An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• /AcOH) gave 5i as a white foam after co-evaporation with toluene (80%): TLC Rf = 0.2 (1:1:0.02 hexanes/EtOAc/AcOH); IR (thin film) ν 3331, 3035, 2933, 1715, 1497 cm−1; 1H NMR (400 MHz, CDCl3) two rotamers, δ 1.43 (s, 1.2H), 1.45 (s, 1.2H), 1.51 (s, 1.8H), 1.55 (s, 1.8H), 1.74–1.79 (m, 1H), 2.03–2.07 (m

• , 1H), 2.84–2.87 (m, 4H), 2.98–3.08 (m, 1H), 3.15–3.20 (m, 1H), 4.44–4.50 (m, 0.4H), 4.57–4.62 (m, 0.6H), 4.84 (s, 0.4H), 5.02 (s, 0.6H), 5.17–5.18 (m, 1H), 6.47 (bs, 1H), 7.18–7.28 (m, 5H) ppm; 13C NMR (100 MHz, CDCl3) two rotamers, δ 24.8, 25.1, 26.2, 31.2, 38.1, 39.3, 54.6, 57.5, 83.2, 84.3, 127.2

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• ΔE values for the rotational diastereomerism decreased (i) with the decrease of the steric hindrance between the three (hetero)aryl rings in rotamers (s–s) > (a–s) > (a–a), and (ii) with the weakening of the π-deficiency of the s-triazine, 2a > 3. The same optimal geometry (a–a) was found in

• duplicate, (a–a)/(a–a), in G-1 dimers D-Cl and D-N

  NH (Figure 2). Furthermore, for the major (a–a) rotamers, calculations also revealed high solvation energies in the case of all four G-0 and G-1 dendrons. For a single compound, the solvation energy was 33–40% higher in THF vs 1,4-dioxane. Unsurprisingly

• ascribed the low reactivity of G-1 dendrons D-Cl and D-N

  NH in our SN2-Ar amination conditions to the increased solvation of their (a–a)/(a–a) rotamers (+140–170%, i.e., more than double) compared to those of the (a–a) rotamers of G-0 3 and 2a. In addition to all the above, due to the steric

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• 271 K (300 ms mixing time), proving that the two forms interconvert in a slow exchange regime on the 1H NMR time scale. This equilibrium was ascribed to the existence of the syn- and anti-rotamers of the carbamate group. The more stable forms (about 85% population at 271 K) were assigned to anti

• -rotamers based on literature results [25]. Different NMR parameters were examined to analyze backbone conformational propensities, namely 1Hα and 13Cα chemical shift deviations (CSD), vicinal 3JHN-Hα coupling constants, Hα-HN ROE correlations and temperature coefficient (ΔδHN/ΔT) of the amide protons. The

• between 8.6 and 9.1 Hz). We next examined the values of vicinal 3JHα-Ηβ coupling constants which yield information on side-chain χ1 dihedral angle space (Table 4) [34]. Most residues exhibit average values that indicate conformational equilibria between different side-chain rotamers. Notably, the (2S,3S

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• , which requires the differential solvation of two rotamers. This differential solvation may be explained by the polarity of the two rotamers; thus, the polarity model expressed in Scheme 3 cannot be dismissed. Additional factors, such as multipolar interactions [77] and especially the polar surface

• the accuracy was defined by the length of the time domain spectrum at approximately 0.3 Hz. The semi-empirical calculations were performed by using the PM6 algorithm from the MOPAC package. DFT geometry optimization of the 5 amide rotamers was performed using B88-PW91 GGA with the DZVP basis set

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• free rotation about the sn-1,2 and sn-2,3 C–C bonds furnishes nine conformers by the combination of three staggered rotamers, namely gt (gauche–trans), gg (gauche–gauche) and tg (trans–gauche, Figure 1). Conformational flexibility often leads to the ambiguous characterization of acyclic molecules

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• ). Unfortunately, we observed two signal sets in NMR spectra (intensity 3:1) for the product which could not be attributed to conformers or rotamers as evidenced by variable temperature and NOESY NMR experiments. These results, and the fact that Cochrane also reported problems due to epimerization during

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• and contained broadened signals, suggesting the presence of other rotamers in CDCl3 solution. The mechanism of the formation of nitrile 5 in the reaction under study here is so far unclear. The control experiment showed that under reaction conditions the secondary thioamide 3o undergoes transformation

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• , 49.0 ppm) are found when analyzing the 13C NMR spectra. Two effects are responsible for this behavior. The first arises from the presence of two different conformers (rotamers); this is caused by the limited interconversion by rotation about the C–N amide bond resulting from the partial double bond

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• -caprolactam of N-Boc-trans-4-hydroxy-L-proline methyl ester 5b, rotamers due to flipping of the N-Boc group were obtained. Owing to the importance of sugar caprolactams in polymerizations, 2,3-di-O-benzyl-4-O-p-methoxybenzyl-α-methyl-D-glucopyranoside and 2,3,4-tri-O-benzoyl-α-methyl-D-glucopyranoside [30][31

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• removed and the intermediate amine 9 was condensed with 2a to afford the corresponding glycosylated AEG dipeptide 4 in 58% yield. All glycoconjugate building blocks showed the presence of cis and trans rotamers. Compounds 1a, 1b and 4 were subjected to temperature dependent 1H NMR spectroscopy in order to

• determine the coalescence temperature which resulted in calculated rotation barriers of 17.9–18.3 kcal/mol for the rotamers. Keywords: amino acids; carbohydrates; glycoconjugates; glycopeptides; N-(2-aminoethyl)glycine; Introduction The glycocalyx is a fringy or fuzzy polysaccharide layer coating most

• -dependent 1H NMR spectroscopy. Unfortunately, the amidic protons of the rotamers of the unprotected glycoconjugates could not be observed in the 1H NMR spectra in D2O due to the fast H/D exchange with the solvent (Figure 2). Nevertheless, we could identify two rotameric forms exhibiting a cis/trans ratio of

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• exploration of the potential energy surface (PES) at the M06-2X/6-31+G(d) level of theory, four local minima were located for each system, namely: gauche_s-cis, gauche_s-trans, anti_s-cis and anti_s-trans (Figure 4) [24]. In the gauche rotamers (the most stable found in each system), the phenoxy and acrylate

• conformational change can be responsible not only for the broadening of the NMR signals of some nuclei at room temperature, but also for the NMR splitting observed upon cooling. In the gauche conformers a significant shielding of the vinyl protons is expected, while in the anti rotamers those nuclei should not

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• structures (see Experimental section). The half-chair (C2) arrangement was found to be the only stable conformer for the 1,3-dioxolane ring with all other conformers being rotamers about the C(2)–CH2R and C(2)–OMe bonds [where R = H (5) or t-Bu (16)]. The orientation of the C(2)O–Me group is ignored from

• this point as it does not substantially affect the relative energies of the C(2)─CH2R rotamers. The potential energy surface for 16 is dominated by the syn arrangement of R with respect to the OMe group (16a and 16b in Figure 5; ΔΔH = 0 and 0.8 kJ/mol, respectively); the rotamer which orients the R

• was any enthalpic barrier to elimination of the protonated methoxy group, geometric scans for potential transition-states were made using Density Functional Theory calculations, by incrementally increasing and fixing the C(2)─OMe bond length for rotamers 16a–c after protonation, and allowing all other

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• association or the relative population of rotamers [50]. In the current study these forces coexist with other ones in the same molecule. Results and Discussion Studies by NMR techniques Properties of 1 The dilution studies for 1 provided its self-association constant Kself = 170 M−1 (CDCl3, rt, Supporting

• between forms/rotamers involved in intra- and intermolecular hydrogen bonding of similar strength. Probably the Kassoc is an order of magnitude higher for the more stable complex and this corresponds to the titration data from ca. 0.6–0.7 [2–9]:[1] ratio to infinity. That is understandable since 1e may

• 1H NMR spectra were recorded in CDCl3 dried over molecular sieves. For this purpose three benzoates 2, 5 and 8 and naphthyridine salt 10 were used. Since some of discussed complexes/rotamers are nonsymmetric the numbering of atoms in 1 is from 1 to 14 although the rotamers 1a or 1e shown in Figure 2

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• UB3LYP/6-31+G(d,p) optimized structures of compounds and their radicals in the gas phase are given in Table 2. For all monomers only rotamers with intramolecular hydrogen bonds between the hydroxy and the methoxy groups (O atom) are considered. In case of monomer 4 the structures with hydrogen bonds

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• rotamers for both molecules as well as the effect of adding a centre of inversion to each of these. The disordered models assigned were consistent with the observed difference Fourier electron densities, in particular those of the hydrogen atoms, whose relative values indicated that the sites of their

• crystallographically unique, weak C–H…N hydrogen bond. In the centrosymmetric structural model for 4-(4-pyridyl)pyrimidine (8) (Figure 4c), atom N4 is necessarily present with s.o.f. = 1, but the evidence from the X-ray analysis indicated the presence of rotamers, with both the 2- and the 6-positions in the two rings

Interactions between tetrathiafulvalene units in dimeric structures – the influence of cyclic cores

• Huixin Jiang,
• Virginia Mazzanti,
• Christian R. Parker,
• Søren Lindbæk Broman,
• Jens Heide Wallberg,
• Karol Lušpai,
• Adam Brincko,
• Henrik G. Kjaergaard,
• Anders Kadziola,
• Peter Rapta,
• Ole Hammerich and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2015, 11, 930–948, doi:10.3762/bjoc.11.104

• [11][12] have shown how rotamers can indeed influence the electronic coupling in bis-ruthenium complexes separated by oligoynediyl spacers. In addition, an increased interaction between redox centres upon linking them together in cyclic structures was previously observed in ferrocene-dimers [13]. Here

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

• Matthieu Jouffroy,
• Rafael Gramage-Doria,
• David Sémeril,
• Dominique Armspach,
• Dominique Matt,
• Werner Oberhauser and
• Loïc Toupet

Beilstein J. Org. Chem. 2014, 10, 2388–2405, doi:10.3762/bjoc.10.249

• readily reformed in the presence of water. HUGPHOS-2 was further opposed to [RuCl2(p-cymene)]2. This reaction gave a 57:43 mixture of the two rotamers 7 and 8, which could be separated by column chromatography (Figure 3). Careful examination of the ROESY spectrum of 7 indicates that the rotations about

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• resonance. This brings, in addition to the lack of basicity, the existence of two amide rotamers A and B (Figure 8), which can be observed in NMR spectra as two sets of signals. The ratio of A:B is about 1:1 with a slight excess of rotamer B (see the Experimental and Supporting Information File 1). The

• existence of the two rotamers prompted us to estimate the energy barrier of their interconversion. We therefore performed variable 31P NMR measurements of 14 at different temperatures (starting at 25 °C with a 10 °C step, with the last measurement taken at 100 °C) and a line-shape analysis of an uncoupled

• the entropy of activation ΔS‡ = −190.6 J/(K·mol) (for details, see Supporting Information File 1). The relatively low value of ΔG‡298 = 80.7 kJ/mol implies that the preparative isolation of the individual rotamers A and B at room temperature would not be possible. For the purposes of conformational

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• .10.63 Abstract Surprisingly stable formamide rotamers were encountered in the tetrahydroisoquinoline and morphinan series of alkaloids. We investigated the hindered rotation around the amide bond by dynamic high-performance liquid chromatography (DHPLC) and kinetic measurements of the interconversion of

• the rotamers which can readily be separated by HPLC as well as TLC. The experimental results of the different methods were compared to each other as well as to results obtained by DFT calculations. Keywords: amides; density functional calculations; dynamic HPLC; rotamers; thermodynamics

• ; Introduction The hindered rotation about the amide bond belongs to the most classical concepts taught to every undergraduate chemistry student. However, amide rotamers are generally classified as conformers which interconvert at ambient temperature unless a significant steric hindrance has to be overcome. This

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• , 8H), 2.73–2.53 (m, 4H), 2.52–2.29 (m, 4H), 2.12 (s, 3H), 2.05–1.99 (m, 6H), 1.97 (s, 3H), 1.76–1.50 (m, 4H); 13C NMR (100 MHz, CDCl3) (mixture of rotamers) 175.0, 173.1, 172.9, 170.7, 170.4, 170.2, 169.9, 156.9, 143.9, 143.9, 141.4, 141.4, 127.9, 127.2, 125.2, 125.1, 120.2, 120.2, 84.1, 74.5, 72.0

• (100 MHz, CDCl3) (mixture of rotamers) 175.3, 175.2, 174.9, 174.8, 173.1, 172.9, 170.4, 170.1, 170.1, 157.3, 156.9, 143.9, 143.9, 141.4, 141.4, 127.9, 127.2, 125.2, 125.1, 120.1, 120.1, 82.3, 71.8, 71.3, 69.7, 67.3, 67.0, 48.5, 48.2, 47.3, 46.2, 45.9, 40.1, 39.8, 39.2, 38.6, 32.6, 32.4, 31.1, 30.8

• –3.56 (m, 1H), 3.51–3.17 (m, 8H), 2.76–2.52 (m, 4H), 2.50–2.28 (m, 4H), 2.02 (s, 3H), 2.00–1.95 (m, 6H), 1.89 (d, J = 9.1 Hz, 2H), 1.75–1.42 (m, 2H); 13C NMR (100 MHz, CDCl3) (mixture of rotamers) 174.8, 174.7, 173.2, 171.2, 171.2, 171.1, 170.1, 169.5, 169.5, 157.2, 157.0, 143.8, 141.3, 127.9, 127.2

Synthesis of axially chiral gold complexes and their applications in asymmetric catalyses

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 2224–2232, doi:10.3762/bjoc.9.261

• structures clearly revealed the presence of a weak gold–π interaction between the Au atom and the aromatic rings in these gold complexes. Because of the gold–π interaction, the C–N bond could not rotate freely, giving two diastereomeric rotamers (S)-15a and (S)-15b. Slaughter and co-workers have also found

• two rotamers in gold complexes 1 caused by the handicap of C–N bond rotation on the basis of X-ray diffraction and named them as “out” rotamer and “in” rotamer [49] (Scheme 5). Their energy barrier has been also disclosed by DFT calculations. Synthesis of the P–Au(I) complexes. The synthesis of the Au

• = 1525.9(2) Å3; space group: P2(1); Z = 4; Dcalc = 1.626 g/cm3; F000 = 732; final R indices [I > 2sigma(I)]: R1 = 0.0231; wR2 = 0.0538. Synthesis of compound 9. Synthesis of N-heterocyclic carbene precursor. Synthesis of benzimidazolium salt (S)-14. Synthesis of carbene Au complexes. Rotamers of 1a and 1b

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• (C-2) ppm; HRMS (ES): [M + Na]+ calcd for C19H19N5NaOS, 388.1203; found, 388.1206. N4-Benzyl-N6-butyl-2-methylthio-5-nitrosopyrimidine-4,6-diamine (6ee): Blue solid; yield 89%; mp 82–84 °C; IR (KBr): νmax 3249 (NH) cm−1; NMR spectra contain signals of two rotamers. 1H NMR (400 MHz, CDCl3, 25 °C) δ

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• resolved their structures by single-crystal X-ray diffraction. The diazoacetamides 3d and 3f crystallised as their (Z)-rotamers. These data have recently been reported [42][43]. The diazoacetamides were brominated at −5 °C with NBP in the presence of DBU and passed through a dry-ice-cooled plug of silica

High-spin intermediates of the photolysis of 2,4,6-triazido-3-chloro-5-fluoropyridine

• Sergei V. Chapyshev,
• Denis V. Korchagin,
• Patrik Neuhaus and
• Wolfram Sander

Beilstein J. Org. Chem. 2013, 9, 733–742, doi:10.3762/bjoc.9.83

• 11 the azido groups in ortho-positions to the fluorine atom should be the most photoactive. The photodissociation of the azido groups in triazide 11 can be modeled by computational methods [8][34]. Thus, for instance, the geometry optimizations of the most stable rotamers 11a and 11b in their lowest

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• -PEO3-Biotin. It should be noted that in each of the products (2b, 2d, 2f, 2h) derived from 1a it was not immediately clear whether these were a mixture of two compounds or rotamers, despite the seeming unambiguity in the synthesis. While HPLC showed a single homogeneous peak, the NMR spectrum was very

• rotamers was present and not a mixture of two compounds. Additionally, intermediate 3 also demonstrates a complex NMR spectrum indicative of the presence of two rotamers. All of this shows that, unlike the proton, the isopropyl group is bulky enough to hinder rotation of the tertiary amides and to enable

• identification of two rotamers by NMR [22]. Biological evaluation of the biotinylated Hsp90 probes As indicated above, there are several requirements for a biotinylated probe to be useful in dissecting Hsp90 tumor biology in live cells. First, the probe should retain selective and tight binding to tumor Hsp90