Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• irradiation of the H-4 proton resulted in a stronger enhancement of the signal corresponding to the pseudoequatorial proton H-5b (1.5%), whereas a weak NOE was observed for H-3 (0.4%) and the pseudoaxial H-5a proton (0.5%). Furthermore, the protons of the phenyl ring at C-3 were also affected (0.8%). The

• (Figure 3). Not surprisingly, the NOE between the protons H-3 and H-4 was significantly stronger (2.4%) than in the respective trans isomer 8a. The C-3/4-cis isoxazolidin-4-ols 10b and 10c were obtained from the ketones 9b and 9c in a similar manner in satisfying (51%) and good yield (72%), respectively

• NOE enhancements observed in the isoxazolidin-4-ol trans-8a. The arrows show the NOESY correlations. Selected NOE enhancements observed in the isoxazolidin-4-ol cis-10a. The arrows show the NOESY correlations. Synthetic approach towards isoxazolidin-4-ols via the regioselective reductive cleavage of

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• -diastereomers (cis- and trans-10) were separated by column chromatography, and they were identified by nuclear Overhauser effect (NOE) NMR spectroscopy. In the ROESY spectrum of the cis-diastereomer (cis-10), the phenyl 1H resonances give NOE/ROE crosspeaks with the C(4)H and one of the C(5)H2 1H resonances. By

• contrast, in the spectrum of trans-diastereomer (trans-10), phenyl 1H resonances give NOE/ROE crosspeaks with C(4)-methyl and the other one of the C(5)H2 1H signals (see Supporting Information File 1 for details). Thus, based on the distinctive NOE patterns of phenyl resonances, the two diastereomers (cis

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• possessing a Z geometry, as evinced by a NOE interaction between Hd and the methyl group. The cis relationship between the OH group and the pyrrolidine ring, resulting from the chemo- and stereoselective syn reduction of the carbonyl group, was evinced by NOESY-1D experiments showing intense NOE effects

• rod, disc and sphere, respectively. Chemical structure of representative approved drugs containing a spirocyclic moiety. Top: Selected NOE contacts from NOESY 1D spectra of compound 36; bottom: low energy conformer of 36, Z rotamer, using ab initio calculation at the HF/3-21G* level. PCA plot

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• orientation of the anomeric hydroxy group was proven by NOESY correlations between the H-2 proton and both geminal protons of the CH2P unit. A strong NOE was also observed for the upfield-shifted doublet of doublets at 1.71 ppm of the methylene group, which had an additional NOE correlation with the broad

• % yield [29]. At this stage, the Z-configuration of the enol ether was unambiguously assigned on the basis of NOESY experiments. Specifically, NOE correlations were seen between the olefinic proton and the methylene protons of a benzyl group. The position of the 2-O-benzyl group was assigned on the basis

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• = 9.5 Hz), 131.10 (d, J = 9.5 Hz), 131.61 (d, J = 98.6 Hz), 131.82 (d, J = 3.2 Hz), 131.88 (d, J = 2.4 Hz), 133.61 (d, J = 100.1 Hz); 31P NMR (162 MHz, CDCl3) δ 36.03; anal. calcd for C23H29O2P: C, 74.98; H, 7.93; found: C, 75.08; H, 7.77. NOE effects in molecules 16 and 18. Synthesis of (1R,2R,4S,5R)-3

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• electrolysis or photolysis as indicated through electrochemical analysis was further supported through NMR. Previous work [21] had conclusively shown through 1H NOE NMR spectroscopy that the LW isomers resulting from photolysis of 3a and 3b were 4a and 4b, which open toward the more electron-deficient

• heteroaromatic ring of the quinoline and away from the R group. Unfortunately, efforts to obtain a sufficient quantity of the electrogenerated LW form of 3a (i.e., 4a or 5a) for definitive 1H NMR spectra or NOE experiments were not successful However, both UV–vis and electrochemical measurements indicated small

• thermal LW forms are the same isomer 5a, while it is the pLW isomer 4a that grows in upon photolysis (Figure 3c, dashed green; Figure 5b). Furthermore, modest NOE enhancements can be observed even on the small amounts of 5a present in these solutions. These NOEs, while weak, did aid in assigning the peaks

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• strong NOE between NH(II)↔H-4 and weak NOE between NH(II)↔H-2 of ring B indicated the orientation of NH(II) towards the carbonyl group of ring A with the formation of intramolecular hydrogen bonding in a seven-membered ring leading to the γ-turn conformation (Figure 2). The involvement of amide NHs in

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• conformations. This will add an entropy penalty for the E-isomers. Interatomic distances from NOE buildup rates Interatomic distances, derived from NOE buildup rates, are summarized in Figure 7. Signal overlap prevented an analysis accounting for the presence of an ensemble of conformers such as NAMFIS [39][40

• NOE buildup experiments: gradient enhanced NOESY spectra were obtained for nondegassed solutions (16–46 mM) in CDCl3 at 25 °C, 400 MHz, mixing times = 0.1, 0.2, 0.3, 0.5, 0.7 s. The distance between aromatic ortho protons (H-6 and H-7 in Figure 9) was used as reference distance rref at 2.51 Å. Volume

• integrals for NOESY diagonal and cross peaks were measured for mixing times during the linear NOE buildup phase. For each signal pair A/B with a NOESY cross peak an average cross peak volume was calculated from measured volume integrals as: The slope σ from the plot of average volume vs mixing time was

Reversible switching of arylazopyrazole within a metal–organic cage

• Anton I. Hanopolskyi,
• Soumen De,
• Michał J. Białek,
• Yael Diskin-Posner,
• Liat Avram,
• Moran Feller and
• Rafal Klajn

Beilstein J. Org. Chem. 2019, 15, 2398–2407, doi:10.3762/bjoc.15.232

• ; rather, they suggest that 1 resides in the hydrophobic cavity of 2, interacting with its aromatic walls. Integration of the signals due to 1 and 2 confirmed that each molecule of the host encapsulates two molecules of the guest. The presence of a complex is also evident from the NOE spectrum, which shows

• protons are correlated with H1, H3, and H7, whereas the Hc protons are correlated with H4, H8, and H5 (see the partial NOE spectrum in Figure 2; see below for further analysis of this spectrum). Single crystals of (E-1)22 suitable for X-ray diffraction were obtained by slow water evaporation from an

• host is small and is mostly related to the positions of the Pd centers (Figure S16, Supporting Information File 1). We were pleased to find that the structural features of (E-1)22 resolved by X-ray crystallography were in full agreement with a detailed analysis of the complex’s NOE spectra (see Figure

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• for both isomers (4.4 Hz for A and 11.2 Hz for B) are indicative of different relative orientations of these protons and suggested that these protons in isomer B have trans-orientation, whereas those in isomer A have cis-orientation. Further, NOE between methyl and hydroxy groups for B isomer and a

• merely weak NOE for those groups in isomer A further allowed to propose a cis-orientation of these substituents for isomer B and the opposite one for A (Scheme 4). Antioxidant properties of 9, 11, 14 Among the methods for the antioxidant activity (AOA) estimation, using 1,1-diphenyl-2-picrylhydrazyl

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• determined on the basis of NOESY analysis and 3JHH coupling constants. NOE was detected between H2 and H11 but not between H2 and H4, reflecting the Z-configuration for the C2–C3 double bond. Similarly, NOESY correlations for H4/H6 and H5/H11 reflected the E-configuration for the C4–C5 double bond, which was

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• -12α. The 5,6-epoxide was determined as β by a correlation from H-6 to H-3. These assignments are in complete agreement with the relative stereochemistry of 4ß-hydroxywithanolide E (1). In irinan B, the configuration of OH-14 could not be unambiguously inferred from NOE data due to the signal overlap

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• . The 1H spectrum of 6R contains one set of sharp signals, suggesting that the [6]rotaxane is adopting a relatively rigid and symmetrical structure in solution (Figure 2a). NOE cross peaks between the triazole and CB[6] protons, and also Ha of the anthracene stoppers and CB[6] protons were observed

• , suggesting that the two CB[6] are interlocking at the triazole which is consistent with the strong binding of the CB[6] to the ammoniums (Figure S18 in Supporting Information File 1). Due to the severe peak overlapping in the aliphatic region at 3.5–4.5 ppm, NOE cross peaks in that regions cannot be

• elucidating the origin of the stereoselectivity in the synthesis of 6R. The 1H spectrum of 4R is generally similar to that of 6R and strong NOE cross peaks between the triazole and CB[6], and also Ha of the anthracene and CB[6] protons were observed (Figure S10 in Supporting Information File 1), confirming

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• and 18. Additionally, nOe studies on 17 confirm the stereochemical assignment. Conversion to mesylates 19 and 20 using mesyl chloride and triethylamine was straightforward. Mesylate 19 reacts readily in CD3CO2D at 20 °C (Table 1) to give the substituted cyclobutyl acetate 21 (92%) as the major product

• borohydride reduction of the ester functionality of 63 gave a separable mixture of alcohols 64 and 65. The stereochemistry of the product 65 was established using nOe studies. Cyano to carbomethoxy conversion in 65 to give alcohol 66 was straightforward. Triflate derivatives 67 and 68 were prepared since

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• GalNAc and a carbonyl oxygen in the peptide main chain [33]. These conclusions had been based on the intensity of the observed NOE signals between main chain amide protons and α-protons. They conclude that the presence of strong NOE signals between Hαi and HNi+I protons (dHαi−HNi+1) together with the

• weak one between HNi and HNi+I protons (dHNi-HNi+1) or similar intensity of NOE signals between Hαi and HNi (dHα−HN1) as well as HNi+I (dHαi−HNi+1) is a sufficient evidence for the presence of the extended structure. However, a similar analysis of the determined NOE interactions did not provide enough

• peptide 3 (see Table 3 and Figure 4). Such situation is the result of numerous well defined intra- and interresidual NOE signals of sugar moiety protons (see Table S6, Supporting Information File 1). Although the orientation of the galactose ring is highly ordered, as shown the value of the temperature

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• spectrum of 1. Cañedo and co-workers had previously reported a (14R,15S,17R,19S) relative configuration for 2 [18]. As opposed to the NMR analysis of 2, we detected only a weak NOE correlation between H-14 and H-15. Furthermore, strong NOEs were observed from the N-methyl protons (H3-18) to both, H-17 and

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• allows to correlate the exchanging signals in both slow and fast exchange regimes. The measured ROESY spectrum featured both NOE interactions of the opposite phase and EXSY peaks of the same phase as diagonal peaks. The EXSY cross-peaks indicate the chemical exchange between methylene protons (H4), the

• aromatic protons (H1) and methyl protons (H6, Figure 4). The NOE interaction between the glycoluril methine protons (H5) and aromatic proton (H1, Figure 4) also confirmed the assignment of 1a-1. The integration of signals in 1H NMR spectra at −40 °C revealed uneven populations of conformers in a 4:3 ratio

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• imines 99 to furnish complex spirocyclic γ-lactams 101 (Scheme 29) [107]. These products show a trans orientation of the benzene moiety in the isoindolinone and the substituent in R2, according to NOE experiments and crystal structure analysis. The proposed mechanism involves an initial palladium

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• -oriented. Besides, the trisubstituted olefin (Δ3/15) was determined to be in E configuration due to the clear NOE correlations of H-15 with H3-13 and H3-14. In view of the above evidences, the relative configuration of compound 1 was determined as 1R*,2R*, the same as 1a [16][17]. Compound 2 was isolated

• ], was established by HR-ESIMS ion peaks at m/z 370.9654, [M − H]− (calcd for C15H17OBr2, 370.9646). The 1H and 13C NMR data of 4 were identical to those of 4a, a C-10 bromonated analogue of 3a. In addition, the NOE correlations between H3-13 (δH 1.21, s) with H-2 (δH 3.34, q, J = 7.3 Hz) and H-5a (δH

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• -hydroxy esters 9, 10 and 11 (dr = 1.74:0:38:0.24) in a total yield of 84% (Scheme 2). Gratifyingly, the percentage of derivatives 9 and 10 that show the desired stereochemistry at carbon center 5a is around 90%. The structure of all these isomers was confirmed by NOE experiments (see Supporting

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• moiety had clear correlations with the double bond carbons (δc 132.8, s, αC and δc 123.3, d, βC), and the βH exhibited clear HMBC correlations with the αC and carbonyl carbon (δc 168.8, s, CO). These NMR data clearly indicate the presence of a dhThr moiety (Figure 3), and the strong NOE between the γCH3

• amino acid sequence of cichorinotoxin; the NOESY data are shown in Figures S10A–S10F (Supporting Information File 1), and the HMBC data are shown in Figures S12A–S12C. Figures S10B and S10C highlight the NOE correlations of αNiH/αNi+1H. Figures S10D and S10E mainly depict the NOE correlations of αNiH

• , COSY and NOESY spectra of the tetraacetate are shown in Figures S13E–S13N (Supporting Information File 1). The NOE data indicated that the amino acid sequence of the tetraacetate is as shown in Figure S14 (Supporting Information File 1). The positions of the acetates were determined mainly from the

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• , one of the N-aryl substituents was replaced with the smaller methyl group. Complex 164 was obtained in poor yield (30%) and characterized through NOE and X-ray analysis, revealing the exclusive formation of the rotational isomer in which the N-methyl lies over the carbene unit (the syn isomer, Figure

• case of 172, the Hoveyda-type analogue of 164 (Figure 32), for which a room temperature interconversion between syn and anti rotamers, observed at a ratio of 7.8:1, was revealed by NOE experiments. Surprisingly, despite such rotation the reactivity profiles and the enantioselectivities observed for 164

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• reaction described in this work occurred with high atom efficiency (atom economy of 90%) and produced only stoichiometric H2O as waste (E-factor of 0.1). Stereochemistry and mechanism The stereochemistries of 5a–m were ascribed by NOE NMR experiments. By example using 5a depicted in Figure 2, the 1H NMR

• spectrum showed that H(1) appears at 5.95 ppm as a singlet and H(4) at 4.72 ppm as a quadruplet. No distinct NOE effect was observed between H(1) and H(4), when either H(1) or H(4) was irradiated. A significant positive NOE effect was observed between H(1) and H(20). Thus, NOE analysis assumed that H(1) is

• between H(1) and H(4) in the NOE experiment. The structure contains two carbonyl moieties C(6)–O(2) and C(3)–O(1) with similar distances of 1.222 and 1.218 Å, respectively. The intramolecular hydrogen bond O(1)–H(13) remains strong in the nitrogenated tricycle (2.579 Å) vis-à-vis of the starting hydrazide

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• . For example, in the 2D NOESY spectra of host–guest mixture of 2,2’-CBP4 and B, NOE correlations were clearly observed between the middle protons H1 and H10 of B with the methylene Hc of 2,2’-CBP4, and between the aromatic protons (Hb) of 2,2’-CBP4 and H2 of B (Supporting Information File 1, Figure S11

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• ), H11 (peak C) (around the DBA recognition site) and methylene protons on the functional crown ether indicate that the DB24C8 macrocycle was located on the DBA site, corresponding to the structure of [2]rotaxane R1. After addition of 2 equiv DBU to the solution of R1, the NOE correlations between the