Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• work focused on the activation of hypervalent iodine [13], and a computational study that suggested a concerted iodination/deprotonation (CID) that is analogous to concerted metallation/deprotonation (CMD) for cationic hypervalent iodine [14]. These studies and others on the electrophilic nature and

One-pot synthesis of diaryliodonium salts from arenes and aryl iodides with Oxone–sulfuric acid

• Natalia Soldatova,
• Pavel Postnikov,
• Olga Kukurina,
• Viktor V. Zhdankin,
• Akira Yoshimura,
• Thomas Wirth and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 849–855, doi:10.3762/bjoc.14.70

• -donating or electron-withdrawing groups in good yields. In addition, this procedure can be applied to the preparation of symmetric iodonium salts directly from arenes via a one-pot iodination–oxidation sequence. Keywords: diaryliodonium salts; iodine; iodonium; oxidation; Oxone; Introduction

• because of the low solubility of these products (Table 3). Finally, a one-step procedure for the preparation of symmetric iodonium salts directly from arenes via an in situ iodination was developed (Table 4). Arenes 2b–e can be transformed to the symmetric iodonium salts 3b and 3t–v by the reaction with

• iodine, Oxone, and sulfuric acid. The attempted synthesis of the symmetric iodonium salt using toluene as substrate led to a regioisomeric mixture of products due to the low regioselectivity of iodination. This procedure allowed the synthesis of iodonium salts with arenes containing electron-donating

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp² C–H bond activation in ball mills

• Zi Liu,
• Hui Xu and
• Guan-Wu Wang

Beilstein J. Org. Chem. 2018, 14, 430–435, doi:10.3762/bjoc.14.31

• . China 10.3762/bjoc.14.31 Abstract A solvent-free palladium-catalyzed ortho-iodination of acetanilides using N-iodosuccinimide as the iodine source has been developed under ball-milling conditions. This present method avoids the use of hazardous organic solvents, high reaction temperature, and long

• ][24][25][26][27][28]. A few mechanochemical ortho-C–H bond activation reactions under the catalysis of rhodium and palladium salts have been reported [29][30][31][32][33][34][35][36][37][38]. Hernández and Bolm reported the rhodium-catalyzed bromination and iodination of 2-phenylpyridine using N

• ], we have independently investigated the solvent-free ortho-iodination of acetanilides under ball-milling conditions [45]. In addition, the current reaction can be extended to ortho-bromination and ortho-chlorination by using the corresponding N-halosuccinimides. Herein, we report these regioselective

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• . The reaction of 5-amino-4-cyanopyrazole (208) and formamide was carried out by Todorovic et al. [136] under microwave irradiation at 200 °C to give 4-aminopyrazolo[3,4-d]pyrimidine (223) which on iodination with N-iodosuccinimide followed by N1-alkylation (Mitsunobu or substitution) provided

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• . For the iodination step, the authors proposed that the β-CF3 alkyl radical was intercepted by I2, which was formed by a multistep redox process from I2O5. In continuation of this work, the same research group described the bromotrifluoromethylation of alkenes under similar reaction conditions but

•  29b) [51]. A single-electron oxidative free-radical process was ascertained for the generation of CF3•. From enynes, the iodination step was realised by I2, which was formed by a multistep redox process from I2O5. The intramolecular carbotrifluoromethylations of alkenes from acrylamides and

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• equiv) in DMSO at 140 °C. As shown in Scheme 6 (top), the bis(perfluorohexyl) adduct 1,3-(Rf6)2C6H4, which was the undesired byproduct in Scheme 5 (top), was isolated in 75% yield. Subsequent iodination using NIS in fuming H2SO4/CF3CO2H afforded the "all meta" iodide 1,3,5-(Rf6)2C6H3I in 77% yield. The

• with the iodination of 1,3-(Rf6)2C6H4, in which the substituents function as meta directing groups. As shown in Scheme 6, reactions of C6F6 or perfluoroheptane solutions of 1,2,4-(Rf8CH2CH2)2C6H3I and NaOCl/HCl gave the corresponding iodine(III) dichloride 1,2,4-(Rf8CH2CH2)2C6H3ICl2 [50] as a white

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• , Maoming 525000, P. R. China. Fax: +86-668-2923575; Tel: +86-668-2923956 10.3762/bjoc.13.200 Abstract We developed a direct vicinal difunctionalization of alkenes with iodine and TBHP at room temperature. This iodination and peroxidation in a one-pot synthesis produces 1-(tert-butylperoxy)-2-iodoethanes

• applications and allow further chemical modifications, enabling the preparation of synthetically valuable molecules. Keywords: difunctionalization of alkenesiodine; iodination–peroxidation reaction; TBHP; Introduction Alkenes have attracted considerable interest in recent years as abundant, simple chemical

• methods to construct peroxides are still highly desirable and valuable, and highly regioselective and efficient syntheses of peroxides with structural control are still difficult to achieve. Herein, we report a metal-free iodination–peroxidation reaction for the direct vicinal difunctionalization of

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• additional hour. The reactions were routinely performed from 1 mmol of the starting materials, but two of them (leading to compounds 1a and 1n) were also carried out at a 10 mmol scale without any significant loss in yield. This solvent-free protocol combines the initial α-iodination of the starting ketone 4

• to give pyrrole derivatives 1. In some cases (compounds 1d, 1g, 1j, 1l, 1m, 1o), the ball milling-promoted iodination step failed and it was necessary to obtain the α-iodoketones 6 in a separate step by treatment of 4 with I2 and CuO in methanol. The iodination of 1-indanone (eventually leading to 1o

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• ) under solvent-free ball milling condition [88]. Aryl rings containing electron donating groups worked efficiently to yield 70–98% of mono or dibromo derivatives within 2 h. Similarly, NIS led to aryl iodination in near quantitative yield and NCS failed to produce any chlorination product (Scheme 25

• ). However, NCS-cericammonium nitrate (CAN) successfully yielded mono-chlorinated products [88]. Consecutively, the same group reported metal-free oxidative iodination of electron rich aromatic rings with molecular iodine and oxone (Scheme 25) [98]. This method proved to be highly chemoselective and no

• benzylic iodination could be observed in case of alkyl benzenes. Interestingly, benzaldehyde derivatives did not lead to any over-oxidation to acids in presence of oxone. Trihaloisocyanuric acids are also used effectively for halogenations of arenes and 1,3-dicarbonyl compounds and double bond-containing

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• derivative D2 performs best for this purpose, even with rather low catalyst loadings, but it has to be admitted that in general the enantioselectivities are lower than in the two other case studies shown in Scheme 6 [92]. α-Bromination and α-iodination reactions Asymmetric α-bromination and α-iodination

• opinion this field still requires further improvements. By looking for example on the difficulties in achieving high selectivities for asymmetric α-bromination or α-iodination reactions, it becomes clear that new methods are urgently required. Another application that may become of future interest could

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