Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• oxygen is possible. A stereoselective electrochemical method of the chlorination of steroidal Δ5-olefins was described by Takayama et al. [38]. The oxidation of cholesterol was carried out in an undivided cell under constant current conditions in CH2Cl2/MeCN/H2O (2:2:1), the cathode and anode being

• chlorination of some Δ5-steroids (Scheme 5) was reported by Milisavljević and Vukićević [40]. The electrolyses were carried out in dichloromethane under galvanostatic conditions with a graphite anode in an undivided cell. The supporting electrolyte tetraethylamonium chloride was a source of chloride ions

• the Gif system. Electrochemical oxidation of cholesteryl acetate (1a) with dioxygen and iron–picolinate complexes. Electrochemical chlorination of cholesterol catalyzed by FeCl3. Electrochemical chlorination of Δ5-steroids. Electrochemical bromination of Δ5-steroids in different solvents. Direct

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

A facile synthesis of functionalized 7,8-diaza[5]helicenes through an oxidative ring-closure of 1,1’-binaphthalene-2,2’-diamines (BINAMs)

• Youhei Takeda,
• Masato Okazaki,
• Yoshiaki Maruoka and
• Satoshi Minakata

Beilstein J. Org. Chem. 2015, 11, 9–15, doi:10.3762/bjoc.11.2

• due to background side-reactions such as chlorination on the aromatic rings and oxidative oligomerization of BINAMs. Furthermore, this new oxidative method was found to be applicable in the ring-closing reaction of 1,1’-biphenyl-2,2’-diamine (3) leading to benzo[c]cinnoline (4) in a good yield

• , although the modification of the reaction temperature was required (Scheme 4, for the detailed modification study of reaction conditions, see Supporting Information File 1). A possible reaction pathway of the oxidative ring-closure of 1a leading to 2a is illustrated in Scheme 5. Chlorination of an amino

• group of 1a with t-BuOCl would generate N-monochlorinated BINAM (Int-A) and release t-BuOH. The N-chlorination would induce umpolung reactivity of the amino moiety because of the attachment of electronegative halogen species on the N atom [27][28][29][30], and thereby an intramolecular nucleophilic unit

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• modified β-CD was then copolymerized with epichlorohydrin in a ratio that resulted in the formation of a water-soluble copolymer. The azo dye modified β-CD epichlorohydrin copolymer was used as a molecular fluorescent sensor for the detection of chloroform, one of the chlorination byproducts in water. Here

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• . Oxidation of chloride, which itself originates in the CCl4 reactant, likely results in partial chlorination of the acetonitrile solvent, releasing protons which in turn cause the formation of chloroform by attacking the cathodically formed carbanions [143]. An undivided electrosynthesis setup with stable

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• dichlorides can be obtained either from chlorination of phosphonic acids [65][66] or from treatment of an allyl chloride such as 61 with phosphorus trichloride followed by hydrolysis to give 62 [15][67]. Reactions of unsymmetrical amines or aminoalcohols such as ephedrine with phosphonic acid dichlorides

• ) followed by chlorination gave chlorodiketone 147. The latter was then treated with sodium carbonate in boiling xylene to afford cyclopentenone 148, presumably via decarbonylation of a cyclopropanone intermediate. Addition of the lithium anion of chiral phosphonamide 64a at low temperature produced adduct

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• reactions discussed above, some of these reactions did not proceed to completion, even when the reaction time was lengthened. Generally, it was observed that the bromination reactions afforded higher product yields than did the corresponding chlorination reactions (Table 2, entries 1–8), except when

• , and realizing that it was returned as the byproduct of the above reactions, we next examined its recyclability in the chlorination of alcohol 4H and aziridine 8B. The results of these studies are shown in Table 4 and Table 5, respectively. In these experiments, the polymer recovered by filtration of

• . Synthesis and applications of rasta resins 16 and 17a,b. Synthesis of bifuncitonal rasta resin 18. Appel reactions using 16.a Halogenation reactions of aldehydes using 16.a Halogenation reactions of aziridines using 16.a Recycling of 16 in the chlorination of 4H.a Recycling of 16 in the chlorination of 8B.a

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• ]pyrimidine 7. Direct chlorination of 1 in a moderate scale (1 g) using POCl3 proved to be very low yielding [28]. It remains unclear if this was due to the poor solubility of PreQ0 or to the presence of unprotected amino functionalities. In order to overcome this issue, the exocyclic amine was protected [14

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• chlorination such as the use of N-chlorosuccinimide or, as reported more recently, CuCl2 produced, in the latter case, 7-6 with full stereocontrol (Scheme 7-iii) as unambiguously determined by X-ray diffraction analysis [31]. The addition of nucleophilic species (amine, alcohol, alkyllithium, etc.) on 7-6 or

• with full stereocontrol. This result indicates that both steps (i.e., the chlorination and subsequently the substitution of the chlorine atom with the nucleophile) were stereocontrolled. The detailed mechanism of each step, which may involve penta-coordinated phosphorus intermediates [28], is not well

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• hexacyanoferrate then afforded diamide 24 in moderate yield [38]. Its subsequent chlorination with a mixture of phosphorous pentachloride and phosphoryl chloride furnished dichloride 25 in quantitative yield [38]. Finally, two-fold Suzuki cross-coupling of 25 with 2,6-dimethoxyphenylboronic acid (26) derived from

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• the treatment of multiple myeloma and mantle cell lymphoma [21]. This product is usually synthesized in three representative processes: (1) to use (1S,2S,3R,5S)-(+)-2,3-pinanediol as the chiral auxiliary for the addition reaction followed by chlorination and amination [14][15]; (2) to perform copper

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• catalysis; chlorination; fluorination; organocatalyst; organo-fluorine; Introduction Fluorinated organic molecules are of considerable interest in pharmaceutical and agricultural chemistry owing to the unique properties of the fluorine atom [1][2]. These compounds, especially with one or more fluorinated

• α-chloro-α-fluoro-β-keto esters via the sequential chlorination–fluorination of β-keto esters with the Cu(II) complex of SPYMOX [9], a spiro chiral oxazoline ligand developed by our research group [9][10][11][12]. In that study, we succeeded in determining the absolute stereochemistry of the α

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• diazonium salt followed by a Sandmeyer reaction resulted in 4b (61% over two steps). The isomer 4c was efficiently prepared by double methylation of 2-chlororesorcinol (8) with potassium carbonate and methyl iodide in acetone (88%), while 4f was obtained by chlorination of dimethoxybenzene 9 with

• followed by methylation yielded 48% of 10k. Chlorination of veratrole (5) with two equivalents of benzyltrimethylammonium tetrachloroiodate resulted in 10d (45%), while the same procedure starting from 1,4-dimethoxybenzene gave access to 10j (38%). The NMR spectroscopic data and results of GC–MS analyses

• dichlorodimethoxybenzene (10b or 10k) can arise by a second chlorination from the monochlorodimethoxybenzene (4b or 4f, respectively), suggesting that in both organisms the sets of chlorinated compounds arise via one and the same biosynthetic pathway. Known structurally related compounds from fungi are drosophilin A (19

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• .9.302 Abstract The synthesis of 5,6- and 7,8-diaminoquinoline derivatives starting from angularly annelated selenadiazoloquinolones is presented. Simple chlorination of the pyridone ring followed by reductive deselenation of the 1,2,5-selenadiazole ring afforded novel 4-chloro-o-diaminoquinolines

• . Dechlorination of 4-chloro-7,8-diaminoquinoline gave 7,8-diaminoquinoline hydrochloride which was successfully employed as starting material in the synthesis of condensed nitrogen heterocycles. Keywords: chlorination; deselenation; nitrogen heterocycles; o-diaminoquinolines; selenadiazoloquinolones

• -benzoselenadiazole skeleton while the pyridine ring can be obtained by transformation of the pyridone core [15]. The synthesis of 7,8-diaminoquinoline (3) starting from selenadiazolo[3,4-h]quinolone 1 is depicted in Scheme 1. In the first step, the aromatization of the pyridone ring by chlorination with POCl3 in DMF

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

• readily prepared by chlorination of 2-pyridone (1.42) with phosphorous oxychloride (Scheme 8) [31][32]. The resulting primary alcohol 1.45 is then subjected to a second SNAr reaction with 4-fluorobenzaldehyde [33]. A Knoevenagel condensation of the aldehyde functionality in compound 1.47 with

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• ] (Scheme 4). This protection step was carried out in order to avoid dehydrogenation or chlorination of the secondary amine in the subsequent oxidation steps [64][65]. Acetal cleavage under mild protic conditions furnished the hydroxycarbamate, which underwent two-step oxidation with Dess–Martin periodinane

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• 1a as the substrate, which was efficiently prepared on gram scale from the corresponding benzaldehyde via oxime formation and subsequent NCS-mediated chlorination [53]. Screening different solvents (MeCN, acetone, EtOAc, MeOH and iPrOH) and immobilised thiourea species (QP-TU [54] and QS-MTU [55

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• chlorination using hydroperoxides as the O-radical source, in which the C-radicals generated by the 1,5-H radical shift were chlorinated (Scheme 2a) [14]. If reductive generation of the O-radicals from hydroperoxides could be achieved under an O2 atmosphere, the C-radicals generated by 1,5-H radical shift

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• 4-ethoxybenzaldehyde was condensed with diacetyl monoxime under acidic conditions. The resulting oxazole N-oxide 9 was converted to the chloromethyloxazole 10 via selective chlorination with phosphorous oxychloride in good yield. Addition of thioglycolic acid led to the carboxylic acid 11, which was

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• %, respectively). Sulfur monochloride is known as a powerful chlorinating agent for chlorination of aromatic and heteroaromatic compounds [14][15]. In an attempt to increase the sulfurating ability of S2Cl2 the complex 8 obtained from S2Cl2 and 2 equiv of DABCO [16] was used. We have recently shown that this

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• biomacromolecules at high concentrations of strong acids, a polystyrene resin was chosen that contains a tritylchloride linker. The resin was obtained by treatment of Merrifield resin with p-hydroxytriphenylmethyl alcohol and subsequent chlorination [49][50]. This tritylchloride linker allowed a mild cleavage of

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• pyridine 16, which was isolated in 61% yield. Further deprotection of the primary alcohol with TBAF followed by chlorination with thionyl chloride finally gave the desired chloromethylpyridine 17, an intermediate used for the preparation of sarizotan 19 at Merck KGaA by coupling of this pyridine fragment

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• chlorination of cyclohexane (72) with sulfuryl chloride under 15 W black-light irradiation (Scheme 23); however, the reaction was relatively inefficient and productivity was low (0.18 mmol/h) [75]. A biphasic photocyanation of pyrene (74, Scheme 24) was shown to be efficient in a polymer microchannel reactor

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• reported the use of a mutant of A. pretiosum blocked in Asm12 (chlorination) and Asm21 (carbamoylation) and therefore producing proansamitocin (2) in good yield (up to 106 mg/L of fermentation broth) [17]. Additionally, we isolated small amounts of O-methyl proansamitocin 7 (2.3 mg/L), 10-epi

• (Scheme 1). While examining the fermentation extract for byproducts we were able to identify two new metabolites, 15 and 16. Formation of compound 15 can be traced back to inefficient chlorination, a phenomenon that we have encountered before in other feeding experiments with proansamitocin [25]. More

• File 1). Fermentation products, proansamitocin (2) and derivatives 7–9, of the Asm12 and Asm21-blocked (chlorination, carbamoylation) mutant strain A. pretiosum Δasm12/21 (yields given as isolated product per volume of fermentation broth) [17]. Summary of ansamitocin biosynthesis and structure of the

Regioselective chlorination and bromination of unprotected anilines under mild conditions using copper halides in ionic liquids

• Han Wang,
• Kun Wen,
• Nurbiya Nurahmat,
• Yan Shao,
• He Zhang,
• Chao Wei,
• Ya Li,
• Yongjia Shen and
• Zhihua Sun

Beilstein J. Org. Chem. 2012, 8, 744–748, doi:10.3762/bjoc.8.84

• Science, Shanghai, 201620, China 10.3762/bjoc.8.84 Abstract By using ionic liquids as solvents, the chlorination or bromination of unprotected anilines at the para-position can be achieved in high yields with copper halides under mild conditions, without the need for potentially hazardous operations such

• as supplementing oxygen or gaseous HCl. Keywords: halogenation; ionic liquids; oxydation; regioselectivity; solvent effects; Introduction Chlorination and bromination of aromatic rings are classical and widely performed transformations, which are useful in many multistep organic-synthesis

• procedures. Regioselectivity with electron-rich substrates such as aniline will predominantly produce para- and ortho-substitutions. However, chlorination or bromination of aniline derivatives is often performed with protected anilines. This increases both the cost of synthesis and the environmental impact