The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• –Gilbert homologation [128][129] under Bestmann–Ohira conditions [130][131], a Schwartz hydrozirconation/iodination sequence [132], and appropriate protecting group manipulations. Vinyl iodide 21, which comprises the C8–C13 segment was prepared from TBDPS-protected (R)-hydroxy-2-methylbut-3-ene 20 that was

• obtained according to literature procedures [133], thus setting the stereochemistry at C12. The five-step sequence from 20 to vinyl iodide 21 included a (poorly diastereoselective) epoxidation, epoxide opening with a propynyl anion and a hydrozirconation/iodination reaction to generate the vinyl iodide

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• compounds and their precursors from Table 1 are taken into consideration, some valuable structure–activity relationships appear. 13α-Estrone (1) displays 17β-HSD1 inhibitory potential similar to that of the natural substrate estrone. Iodination at C-2 of 1 improves the inhibitory potential, resulting in a

• submicromolar IC50 for compound 3. Phenylalkynylation of the 2-iodo compound 3 retains or further improves the inhibition, depending on the nature of the substituent at C-4”. Concerning the 4-regioisomers, iodination leads to an efficiency similar to that of compound 1, whereas the inhibition is lost following

• C–C coupling. 13α-Estrone 3-methyl ether 2 possesses a weaker inhibitory effect than the 3-hydroxy compound 1. Iodination or phenylalkynylation at C-2 diminishes inhibition of 2. Introducing iodine onto C-4 of compound 2 leads to a 10-fold decrease in its IC50 value. 4-Phenylalkynyl derivatives 10

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• iodide 17 after O-acylation, iodination of the terminal alkyne and finally diimide-mediated syn-reduction [11]. Next, DDQ-mediated removal of the PMB protecting group yielded vinyl iodide 18. The synthesis of both fragments 13 and 18 set the stage for the Suzuki–Miyaura coupling which delivered the

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• as intermediates. The mechanism has not yet been clarified in detail. A probable catalytic cycle is proposed in Scheme 4 based on the above experimental results and previous literature reports. The process begins with the formation of α-iodoaryl ketones 5 and 6 via iodination of aryl ketones with I2

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd

• ]. Reaction of 1a and 1b with 2-hydrazinopyridine and phenylhydrazine, respectively, afforded the tri(hetero)arylpyrazoles 2a–d which were further converted into the corresponding 4-iodopyrazole derivatives 3a–d by treatment with I2/HIO3 in acetic acid at 80 °C (Scheme 2). The latter iodination method turned

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• organocatalysts with a bulky substituent at C2 were synthesized from chiral imines derived from (R)-glyceraldehyde acetonide by diastereoselective allylation followed by a sequential hydrozirconation/iodination reaction. The new compounds were found to be effective organocatalysts for the Michael addition of

• /iodination of chiral homoallylic amines has been described as a straightforward approach to enantiomerically pure 2-substituted pyrrolidines [13][14]. Therefore we decided to test this methodology to gain access to the pyrrolidine ring in compound C. The required chiral homoallylic amines B can be easily

• enantioselectivites from 72–84% ee. Conclusion In conclusion, we have prepared 2-substituted pyrrolidines using a hydrozirconation/iodination reaction of chiral homoallylic amines. The latter were obtained on a multigram scale from imines derived from glyceraldehyde. These easily available compounds are new tuneable

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• Michal Medvecky Igor Linder Luise Schefzig Hans-Ulrich Reissig Reinhold Zimmer Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, D-14195 Berlin, Germany 10.3762/bjoc.12.289 Abstract Iodination of carbohydrate-derived 3,6-dihydro-2H-1,2-oxazines of type 3 using iodine and

• . This was exemplarily demonstrated by the hydrogenation of syn-21 and anti-24 and by a click reaction of a 5-alkynyl-substituted precursor. Keywords: amino alcohol; click reaction; cross-coupling reactions; hydrogenation; iodination; 1,2-oxazines; Introduction Over the last decade, we have intensively

• focused our interest on the so far unknown functionalization at the C-5 position of the synthetically useful enantiopure 3,6-dihydro-1,2-oxazines 3. Herein, we now disclose our results on the iodination of 3 to provide the previously undescribed 5-iodo-1,2-oxazine derivatives 4. These new intermediates

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• the chloride has less affinity to the macrocycle. It was not possible to reproduce the literature method [14] for per-6-chloro-β-CD synthesis, but a protocol using p-toluenesulfonyl chloride under reaction conditions that were analogous to the iodination/bromination reaction resulted in the targeted

Synthesis and characterization of fluorinated azadipyrromethene complexes as acceptors for organic photovoltaics

• Forrest S. Etheridge,
• Roshan J. Fernando,
• Sandra Pejić,
• Matthias Zeller and
• Geneviève Sauvé

Beilstein J. Org. Chem. 2016, 12, 1925–1938, doi:10.3762/bjoc.12.182

• forward assuming complete conversion from the first reaction. To install phenylacetylene groups, iodination of the ADP derivatives was done according to literature procedures and purified by washing with chloroform in good yield [5][33][34]. Stille cross-coupling with the appropriate tributyltin

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

• in Scheme 1, which requires cyclisation from the alkylated N-allylaniline 4. The use of polyphosphoric acid (PPA) in cyclisation reactions is well known in the literature, and has been used to form a large variety of ring structures [15]. Iodination of 3 could then be realised by utilising the rich

• iodination literature available [16][17]. Isopropylation of the inexpensive o-toluidine (5) can be conducted by simply adding NaOH and 2-iodopropane to a refluxing solution of the aniline (Scheme 2). While this straightforward procedure was well suited to larger scale, some bis-alkylation was difficult to

• , presumably due to steric hindrance. Cyclisation of 4 to the THQ 3 was realised by heating a PPA mixture of 4 to 120 °C. Iodination of 3 using a variety of reagents including I2/HgO [19], ICl/AcOH, N-iodosuccinimide/TFA [20], KI/KIO3/AcOH [21], and N-chlorosuccinimide/NaI/AcOH [22], all gave poor yields (0–30

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• , and nitrosyl tetrafluoroborate (NOBF4) (Scheme 3). The deantimonation of 3a with HCl gave 1-benzyl-4-phenyl-1,2,3-triazole (4) in 98% yield. Iodination of 3a using I2 afforded 5-iodo-4-phenyl-1,2,3-triazole (5) in 71% yield. However, the reaction of 3a with Br2 gave a complex mixture. The reaction of

Synthesis of 2-substituted tetraphenylenes via transition-metal-catalyzed derivatization of tetraphenylene

• Shulei Pan,
• Hang Jiang,
• Yanghui Zhang,
• Yu Zhang and
• Dushen Chen

Beilstein J. Org. Chem. 2016, 12, 1302–1308, doi:10.3762/bjoc.12.122

• surveyed the reaction conditions for the iodination of tetraphenylene with NIS (2d). Under the reaction conditions developed by the Wang group, the desired iodinated tetraphenylene 3d was obtained in 18% yield as shown in Table 4 (entry 1). When the reaction was performed at 60 °C, the yield of 3d

• -catalyzed acetoxylation of tetraphenylene (1). The AuCl3-catalyzed chlorination of tetraphenylene (1). The AuCl3-catalyzed bromination of tetraphenylene (1). The AuCl3-catalyzed iodination of tetraphenylene (1). The Pd(OAc)2-catalyzed carbonylation of tetraphenylene (1). Supporting Information Supporting

Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

• William A. Nack,
• Xinmou Wang,
• Bo Wang,
• Gang He and
• Gong Chen

Beilstein J. Org. Chem. 2016, 12, 1243–1249, doi:10.3762/bjoc.12.119

• Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China 10.3762/bjoc.12.119 Abstract A new palladium-catalyzed picolinamide (PA)-directed ortho-iodination reaction of ε-C(sp2)−H bonds of γ-arylpropylamine substrates is reported. This reaction proceeds selectively with a variety of γ

• iodination, and Cu-catalyzed C−N cyclization enables a streamlined synthesis of tetrahydroquinolines bearing diverse substitution patterns. Keywords: iodination; palladium; remote C–H activation; tetrahydroquinoline; Introduction Tetrahydroquinoline (THQ) is an important N-heterocyclic scaffold found in

• provided PA-coupled THQ products in good yields. Although ε-C−H iodination via directed SEAr proceeds with excellent yield and mono-selectivity for many γ-arylpropylpicolinamides, the scope of these PA-directed SEAr reactions is limited to arenes bearing moderate electron-donating or withdrawing groups

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• . These additions proceed in the presence of only 2–5 mol % Pd(PPh3)4 and afford bi- and tricyclic compounds with excellent stereoselectivity and in moderate to very good efficacy. The low mass balance observed in several cases may be due to subsequent reactions such as simple de-iodination of the

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• -iodination at room temperature, where substitution reactions would be unlikely, considering the fact that the substitution has to occur at the sterically congested tertiary iodide 24. However, to our surprise, when C-iodination of 5a was carried out at rt, we found that it also afforded 2-oxindole 4a in 30

Iodine-mediated synthesis of 3-acylbenzothiadiazine 1,1-dioxides

• Long-Yi Xi,
• Ruo-Yi Zhang,
• Lei Shi,
• Shan-Yong Chen and
• Xiao-Qi Yu

Beilstein J. Org. Chem. 2016, 12, 1072–1078, doi:10.3762/bjoc.12.101

• of luotonin F and derivatives from aromatic ketones and 2-aminobenzamides via iodination/Kornblum oxidation/annulation [25]. We envisioned that 2-aminobenzenesulfonamides would undergo a similar reaction to afford 3-acylbenzothiadiazine 1,1-dioxides. Herein, we report the first synthesis of 3

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• –Smith method [13] as illustrated in Scheme 3. For further elaboration, aldehyde 15 was reduced with NaBH4 in good yield to generate the corresponding benzyl alcohol 19 [14]. Iodination of 19 to generate 20 with HI in chloroform [15] proved superior (95% yield) to the more classical Appel protocol which

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• commenced with the preparation of diol 96 by a palladium-catalyzed hydrostannylation of 2-butyne-1,4-diol (95). Regioselective silylation with tert-butyldimethylsilyl chloride of the sterically less hindered alcohol, iodination and silylation of the primary alcohol with trimethylsilyl chloride gave vinyl

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• ). The catalytic iodination of electron deficient 1,3-azoles was recently realized by Zhao et al. Under the catalytic conditions consisting of LiOt-Bu, 1,10-phenanthroline and CuBr2, a class of different conventional azoles 17, including benzoxazoles, benzothiazole, N-methylbenzimidazole, 5-phenyloxazole

• –X containing compounds. Recently, Zhu and co-workers reported a new approach for the synthesis of 2 or 4-iododibenzofurans based on CuI-mediated cascade reactions wherein the C–H iodination and cycloetherification acted as key transformations [55]. As outlined in Scheme 15, in the presence of 1.5

• equiv of CuI and PivOH, the EWG-functionalized o-arylphenols 37 underwent simultaneous C–H iodination and intramolecular C–H o-arylation by heating in DMSO at 140 °C, which led to the production of iodinated dibenzo[b,d]furans in either the form of 38 or 39 depending on the position of the EWG. The CuI

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• )phenylboronic esters, iodo(pentafluorosulfanyl)benzenes and (pentafluorosulfanyl)benzene is shown. Keywords: borylation; diazonium salts; iodination; pyridine; sulfur pentafluorides; Introduction Pentafluorosulfanyl-containing compounds have been known for more than half a century [1][2][3][4]; however, for a

• access to SF5-phenylboronates appears to be starting from readily available SF5-substituted anilines or diazonium salts rather than SF5-containing halobenzenes. Herein, we report a new protocol for efficient borylation, iodination and hydrodediazoniation of SF5-phenyldiazonium tetrafluoroborates in the

• presence of pyridine. The generality of the borylation and iodination reactions was demonstrated on several examples. Results and Discussion At the onset of our investigation, Sandmeyer-type borylation of 3- and 4-(pentafluorosulfanyl)anilines (1a and 1b, respectively) to pinacolboronates 2a and 2b

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