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

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• acid yielding isosorbide diacrylate (9a) and isosorbide dicrotonate (9b), which were reacted with benzaldehyde oxime in the presence of zinc(II) iodide and boron triflouride etherate as catalysts to obtain N-alkylated dinitrones 10a/b. Poly(isosorbide itaconite -co- succinate) 13 as a bio-based

• ) thereby hinting at the formation of nitrones. In contrast to previous reports [12], we lowered the catalyst amount of ZnI2/BF3∙OEt2 to reduce several side reactions. For example, it could be determined, that high amounts of catalyst led to the oxidation of the oxime to benzaldehyde or the cleavage of

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• virtually complete diastereoselectivities. Results and Discussion Preparation of the N-phosphinyl-protected α-imino esters After screening the classical procedures for the synthesis of α-imino esters [3][55][56], we initially tried an approach with chlorophosphine and ester oxime as starting materials

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• led to nearly quantitative hydrolysis of the dioxolane affording diol oxime 20 as 95:5 mixture of E- and Z-isomers. However, if solid NaOH was added to the reaction mixture and heated for several hours, the dioxolane survived, affording a 1:1 mixture of E/Z-oximes, which were tosylated after short

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• been reported by numerous authors. Among them, Zhao et al. [18] studied the coupling of non-activated aryl iodides with different alkenes using Pd-MCM-41-NH2. Other examples include Pd-FSM 16 (functionalised with pyridine-carboimine or quinoline-carboimine) [19], oxime carbapalladacycle anchored on

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• the trifluoroacetaldehyde oxime 2 was developed. In a previous work [25], 2 was obtained as an etherate complex from the reaction between 2,2,2-trifluoroethane-1,1-diol (TFAL) and hydroxylamine hydrochloride. In our work, reaction of TFAL and an aqueous solution of hydroxylamine (50 wt %) yielded the

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• flow conditions and illustrates that this first step has a throughput more than 63-fold higher than the batch Tiffeneau–Demjanov conditions. The concentrated Tiffeneau–Demjanov reaction not only increased the throughput but also enabled oxime formation without the removal of water. Using excess

• hydroxylamine hydrochloride (4 equiv) in methanol resulted in full conversion to compound 2. At a total flow rate of 5 mL/min at 60 °C using a 20 mL reactor (4 minutes residence time), we achieved a throughput of 177 mg/min (24-fold improvement relative to batch). The hydrogenolysis of the oxime illustrates a

• flow chemistry challenge. The output from the oxime step contains excess hydroxylamine and salts carried from the first step that poisoned the packed-bed catalyst we screened. In theory, continuous purification could remove these materials but existing strategies do not enable removal of water soluble

AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldoximes with α,β-unsaturated carbonyl compounds

• Qiuping Ding,
• Dan Wang,
• Puying Luo,
• Meiling Liu,
• Shouzhi Pu and
• Liyun Zhou

Beilstein J. Org. Chem. 2013, 9, 1949–1956, doi:10.3762/bjoc.9.231

• that this one-pot process was highly efficient to construct 1-alkylated isoquinolines under very mild conditions. With the optimized conditions in hand, the scope of the procedure was investigated for the reaction of 2-(p-tolylethynyl)benzaldehyde oxime (1b) with a series of α,β-unsaturated carbonyl

• products 3 in moderate to good yields. For instance, reaction of 2-((4-methoxyphenyl)ethynyl)benzaldehyde oxime (1c) with methyl methacrylate (2a) under the conditions described above gave the desired product 3j in 75% yield (Table 2, entry 1). A better yield was obtained when substrate 1e was employed in

• the reaction (83% yield, Table 2, entry 3). The usage of 2-(cyclopropylethynyl)benzaldehyde oxime (1f) in the reaction led to a similar yield (80% yield, Table 2, entry 5). However, low yields were obtained when 2-(hex-1-yn-1-yl)benzaldehyde oxime (1g) reacted with methyl methacrylate (2a). In the

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor

• Rajesh Munirathinam,
• Roberto Ricciardi,
• Richard J. M. Egberink,
• Jurriaan Huskens,
• Michael Holtkamp,
• Herbert Wormeester,
• Uwe Karst and
• Willem Verboom

Beilstein J. Org. Chem. 2013, 9, 1698–1704, doi:10.3762/bjoc.9.194

• X-ray photoelectron spectroscopy (XPS). XPS revealed the presence of one gallium per 2–3 styrene sulfonate groups of the polymer brushes. The catalytic activity of the Lewis acid-functionalized brushes in a microreactor was demonstrated for the dehydration of oximes, using cinnamaldehyde oxime as a

• Strecker reaction by Wiles and Watts [13]. The dehydration of cinnamaldehyde oxime [18] was used as a model reaction to study the catalytic activity of a microreactor with gallium immobilized onto its channel walls (Scheme 1). Results and Discussion The catalytic polymer brush layer was first developed on

• with gallium on the microchannel interior in the continuous flow-mode. The dehydration of cinnamaldehyde oxime (1, 25 µM in acetonitrile) was used as a model reaction to study the catalytic activity of the gallium-functionalized microreactor, at 90 °C and 5 atm pressure, generated using a back pressure