Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• reagent (Ag2CO3 on Celite) [36][37]. The bromination and glycosylation reaction steps had to be performed in separate reactions. Therefore, we also investigated glycosylations with the respective imidate glycosyl donor 5. First, the cleavage of the anomeric acetyl group with hydrazine acetate was

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• + chemistry. Finally, Lee et al. [27] studied in detail the regiochemical outcomes of the synthesis of the bromosugars 7a and 7b of the glycosylation of Nam (1a) with these bromosugars as well as the deprotection of the acylated nucleosides 8a,b. It was observed that the bromination of 2a with HBr gas in

• β/α mixture was obtained when 2a was reacted with neat bromotrimethylsilane at room temperature. Bromination of 2b yielded a 10:1 β/α mixture of the anomeric bromide 7b [27]. The reaction between Nam (1a) and the bromide 7a was carried out in liquid SO2 and proceeded in high yields with the

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• carried out with inexpensive reagents and can also be applied to the distal bromination of cycloalkanols. The possible mechanism is outlined in Scheme 28. The cycloalkoxy radical 98 is generated from cyclopropanol 91 under the action of the metastable Ag(II) species, which is formed by the interaction of

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• -hydroxy-L-glutamic acid derivative 66 (Scheme 16) was required and it was obtained as a single diastereoisomer from 65 in the same way [75][76]. By bromination of L-glutamic acid Bromination of N-phthaloyl-L-glutamic acid [(S)-67] followed by methanolysis gave a 2:1 mixture of threo and erythro

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• procedure published by Liu et al. [56] and bromination to the new benzyl bromide 9 succeeded with tribromoisocyanuric acid (TBCA) as published by de Almeida et al. [57]. The final transformation of benzyl bromide 9 to triphenylphosphonium charge-tagged 4∙Br was performed with a slightly modified protocol

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• regioisomers on the primary rim of homobifunctionalized diazido-α-CDs by selective substitution on the primary rim. Specifically, three positional regioisomers 6A,6B-, 6A,6C-, and 6A,6D-diazido-α-CDs were prepared via different intermediates (using sulfonylation with capping agents, bromination and tosylation

• prepared all possible regioisomers of primary rim-disubstituted α-CD derivatives using the most common CD intermediates by commonly used derivatization (bromination, tosylation and capping). The three positional isomers (AB, AC, AD) were separated by ad hoc-developed HPLC methods, and the regioisomeric

• ). On one hand, a direct bromination of α-CD was performed under Vilsmeier/Haack conditions (reaction 3, Scheme 2) with N-bromosuccinimide (NBS) and Ph3P in N,N-dimethylformamide (DMF). Previous studies have shown that this reaction is highly regioselective for the primary rim of CD [28]. After a fast

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• benzyl bromides 8–11, which were commercially available or synthesized by radical bromination. The S-diazocines precursors 13–16 were then subjected to the intramolecular Baeyer–Mills reaction yielding the S-diazocines 1–4. In the first step the nitro group was reduced with zinc powder to the

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• (in,in/out,out)-2·2BH3 (2%). Four of these structures are verified by independent syntheses. Second, 1,14-tetradecanedioic acid is converted (reduction, bromination, Arbuzov reaction, LiAlH4) to H2P((CH2)14)PH2 (10; 76% overall yield). The reaction with H3B·SMe2 gives 10·2BH3, which is treated with n

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• -disubstituted-α-hydroxy-carboxylamides, was disclosed by Gulder and co-workers [76]. This catalytic system was applied to the bromination of alkenes by Gulder and co-workers. For example, the iodine(III)-catalyzed halocyclization of methacrylamide 68 generated the brominated oxindole 69 (Scheme 20) [77]. In

• ]. Oxyarylation of alkenes [71]. Asymmetric oxidative rearrangements of alkenes [72]. Bromolactonization of alkenes [75]. Bromination of alkenes [77][78]. Cooperative strategy for the carbonylation of alkenes [79]. Acknowledgements We are grateful for financial support from the National Nature Science Foundation

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• with allyl or propargyl bromide to obtain C12 and C13. In another way, cinchonidine was reduced by H2/Pd/C to yield dihydrocinchonidine, and then reacted with 4-trifluoromethylbenzyl bromide to obtained C14. C15 was prepared from cinchonidine via bromination, debromination and condensation with 4

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• (Scheme 8). After bromination of 40 with molecular bromine in carbon tetrachloride, direct dehydrobromination with lithium chloride in dimethylformamide gave 11 in 85% isolated yield. Müller’s group reported an alternative synthesis for 11 starting from the carbene adduct 41 over two or three steps [55

• benzotropylium ion 45. Secondly, 11 is obtained in 18% yield after benzylic bromination of 42 with NBS, followed by in situ elimination reaction of the labile bromide 43 mediated by t-BuOK (Scheme 9). Palladium-catalyzed C–C bond-formation reactions such as Heck and Sonogashira couplings are employed in a wide

• method for the synthesis of 2,3-benzotropone (12) starting with 1-benzosuberone (162) (Scheme 29) [134]. First, the unsaturated ketone 163, which is called Julia’s ketone, was prepared by NBS-bromination in the presence of a trace of benzoyl peroxide (BPO) and followed by dehydrobromination. Another

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• our previous study on the bromination of enamides [11]. Thus, using a slight excess of DIB along with a two-fold amount of lithium bromide at 0 °C in dry acetonitrile rapidly yielded dibromo adduct 2a in 91% yield (Table 1, entry 1). Switching the reaction conditions to bromo(trifluoro)acetoxylation

• transformations (dibromination, bromo(trifluoro)acetoxylation, bromohydroxylation, iodo(trifluoro)acetoxylation and ene-type chlorination) which were applied to substrates 1b–e in order to explore their scope. Bromination Dibromination Application of the dibromination protocol to neryl acetate (1b) proceeded

• did isolate dibromo adduct 2a but only with 47% yield and we also observed the formation of various byproducts such as ene-bromination adduct 6a’ (Scheme 7b) [27]. Moreover, for the iodination of enamides using the PIFA/KI combination we had already shown that the observed reactivity is more akin to

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• bisacetoxy bromate(I) [73], respectively, rather than the desired bromo radical. As a result, bromination at the aromatic ring of substrate 1a occurred when LiBr was used (Table 1, entry 2), while no reaction was observed in the other two trials using organic bromides (Table 1, entries 3 and 4). At the

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• broad utility of this method, a concise synthesis of axitinib, eutherapeutic drug for the treatment of renal cell carcinoma, was undertaken (Scheme 6). The reaction started from commercially available 6-bromo-1H-indazole (5), bromination of the 3-position and N-protection gave 3,6-dibromo-1-(tetrahydro

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

• ][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

• N-halosuccinimides. The influence of the milling frequency on the reaction of 1a with NIS. Palladium-catalyzed ortho-iodination of 1a in toluene. Plausible mechanism. Palladium-catalyzed ortho-bromination and chlorination of 1a in a ball mill. Optimization of the reaction conditions.a Substrate

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• employed to prepare 2-heteroarylated selenophenes; whereas, 2,5-dibromoselenophene generally gave 2,5-di(heteroarylated) selenophenes in high yields using both thiazole and thiophene derivatives. Moreover, sequential catalytic C2 heteroarylation, bromination, catalytic C5 arylation reactions allowed the

• 2,5-dibromoselenophene and an excess of 1-methylpyrrole, the expected 2,5-diarylated selenophene 14 was obtained in 81% yield. Finally, we show a sequential transformation leading to 2-aryl-5-(heteroaryl)selenophenes in three steps from commercially available compounds (Scheme 4). Bromination at the

• selenophenes in high yields. We also described that the sequential catalytic C2-arylation, bromination, and catalytic C5-arylation of selenophene provides the controled double (hetero)arylation at the C2 and C5 positions of selenophene in good yields. Experimental General procedure for palladium-catalyzed

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• bromination of the α-carbon using CBrCl3 as the Br source. This in situ halogenation strategy has been employed for the synthesis of quinoxalines [23], oxazoles [24][25], pyrido[1,2-a]benzimidazoles [26], imidazo[1,2-a]pyridines [27][28][29][30], thiazoles [31][32] and benzothiazoles [33][34]. With weak

• bicarbonate bases, direct bromination of the α-carbon does not occur. Instead, the Br is shuttled to the α-carbon by its coupling partner. With this tandem bromination and cyclization strategy, there is no need to presynthesize substrates, thus reducing the number of synthetic steps, time, chemicals and

• wastes. Here we describe the extension of this α-bromination shuttle system to 2-aminobenzothiazoles as substrates to synthesize benzo[d]imidazo[2,1-b]thiazoles. The benzo[d]imidazo[2,1-b]thiazole backbone is found in many bioactive molecules and pharmaceutical compounds as evident by its use as

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• triphenylphosphine with 1-bromoethylbenzene. The resulting phosphonium salt 11 was then deprotonated to the corresponding ylide 12, which in the last step was subjected to bromination to give the expected α-bromoethylphosphonium bromide 13 [10]. 1.3. Peterson olefination of α-trimethylsilylphosphonium ylides with

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• significantly increased solubility [32]. It should be noted that other alkylating reagents, bases, and solvents provided the desired products with much lower yield and purity. Subsequent treatment of 7 with N-bromosuccinimide (NBS) smoothly afforded dibromo derivative 8 with a high yield of 93%. Bromination of

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• with acetic anhydride to give fully protected galactose 1 as an anomeric mixture. The α and β anomers (3:7 molar ratio) were identified by NMR. To synthesize bromide 2, we used TiBr4 as a bromination agent. Bromide 2 was obtained as a mixture of α and β anomers (1:4 molar ratio) and was used directly

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method. Keywords: amination; bromination; carboxylation; mechanochemistry; poly(ethylene glycol); solid state; thiolation

• ). 2D-HSQC was performed to validate terminal bromo functionality showing a cross-peak at 1H, 13C = 3.45 ppm, 30.10 ppm (Figure S3, Supporting Information File 1). These results are exciting given that PEG bromination is often performed under harsh conditions either via radical intermediates or using

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

• significant in organic synthesis because aryl halides are important synthons for the synthesis of many natural and non-natural products [93][94]. In 2005, Rahman and co-workers reported a pioneering solid state benzylic bromination of diquinoline derivatives via N-bromosuccinimide (NBS) [95]. In 2012, Wang

• and co-workers reported bromination of phenol derivatives, chalcones, 1,3-dicarbonyl compounds using NaBr as bromine source and oxone as oxidant under ball-milling conditions [96]. Within 1 h they could isolate more than 90% of mono or poly-brominated products of phenol and 1,3-dicarbonyl compounds

• (Scheme 23). α,β-Unsaturated carbonyl compounds could also undergo a trans-bromination reaction efficiently within 40 min. Following to Wang’s report, Stolle and co-workers also reported a similar method of aryl bromination and chlorination using NaBr and NaCl, respectively, in the presence of oxidizing

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

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• functional groups in a chiral molecular skeleton were applied to the enantioselective synthesis of axially chiral benzamides via aromatic electrophilic bromination. The results demonstrate the versatility of bifunctional organocatalysts for the enantioselective construction of axially chiral compounds

• axial chirality [36][37]. Thus, we assumed that this method could be further applied to the enantioselective synthesis of a range of axially chiral compounds. In this study, we present the enantioselective synthesis of 3-hydroxybenzamides via aromatic electrophilic bromination [28][29]. The 3

• material was recovered (see Supporting Information File 1 for details). These results imply that the first bromination, occurring at the ortho-position of the axis (probably at the 2-position), is the enantiodetermining step of the reaction. Moreover, once one of the ortho-positions is brominated