the 19F NMR spectra between 224 and 264 K. 0.89 kcal⋅mol−1 is in tolerable agreement with the computation. Comparing 3a, 4a, 4b, and 6a in Table 2

• , the enhanced imbalance in the population of the rotamers of 6a is notable and consistent with the amino moiety imposing a greater steric hindrance. The differences among the other compounds are more modest. The small entropy of activation is consistent with a simple rotation over a steric barrier

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• us to propose the hypothetical analog 2 (Figure 1) as a potential mimic of 1. The analog 2 contains a saturated alkyl chain with two vicinal C–F bonds in the α/β positions relative to the amide moiety. The presence of a vicinal difluoride moiety within an alkyl chain is known to favour rotamers in

• which the C–F bonds align gauche (I and II, Figure 1) [22]. Separately, the presence of fluorine on the α-carbon of a tertiary amide is known to restrict the Cα–C(O) bond to a small set of low-energy rotamers (III–V, Figure 1) [23]. Intriguingly, studies of simple molecules containing either F–C–C–F or

• F–C–C=O motifs have shown that the rotamer populations can change, depending on the polarity of the solvent [22][23]. The rotamers I and IV (Figure 1, boxed) would appear to provide the closest structural match with compound 1, but in a highly polar medium the more polar rotamers II and V might

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• minimisation and generates rotamers which can be visualised using JSmol viewer. Information about the force field that is used to build the structure is also provided. The multiple structures can be downloaded compressed as .tar, .gz or .zip files containing .pdb files. Similarly, the 2D image can be saved in

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• protein chemistry. The peptide bond can exist in two discrete states, commonly designated as trans- and cis-rotamers (ω = 180 and 0°, respectively). The cis-peptide bond is very rare in natural proteins [79], except for the cases when it precedes a proline residue. The secondary amino group of proline

• its analogues towards trans- and cis-amides [81]. An unsubstituted proline residue usually exhibits a preference to form a trans-amide. Fluoroprolines are notorious for the relative stabilization of the amide rotamers depending on the stereochemistry at the C4-atom. This is known as the chiral bias

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• annulation was favorable for the formation of six-membered rings. Nevertheless, the existence of several rotamers of 1 derived from the restricted rotation of the peripheral phenyl ring substituents and its nonplanar geometry prevented the structure elucidation by proton NMR analysis [35]. Single crystals of

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• smoothly reacted affording product 9 in good yield under reaction conditions identical to those for the unhindered primary amines (5 min, 60 °C). Consistent with previous NMR studies of secondary amides, each of these were observed as a resolved mixture of the s-cis and s-trans rotamers [19]. Product 16

• obtained from N-methylbenzylamine was found to be a near 1-to-1 mixture of rotamers, while product 9 from 2-(methylamino)ethanol appeared as a 2-to-1 mixture favoring the s-cis form. Another noteworthy entry from Table 2 was methyl 2-aminomethyl-5-furanoate (for 14). As the DBU amidation relies on an

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• (Table 1, method A, entry 1), was unexpectedly found to be O-benzyl benzylcarbamothioate (4a). The spectral data indicated that the product existed in cis- and trans-geometrical isomeric forms (rotamers) because of free rotation along the thioamide bond. When the same reaction was conducted in other

• the carbamothioate products obtained indicated that, apart from 4e and 4f, all existed as rotamers and that the ratios of rotamers, where present, were the same whether derived from either method A or B. Alajarin et al. [32] noted a similar doubling of 1H and 13C NMR signals due to rotamers in one of

• -311++G(d,p) level of theory, with solvent corrections for chloroform, for two rotamers, namely 4cA and 4cB (generically represented as 4A and 4B in Figure 3). These structures were generated based on the X-ray structure of 4c and afforded a computed Gibbs free energy difference of −1.769 kJ mol−1 in

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• the kinetic rate of the equilibrium between 18a and 18b, making both rotamers observable in the 1H NMR spectra. Conversely, after deprotonation of the ammonium moieties the macrocycle 18a is forced to adopt a helix-type contracted conformation (two slowly interconverting rotamers 18c and 18d) with a

Synthesis of 9-O-arylated berberines via copper-catalyzed C_Ar–O coupling reactions

• Qiaoqiao Teng,
• Xinhui Zhu,
• Qianqian Guo,
• Weihua Jiang,
• Jiang Liu and
• Qi Meng

Beilstein J. Org. Chem. 2019, 15, 1575–1580, doi:10.3762/bjoc.15.161

• range of 4.00–2.00 ppm, and they are diastereotopic due to the restricted rotation of the hydroquinolizine rings. Both anti- and syn-rotamers were observed in a ratio of 3:1 in the 1H NMR spectrum of compound 4. As the quaternary ammonium unit is essential for biological activity, compounds 2a–o and 4

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• –H (M06-2X/aug-cc-pVDZ) shows that each conformer has three lower-energy rotamers, identified according to the orientation of the nitrogen lone pair as anti (a) and gauche (gX and gH) to H1 (Figure 3). Optimization and frequency calculations were performed for these rotamers at different theory

• this theory level to describe the studied systems. The agreement of the energy values in gas phase with those in solution confers reliability to calculations such as natural bond orbitals (NBOs), which are made in the gas phase. With regard to rotamers, gX in ae conformer and a in ea are the least

• stronger effects. In Table 4 only the most stable rotamers for each conformation were analyzed. The values of ΔEdeloc show an inversion of the conformational preference for all compounds in the absence of hyperconjugative interactions, and ae becoming the most stable conformer. It is worth noting the