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

• 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

• variety of areas in organic chemistry [56][57]. Recently, Shaabani’s group synthesized and characterized palladium nanoparticles supported on ethylenediamine-functionalized cellulose (PdNPs@EDACs) as a novel bio-supported catalyst for Heck and Sonogashira couplings in water [58]. Shaabani’s group reported

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• desired products have been obtained in good to excellent yields. The nature and the position of the aniline substituent at the aromatic ring influenced the outcome of the couplings. 2-Amino-13α-estrone was also synthesized in a two-step protocol including an amination of 2-bromo-13α-estrone 3-benzyl ether

• in the amination step [9]. They also found that X-Phos is an outstanding ligand with increased activity and stability compared to those based on BINAP [10]. There are a number of literature methods with respect to microwave-assisted Buchwald–Hartwig couplings [11][12][13]. Many publications have

• (dba)3 as catalysts, X-Phos as a ligand, Cs2CO3 as a base in toluene or DMF solvent under thermal heating or microwave irradiation [18]. We recently described halogenations [19] and Sonogashira couplings on ring A of 13α-estrone and its 3-methyl ether [20]. The 13-epimer of natural estrone is a non

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• intramolecular fashion has the double advantage of avoiding homocoupling as well as helping to overcome low reactivity in hindered systems such as cyclohexanone [12]. To the best of our knowledge there are only five examples of successful intermolecular couplings of dissimilar enolates. Two of these examples

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

• letermovir [8]. Hitherto, highly effective systems had been developed for the aryliodines that participated in Heck reactions with turn-over numbers of >1000 [9][10]. However, the couplings of bromo and chloro derivatives with unactivated alkenes still remain challenging. Though aryl bromides are always

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• reference [67]. Suzuki−Miyaura couplings with, or without, ppm Pd. Conditions: ArI 0.5 mmol 3a, Ar’B(OH)2 (0.75–1.00 mmol, 1.5–2.0 equiv) 3b, *with 200 ppm of Pd(OAc)2. Adapted from reference [70]. Copyright 2016 American Chemical Society. Cascade reaction with GOx and Myo. Adapted from reference [82

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• oxide Ce0.99Pd0.01O2–δ showed to be least efficient for the explored Suzuki–Miyaura couplings. Regarding the selectivity of the catalysts in the selected cross-coupling reactions, no bromoarene-deriving side products (dehalogenation product Ar’ and bromoarene homocoupling product Ar’Ar’) could be

• of the catalytic active compounds. To assess the reusability of the heterogeneous catalysts, the Pd-substituted metal oxides were subjected to Suzuki–Miyaura couplings of 4-bromotoluene with phenylboronic acid in five subsequent reactions, i.e., after one reaction was finished, the particles were

• activities for Suzuki–Miyaura couplings in batch [37] and continuous flow [38]. After milling, the coarse and fine fractions of the particles were separated via sedimentation. For this purpose, 2 g of catalyst were suspended in 1 L water, the particles were de-aggregated by ultrasonic treatment and left to

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• amine 9 to compound 11 in two steps. However, under microwave heating conditions, both couplings of the amino group with squarate, as well as methoxymethyl (MOM) deprotection was observed. To the best of our knowledge, there is no report describing methanolysis of MOM-groups under microwave conditions

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• –95%, preferentially with double or triple couplings, and a coupling time of 120 to 300 s [22][27][29]. Conclusion The synthesis of fully protected trimers can be achieved in solution, on a solid phase or on soluble supports. The key element is the choice of a suitable set of orthogonal protecting

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• uracils have also been extensively studied as fluorescent nucleobases in the context of aegPNA. Modifications have invariably been made at the 5-position of uracil, which could be functionalized by various aromatics or alkynes via palladium-catalyzed cross couplings of the corresponding iodouridine

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• with the electric field gradients associated with the orientated media, creating anisotropy and resolving into two sets of doublets. If there is sufficient resolution between these quadrupolar couplings, then the enantiomeric ratio can be recorded. We have used poly-γ-benzyl-L-glutamate (PBLG

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• affected by other contributions, e.g., the non-degenerate coupling between different guanosine transitions, long-range couplings between distant guanosines, etc. More interestingly for our purpose, ECD is a useful method for probing conformational changes of nucleic acid upon ligand binding. Moreover, as

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• support by means of an Fmoc/tert-butyl protecting group strategy on a preloaded Fmoc-Lys(Boc)Wang resin (0.57 mmol/g loading) using 10 mL polypropylene reactors. HfLeu containing peptides were synthesized with an Activo-P11 automated peptide synthesizer (Activotec, Cambridge, United Kingdom). Couplings of

• non-fluorinated amino acids were performed in dimethylformamide (DMF) with the Fmoc-L-amino acid, 1-hydroxybenzotriazole (HOBt) and N,N’-diisocarbodiimide (DIC) in an eight-fold excess with respect to the resin amount. In order to ensure completion of the reaction the couplings were performed twice

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

• ][5][6][7][8][9], Suzuki [10][11][12][13][14][15][16][17][18][19], or Kumada [20] couplings [21] (Scheme 1a and b). However, all these procedures require the preparation of an organometallic or a boron derivative of one of the coupling partners, and provide an organometallic salt (MX) as waste. In

• described. Therefore, the reactivity of 2-bromo- and 2,5-dibromoselenophenes in Pd-catalyzed direct couplings with heteroarenes needed to be investigated. Herein, we wish to report on the reactivity of 2-bromoselenophene, 2,5-dibromoselenophene and 2-aryl-5-bromoselenophenes in palladium-catalyzed direct

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

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• accessible from amino acids, are widely used in these kinds of reactions [13][14][15][16][17][18]. More recent examples demonstrate the applicability in various reactions like diastereoselective α-fluorination [19], total syntheses [20][21], cross-dehydrogenative couplings [22], selectivity-reversed Friedel

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• of the azolo-1,2,4-triazines. The combined analysis of the JHN and JCN couplings in 15N-labelled compounds provides an efficient method for the structure determination of N-alkylated azolo-azines even in the case of isomer formation. The isomerization of adamantylated tetrazolo[1,5-b][1,2,4]triazin-7

• the most efficient way to measure JHN couplings [24]. Previously, the incorporation of a single 15N label in position 1 of the 1,2,4-triazole fragment of compounds 5 and 6 and analysis of the JCN couplings permitted the unambiguous identification of the structures of the N3-adamantylated derivatives

• ]pyrimidin-7-one and the N-adamantylation of the obtained compounds. The combined analysis of the JCN and JHN couplings permitted the straightforward determination of the adamantylation sites in these azolo-azines, even when a mixture of regioisomers is formed. Results Synthesis. Derivatives of 1,2,4

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• alternative approach, we tested the optimal conditions developed previously for peptide mechanosynthesis [25], starting with unactivated amino acids together with a coupling agent. We had indeed reported two successful examples of couplings involving proline amino esters. The initial conditions, using 1-ethyl

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• ]. Developed somewhat later than the aforementioned methods and the couplings of organomagnesium and organotin reagents was the cross-coupling of silanes, pioneered by Hiyama [3][4] and siloxanes [5]. This versatile method has been extensively reviewed [6][7][8]. The cross-coupling of alkenyl silanols [9][10

• . The siloxanes 8 participated efficiently in Hiyama-type cross-couplings with aryl iodides in the presence of Pd2(dba)3 catalyst and tetrabutylammonium fluoride (TBAF, Table 1). Both electron-rich (Table 1, entries 1, 2, and 7) and electron-poor (Table 1, entries 5 and 6) iodides give coupled products

• established in applying the Buchwald–Hartwig coupling to 15, producing the benzoxocane 24, which contains the carbon skeleton of heliannuol A. Retrosynthetic analysis of heliannuol A. Hydrosilylation of alkynols. Hydrogenation of benzoxocane 24. Pd-catalyzed couplings of oxasilacycloalkenes with aryl iodides

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• applications in heterogeneous catalysis [10][11][12][13][14]. Transition metal and metal oxide nanoparticles have been reported to be highly active and selective in several processes, such as redox [15][16][17], C–C and C–heteroatom couplings [18][19]. In particular, iron oxide nanoparticles have been the

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• alkenes were obtained in good to excellent yields using the Na2PdCl4/L1 catalyst system with only a 0.05–0.1 mol % palladium loading. To the best of our knowledge, the catalyst loading in the current report for aqueous Mizoroki–Heck couplings of aryl bromides is much lower than other previously reported

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• and promote the reaction efficiently. Furthermore, the couplings of heteroaryl bromides (1m–o) and styrene (2a) as well as substituted bromobenzene (1i) and butyl acrylate (2f, 2g) were investigated to extend the scope and generality of the reaction. The results clearly demonstrate that all the

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• approach have already yielded some noteworthy successes, which augur rather well for the future of the field. Indeed, the integration of the various components of presumptive pre-cellular entities within single chemical models have led to the discovery of new dynamic couplings between chemicals within a

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• ][11], Suzuki–Miyaura [12][13][14][15] and Stille couplings [16][17][18][19][20][21][22] were successfully applied for this purpose. Direct arylation and alkenylation are modern approaches for the formation of C–C bonds, and the application of these methodologies to porphyrins was widely studied by

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• chemistry, fortunately, is very rich in terms of possibilities for coupling different types of processes and, thereby, its careful exploration is bound to lead us towards proper proto-cellular and proto-metabolic systems (‘a-to-b’ transition in Figure 1). In addition to direct reaction couplings and

• ]), or the dynamic changes they could provoke in the conditions under which the chemistry takes place (e.g., their capacity to generate pH gradients during growth [53] or the ‘osmotic couplings’ they may induce among internal molecular species via volume changes [54]). In any case, all these projected or

• -up synthetic-biology example of how this can be approached, see [55]. Challenge 2: finding conditions and mechanisms for minimal functional integration. A focused search for the specific experimental conditions and the set of molecular interaction mechanisms (physicochemical couplings) that lead to