Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• identified by X-ray diffraction (Figure 3, left, see Supporting Information File 2). It is known that anisole can be ortho-deprotonated using the lithium–zinc base in THF [35]. It was thus of interest to involve N-(4-methoxyphenyl)-substituted azole substrates in the deprotonation–iodination sequence. Under

• procedure 3 for the deprotonative metallation followed by iodination (analogous to that described in [60]). To a stirred, cooled (0 °C) solution of 2,2,6,6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2–3 mL) were successively added BuLi (about 1.6 M hexanes solution, 1.5 mmol) and, 5 min later, ZnCl2

• 4 for the deprotonative metallation followed by iodination (analogous to that described in [60]). To a stirred, cooled (0 °C) solution of 2,2,6,6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2-3 mL) were successively added BuLi (about 1.6 M hexanes solution, 1.5 mmol) and, 5 min later, ZnCl2

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• at the 3 position to give 126 (66%) and later, N-allylation was carried out to afford the diallylindole 127 (69%, Scheme 18). A three-step (123→124→125→127) sequence was found to give a higher yield of the 1,3-diallylindole (127). Iodination of 123 gave the 3-iodoindole (124) quantitatively, which on

Self-assembly of heteroleptic dinuclear metallosupramolecular kites from multivalent ligands via social self-sorting

• Christian Benkhäuser and
• Arne Lützen

Beilstein J. Org. Chem. 2015, 11, 693–700, doi:10.3762/bjoc.11.79

• commercially available 2-aminopyridine (4) (Scheme 4) following mostly literature-known protocols. The electrophilic iodination of aminopyridine 4 gave iodide 5 in good yield. Compound 5 was then subjected to a Sandmeyer-like chlorination to 6 which in turn was transformed in a Sonogashira reaction with

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• ethynyl tetra(ethylene glycol)methyl groups [58][59]. Synthesis of the BODIPY precursors The synthesis of the tris-iodo functionalized BODIPY dyes and their acetylenic derivatives is sketched in Scheme 1. The synthesis of derivatives 7 and 8 have previously been reported using a regioselective iodination

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• –Jones nucleosidation using silylated thymine and TBAF [42][43][44], was converted into the corresponding iodo-derivative 10 by sequential tosylation and iodination. The subsequent reaction of 10 with sodium azide, performed at 50 °C in CH3CN/H2O (1:10) in the presence of NH4Cl for 48 h afforded two

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• alcohol functionality takes place. It is mentionable that under the reaction conditions no aromatic iodination could be observed. Next to sodium iodide other iodide sources such as KI, I2 or Bu4NI can be used, whereas applying other halogenides such as NaBr, Et4NBr or Bu4NCl led to a complex mixture of

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

• commonly employed in the oxidative coupling of OH-reagents with carbonyl compounds. Methods were developed for the sulfonyloxylation of ketones, in which iodoarene is generated in situ by the iodination of arene with molecular iodine [183] or NH4I [184] in the presence of m-chloroperbenzoic acid. In the

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

• azido groups The introduction of the azido groups into the β-CD-polymer has been performed by adapting the sequence iodination → azidation [19] to the specific structure. The target was to introduce one azido moiety per CD ring in 0.5–2% of the CD population. The optimization of the three-step reaction

• the same reasons the work-up and the purification steps had to be carefully planned without relying on chromatographic techniques. Taken into consideration that the azidation step is an exhaustive process (if NaN3 is used in excess), the real challenge was to control the degree of the iodination. In

• ) modifying the monomer prior to branching. The strategies were demonstrated on several examples using various fluorescent moieties for labeling. For the first strategy, the fluorophore is attached on the primary side of the CD scaffold, if the sequence iodination→azidation is used. If the intermediate

Scalable synthesis of 5,11-diethynylated indeno[1,2-b]fluorene-6,12-diones and exploration of their solid state packing

• Bradley D. Rose,
• Peter J. Santa Maria,
• Aaron G. Fix,
• Chris L. Vonnegut,
• Lev N. Zakharov,
• Sean R. Parkin and
• Michael M. Haley

Beilstein J. Org. Chem. 2014, 10, 2122–2130, doi:10.3762/bjoc.10.219

• as the more robust bromines in 11, yet avoid annulene transannular synthesis [24]. Instead, the route we chose involved key precursor 12, which surprisingly is an unknown compound. Starting with commercially available 2,5-dibromo-p-xylene (13) (Scheme 2), iodination using the method reported by

Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

• Simon Rondeau-Gagné,
• Jules Roméo Néabo,
• Maxime Daigle,
• Katy Cantin and
• Jean-François Morin

Beilstein J. Org. Chem. 2014, 10, 1613–1619, doi:10.3762/bjoc.10.167

• this study as a control molecule because of the absence of 2-hydroxyethoxy chains in its structure, providing a reliable comparison. Results and Discussion The synthetic pathway toward PAM2 and PAM3 is shown in Scheme 1. Starting from commercially available 4-hydroxybenzoic acid, iodination was

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• explored to produce the corresponding functional monomer 4 and thus the β-CD dimer 5. Linker 2 was prepared from methyl 2-aminoterephthalate via a sequence of diazotization–iodination–phosphanylation reactions [4] (Scheme 2a). The new, doubly phosphanylated dimethyl terephthalate linker 3 was prepared from

• p-xylene via consequtive iodination–oxidation–esterification reactions [32][33][34], followed by the final phosphanylation step that afforded linker 3 in excellent yield (Scheme 2b). Compounds 2 and 3 each displayed one signal in the 31P NMR spectrum at −3.5 and −3.8 ppm (Supporting Information File

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• . Tour [30], M. Gomberg [31], and V. Prelog [32][33] leading to (rac)-2,2’-dihydroxy-9,9’-spirobifluorene ((rac)-1) in six consecutive steps. This sequence involved a Sandmeyer-like iodination, followed by a Grignard reaction with fluorenone to furnish the corresponding tertiary alcohol. This alcohol was

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

• synthesis of diastereomers of dioxanes 252a,b containing triple bonds. Hydroperoxides 251a,b that were synthesized by the ozonolysis of 250 were treated with potassium tert-butoxide. One of the diastereomers, 252a, was then modified first via the stereoselective hydrozirconation and iodination to 253a and

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• . Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial reduction and ester hydrolysis then gave resolvin D2 (1). Keywords: catalysis; eicosanoid; natural product

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

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• times, 15 mL), dried over Na2SO4, filtered and evaporated to afford the corresponding crude mixture which, in most cases, was pure enough to use in the next step without further purification. Iodination of terminal alkynes The starting alkyne (1 equiv; 2 mmol) was dissolved in acetone (10 mL). Then

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• followed by HI elimination using immobilized DBU as fixed bed material (Scheme 2) [9][22][23]. All vinyl azides used in this report were prepared by azido-iodination of the corresponding alkenes followed by DBU-mediated HI elimination (for details see the Supporting Information File 1). Results and

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• would ultimately be formed by a Myers alkylation [23] of (+)-pseudoephedrine derived amide 7 with allylic iodide 8. The initial epoxidation substrate of type 6 that we targeted possessed benzyl and TBDPS ethers as the protecting groups. First, allylic iodide 8 was synthesized by iodination of the

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• iodide 26 was generated by hydrozirconation/iodination of the free alkyne with Schwartz’s reagent [47]. The vinyl nucleophile 27 could be generated by Knochel’s Mg/I exchange [48] and employed successfully in the three-component-coupling reaction with silyl glyoxylate 1a and aldehyde 16ba to assemble 28

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• group (in place of the TBS of the original synthesis) onto the PEG moiety to facilitate the early stages of the synthesis by providing a UV-active chromophore for easy detection; (b) introduction of a high yielding two-step iodination process, which avoids chromatography; and (c) reversing the sequence

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT₂ receptor family

• Adam Pigott,
• Stewart Frescas,
• John D. McCorvy,
• Xi-Ping Huang,
• Bryan L. Roth and
• David E. Nichols

Beilstein J. Org. Chem. 2012, 8, 1705–1709, doi:10.3762/bjoc.8.194

• of a BOC protecting group (Scheme 2). Thus, we first prepared 2-(2,5-dimethoxyphenyl)cyclopropanecarboxylic acid methyl ester (7) from the corresponding cinnamic ester 6 [5], followed by I2/AgNO3 iodination (Scheme 1), and base hydrolysis of the resulting ester to provide iodo acid 10a. Hydrolysis of

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• -diol. The substrate for the aldol key step 8 could be prepared starting with commercially available 2,4-dihydroxybenzaldehyde (9) by a selective iodination of the 5-position of the aromatic ring, protection of the hydroxy group in the 4-position, and 2-O-acetonylation of the selectively protected

• salicylaldehyde (Scheme 6). The total synthesis of smyrindiol is depicted in Scheme 7. Firstly, the O-acetonyl-salicylaldehyde 13, as the substrate for the aldol reaction, was synthesized in five steps. Iodination of commercially available 2,4-dihydroxybenzaldehyde (9) with iodine monochloride in acetic acid [11

• ] furnished a mixture of different iodination products. After the addition of water to the reaction mixture, only the 5-iodo derivative 10 precipitated from the solution and could be separated from the other isomers by filtration in 56% yield. We decided to protect the 4-hydroxy group as an allyl ether, as we

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• preparation of internal alkynes [24]. We started our investigations with the persilylated 1-iodoglucal 7, which is easily available by a sequence of lithiation and iodination from the parent, fully TIPS-protected congener [25]. The Sonogashira reaction was carried out under standard conditions. Pd(PPh3)2Cl2

Synthesis of oleophilic electron-rich phenylhydrazines

• Aleksandra Jankowiak and
• Piotr Kaszyński

Beilstein J. Org. Chem. 2012, 8, 275–282, doi:10.3762/bjoc.8.29

• attempted monoiodination of 8 with BTMA·ICl2 by using a general literature method [35] gave only traces of the product and nearly all of the starting material was recovered. Iodination under the Kern conditions [36][37] (HIO3/I2) gave a mixture of mono- and diiodo derivatives, which were difficult to

Synthesis and oxidation of some azole-containing thioethers

• Andrei S. Potapov,
• Nina P. Chernova,
• Vladimir D. Ogorodnikov,
• Tatiana V. Petrenko and
• Andrei I. Khlebnikov

Beilstein J. Org. Chem. 2011, 7, 1526–1532, doi:10.3762/bjoc.7.179

• unreactive compound 5. The reactivity of pyrazole-containing thioether 3 in aromatic electrophilic substitution was evaluated by using nitration and iodination reactions as examples. Nitration of compound 3, by 68% nitric acid in concentrated sulfuric acid, results in both substitution in the heterocyclic

• rings and sulfur atom oxidation to sulfoxide (Scheme 4). Previously, we found that the oxidative iodination of different bis(pyrazole) compounds proceeds smoothly when using an I2/HIO3 system [18]. The action of this system on thioethers 3 and 4 resulted in incomplete iodine consumption and a complex

• product mixture, which contained, according to NMR, both mono- and disubstituted iododerivatives of the corresponding sulfoxides together with the starting material. Obviously, the presence of a reductive sulfur atom in the substrate deactivates the iodinating system, and therefore oxidative iodination is