Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• formation [12][13][14], Diels–Alder reaction [15][16] or the imine/oxime condensation [17][18]. These reactions tend to produce strong covalent interactions between the surface and the molecules in solution which ensure a stable immobilization. One limitation of the covalent strategy lies in the

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• according to the proposed reaction mechanism. In 2015, Jiao and co-workers employed an oxime methyl ester as directing group and achieved the hydroxylation of arenes [67]. The reaction used Pd(OAc)2 as catalyst, PPh3 or DEAD as ligand and oxone as oxidant, affording the corresponding phenols in gratifying

• hydroxylated oxime could be readily converted to o-acylphenol or o-aminomethylphenol. In 2016, Sunoj and co-workers disclosed the first meta-hydroxylation of arenes using a tethered -CN directing group [68]. The conversion proceeded at 70 °C in hexafluoro-2-propanol (HFIP) in the presence of Pd(OAc)2, PhI(TFA

• hydroxylation of benzimidazolylarenes. Dioxane mediated hydroxylation of 2-heteroarylarenes. Hydroxylation of oxime methyl ester. CN-directed meta-hydroxylation. Pd(OAc)2-catalyzed hydroxylation of benzoic acids. Pd(OAc)2-catalyzed hydroxylation of biaryl or aryl alkyl ketones. Pd(OAc)2 and Pd(TFA)2 catalyzed

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• ] studied the pros and cons of a benchtop NMR instrument at 45 MHz (Pico Spin-45). For this purpose, they studied reactions like the Fisher esterification, Suzuki reactions, and oxime formation and they analyzed the samples by simple injection of aliquots in the inlet port through an HPLC filter using non

• . [45], who developed a micro-channelled cell for synthesis and monitoring (MICCS) (Figure 8) and this was integrated into a 500 MHz NMR instrument. The system was used to elucidate the mechanism of the radical addition to an oxime ether with triethylborane (Scheme 1). The use of the NMR micro flow cell

• (a) 9 s and (b) 3 min. Stoichiometry: benzyl alcohol/DIPEA/acetyl chloride 1:1:1.2. Reproduced with permission from reference [44]. Copyright 2009 The American Chemical Society. a) Design of MICCS and b) schematic diagram of MICCS–NMR [45]. CH2Cl2 solutions of oxime ether and triethylborane were

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• microwave assistance (Scheme 1). Thionation of the 4-position of 1, 4, 6, 10, 13 and 15 using P4S10 in pyridine under reflux conditions gave the 4-thiones 2, 5, 7, 11, 14 and 16 in yields between 60–80%, respectively (Scheme 1). The HHQ-oxime (3) was synthesized from HHQ (1) by conversion in the benzyl

• -protected chinolinol form (3a) and oximation with hydroxylamine hydrochloride similar to the described method used for the synthesis of the PQS-oxime 12 [33]. The entire compound library of HHQ and PQS analogues is presented in Figure 4. Further details on the syntheses are given in the Supporting

• HHQ (2, 5, 7) or PQS (11, 14, 16) scaffold or an oxime group in position 4 (3 and 12). The eight active compounds were tested in a concentration-dependent experiment in order to assess their potency in inhibiting probe binding. Interestingly, the HHQ derivative 3 with an oxime group was significantly

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• of a disfavored 5-endo-trig cyclization for the corresponding intermediate oxime. Path 2 involves the initial transformation of hydroxamoyl chloride to a nitrile oxide, followed by concerted cyclization to triazolines 3a–c. We have found that introduction of electron-withdrawing substituents into the

• . Investigation of the stepwise mechanism’s pathway allowed locating the only transition state (1a_1−7), which is appropriate to the addition of nitrile oxide 2a onto the double bond of enamine 1a_1, and the respective product – oxime 7. However, the intermediate 7 was found to cyclize to isoxazoline 3a through

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• also use Lewis acids [7]. The resultant quinolin-2-one is then reduced using strong hydride reducing agents such as LiAlH4 [8]. Similar THQs have also been prepared by a reductive Beckmann rearrangement of an oxime using diisobutylaluminium hydride (DIBAL) [9]. In contrast to this variety, the

A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin

• Matthias Bender,
• Henrik Mouritsen and
• Jens Christoffers

Beilstein J. Org. Chem. 2016, 12, 912–917, doi:10.3762/bjoc.12.89

• transformed to the corresponding protected ribitylamine via the oxime, which was submitted to reduction with LiAlH4. Key advantage compared to previous syntheses is the utilization of a polyol-protective group which allowed the chromatographic purification of a key-intermediate product providing the target

• . For example, the preparation of amine 5 by reduction of the oxime and its conversion with chlorouracil 3 turned out to be impossible when following a literature protocol [19]. We therefore decided to develop a robust synthesis of a protected derivative of amine 5 which could follow standard

• herein our synthetic approach to compound FO (1), which finally turned out to reliably yield the final product with high purity. Results and Discussion Synthesis of aldehyde 9 We envisioned the reduction of an oxime to be the most convenient access to the doubly isopropylidene protected amine 10 [21][22

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• , the less active compound is the weak acid oxime derivative 20a. Then, the formation of the more nucleophilic aldoximate is favored with the pyridinium derivatives 20b–d, explaining their high activity. The moderate efficiency of ketoximes 20d and 20e, compared to that of the corresponding aldoximes

• detoxification by 20b was not as effective, suggesting a non-reactive position of the nucleophilic oxime to efficiently react with this toxic. Worek et al. also demonstrated the prophylaxis effect associated to 20b in the case of anesthetized guinea pigs poisoned with cyclosarin [78]. A dose of cyclosarin s.c

• degradation of tabun (Scheme 4) [80]. However, it should be pointed out that a simple glucose derivative bearing the same nucleophilic group has a similar activity. The efficiency of 20c is therefore clearly related to the pyridinium oxime functional group and not to the inclusion properties of the

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• chloride/anhydrides [6][7][8][9][10][11], nitrile hydrolysis [12][13][14][15][16], Goldberg C–N cross coupling reaction [17], aldehyde/ketone amidation [18][19][20][21][22][23], the transamidation [24][25][26][27][28][29], and oxime rearrangement [30][31][32][33], to name only a few. It is obvious that the

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• hydroxylamines, as well as N-alkenyl and N-arylnitrones [1][2][3][4][5]. We have discovered that when this transformation is performed with oxime and hydroxamic acid substrates, these reactive intermediates can be accessed and subsequently rearrange to a variety of challenging organic fragments and heterocyclic

• corresponding tri- and tetrasubstituted pyridines 9 (Scheme 2C). This use of α,β-unsaturated oxime reagents for the synthesis of pyridines is unique from transition metal-catalyzed C–H bond functionalization processes that require a regioselective migratory insertion. This route is appealing due to the

• modularity of the Chan–Lam coupling process, and proceeds through a pathway that is distinct from the Liebeskind copper-catalyzed C–N bond coupling and electrocyclization (Scheme 2). Results and Discussion A Chan–Lam coupling between chalcone oxime 6a and cyclohexenylboronic acid (7a) was initially tested

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• –O bond with radical initiators [7][8][9][10][11][12][13][14][15] (Scheme 1a) or using thermal [16][17][18][19][20] or photoreaction conditions [21][22][23][24][25][26][27] (Scheme 1b). An alternative route to iminyl radicals is the single-electron reduction of oxime derivatives mediated by the

• cyanation of Grignard reagents was also established using readily available pivalonitrile as a simple CN source. Generation of iminyl radicals from oxime derivatives. Oxidative generation of iminyl radicals from N–H ketimines. Copper-catalyzed aerobic reactions of in situ generated biaryl N–H ketimines

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• -affirmed as the best compromise. Reactions of aryloxyacetic acids functionalized with suitably sited alkene 24, aromatic or oxime ether acceptors, were carried out with P25 under standard conditions and also in sol–gel TiO2 coated NMR tubes (see Scheme 6). For styrenyl acids 24 control photolyses in the

• absence of TiO2 showed that E/Z isomerisation was significant (25, 52–79%). Rather complex product mixtures containing E and Z-isomers of unreacted alkene, as well as low yields of dihydrobenzofurans 26, were obtained from 24a–c. Poor results were obtained from acids with aromatic and oxime acceptor

• . For example, it was recently shown that acyloximes act as hole acceptors with homogeneous PRCs [86] so it is likely that these, and related oxime derivatives [87], will also function with semiconductor catalysts. Similarly, α-keto acids are readily available and are promising candidates for SCPC

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• -caprolactam from cyclohexanone oxime involving the BR. The activation energy for the BR is almost the same as that of the nucleophilic substitution at sp2 nitrogen. To synthesize various aza-arenes and cyclic imines, such as quinolines, aza-spiro compounds and dihydropyrroles, the intramolecular SN2-type

• reaction at the oxime nitrogen is useful [1][2][3][4][5][6]. Here, we plan to use the BR in combination with a ring-rearrangement metathesis (RRM) [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] to generate lactam derivative 1. The RRM protocol involves a tandem process with several

• , respectively (Scheme 5). When the oxime 11a was treated with TsCl in the presence of NaOH in dioxane/H2O (3:4 v/v) at rt lactam 12 was formed in 34% yield. However, the oxime 11b did not give the rearranged product under the same reaction conditions, which clearly indicates that the oxime 11b is unreactive

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• facile route for the synthesis of novel macrolide spiroketals. Experimental Materials Oxime 1 was synthesized according to the previously published procedure [39][51][64]. The structures of all compounds were confirmed by NMR spectroscopy, LC–HRMS and molecular modelling. Both NMR spectroscopy and LC-MS

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• −0.95 V vs SCE. The results indicate: an increased acidity favours the formation of oxime 5 (Table 1, Nr. 1), whilst without a proton donor the olefin presumably is polymerized to a large extent (Table 1, Nr. 2). The addition of acetic acid in portions appears to be a good choice as a too high proton

• addition, however, could also favour the reduction of the nitro group to the oxime, which consumes four electrons. Decreasing hydrodimer yields with increasing temperature could be due to the existence of chemical side reactions of the radical anion, such as oligomerization or protonation, which are more

• derivative 14 deviates from this behaviour. Applying the usual electrolysis conditions no dimer 26 but only the oxime 24 (37%) and the nitro alcohol 25 (31%) are formed (Scheme 5a). As already indicated in the CV of 14 the dimerization of the intermediate radical anion of 14 is apparently hindered for steric

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• (CuAAC) and oxime ligation. This method was applied to the conjugation of biotin and β-linked galactose residues to yield an enzymatically active thermophilic lipase, which revealed specific binding to Erythrina cristagalli lectin by SPR binding studies. Keywords: chemoselectivity; dual protein

• cysteine has some drawbacks including the high tendency for disulfide bond formation or cross reaction with other cysteine residues, reaction reversibility, and occasionally side-reactions with basic side chains, e.g., lysines [33]. Specifically, in the current paper we use in the current paper the oxime

• conjugated with biotin using oxime ligation, by which the protein scaffold was immobilized on a streptavidin gold chip to monitor carbohydrate–protein binding studies by surface plasmon resonance (SPR). This immobilization strategy allowed easy handling and reproducible orientation, which are notable

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• the configuration at position 4 resulting in a complex diastereomeric mixture. Alternatively, reduction of menthone oxime can be achieved, either employing Bouveault–Blanc conditions [41], or via hydrogenolysis at a transition metal catalyst [42]. Both approaches lead to the desired product as a

• by enantiomeric resolution employing tartaric acid (see Scheme 2, pathway IV) [43]. By the amount of water in the crystallisation mixture the precipitation of the desired diastereomeric salt can be chosen [44]. Furthermore, we developed a Bouveault–Blanc-type protocol where (−)-menthone oxime is

• converted to 3 in attractive diastereoselectivity (see Scheme 2, pathway II) [45]. However, the necessity for excess amounts of sodium metal constitutes a major drawback. Consequently, we also investigated on electrochemical alternatives for the reduction of (−)-menthone oxime. In this context, we found

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• (amide, heteroaromatic, oxime, and so on) and compounds with activated C–H bonds (aldehydes, alcohols, ketones, ethers, amines, amides, compounds containing the benzyl, allyl, or propargyl moiety). An analysis of the published data showed that the principles at the basis of a particular cross

• functional groups (amide, heteroaromatic, oxime, and so on) and compounds with activated C–H bonds (aldehydes, alcohols, ketones, ethers, amines, amides, compounds containing a benzyl, allyl, or propargyl moiety). An analysis of the published data showed that the principles at the basis of a particular cross

• -containing moieties (amide, pyridine, oxime, etc.) are most commonly used as directing groups, which are responsible for the regioselectivity of the C–O coupling. Most transformations of this type are catalyzed by Pd(II) compounds. Examples of the use of copper and ruthenium compounds as catalysts were also

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• yields (up to 95%, Scheme 4). McBurney et al. prepared various N-heterocycles, using oxime carbonates as excellent precursors for the photoinduced generation of iminyl radicals, whereby at standard photolysis conditions, 3-substituted 6-methylphenanthridines were obtained in good to quantitative yields

• -halobenzyl)arylamines, oxime carbonates, isocyanobiphenyls, etc.). Phenanthridines are usually obtained within 2–3 reaction steps, by application of different radical initiators. An intriguing alternative is the radical generation by UV irradiation with or even without a photocatalyst. The major advantage of

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• including azide–alkyne cycloadditions [9][10], Diels–Alder reactions [11][12], maleimide–thiol reactions [13], thiol–ene additions [14], and imine/oxime conjugations [15]. In this article we demonstrate that dihalocarbenes can be used to generate dihalocyclopropanes on olefin terminated SAMs. We recently

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• formation of a C,O-bond and generation of the five-membered heterocycle. Hydroxy, carboxy and oxime moieties were tested as nucleophiles for this reaction, leading to the corresponding tetrahydrofurans, γ-lactones and isoxazolines, respectively. The chemistry depicted in Scheme 13 was also used for the

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• ). v) Reduction of the environmental toxicity The CDs can be used to minimize environmental pollution. As an example, in 1994, Loukas et al. reported the effect of γ-CD on dicyclopropylmethanone O-(diethoxyphosphoryl)oxime (named DCPE), a very active insecticide (Figure 4) [58]. The complexation of

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• carbonyl groups can be exploited for carbohydrate functionalization [15][16] by reductive amination, oxime or hydrazone formation to yield suitably functionalized saccharides (Figure 1). Given the relevance of L-fucose in mammal oligosaccharides, α-L-(2-aminoethyl) fucoside [17] and α-O-L

• of the glycoconjugation to the G0 dendron and G1 dendron by reductive amination, we decided to evaluate the possibility to obtain better conjugation yields by oxime ligation. Thus, G0, G1 and G2 dendrons 1–3 were reacted with α-O-L-fucopyranosyloxyamine (5) in citrate buffer at pH 3.5 [20] (Scheme 4

• quantitative yields. Conclusion In conclusion, novel G0, G1 and G2 dendrons suitable for glycoconjugation by carbonyl chemistry were synthesized. The conjugation of the saccharide by reductive amination was characterized by a low efficiency. On the other hand, the oxime ligation afforded the glycoconjugated

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• alkyne–azide cycloaddition (CuAAC) [18] or SN2 reaction [19]. In addition, orthogonal chemoselective ligations were proved more attractive strategies to prepare hGCs in high yields, in part because they require less synthetic and purification steps. For example, oxime and CuAAC ligations have been used

• (Scheme 1). Such derivatives have proved to be useful in bioconjugates chemistry [25] and for the preparation of thioether-linked tetravalent glycocyclopeptides which have shown highest inhibition against a model lectin in comparison with analogues bearing oxime and triazole linkage [26]. Glycosyl thiols

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• , instead of hydrazide-PEGs, generated a more stable oxime linkage with the carbohydrate aldehydes. Similar to the other gonadotropins, TSH is a glycosylated protein, and the role of the N-linked oligosaccharides is well established. The effect of PEG size and mono- vs multi-PEGylation was compared both in