Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• -imidazol-1-yl)methane (5) was synthesized from imidazole (4) and CH2Br2 following a literature procedure [62][63] with slight modifications. Then, BImNs (N = 4, 10, 12, 14) were synthesized from 5 by mono-alkylation using the corresponding n-alkyl halides in DMF. Finally, PBImNs (N = 4, 10, 12, 14) were

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• water/methanol 1:2 (v/v). These anions caused the bright red solutions of the nanoparticles to change their color because of nanoparticle aggregation followed by precipitation, whereas halides or oxoanions such as sulfate, nitrate, or carbonate produced no effect. The sensitivity of phosphate sensing

• . AuNP-based probes for inorganic anions, for example, can serve to monitor the water quality [14][15]. An example is the probe for halides that was described by the Sessler group. It comprised AuNPs with immobilized calix[4]pyrrole residues that are known to interact with chloride and fluoride. The

• response was observed to hydrogenphosphate (and hydrogenarsenate). Other oxoanions and halides induced no visible effects and also did not interfere in diphosphate and triphosphate sensing when simultaneously present. It should be noted that other strategies of detecting diphosphate anions by using

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• ; catalysis; copper; fluorine chemistry; trifluoromethylation; Introduction The introduction of a trifluoromethyl group is one of the most attractive reactions in drug discovery [1][2]. In the past decade, trifluoromethylation reactions of aryl halides in the presence of transition-metal complexes were

• reported [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. CuCF3 is a useful species for the trifluoromethylation of aryl halides and there are a number of precursors of CuCF3 for trifluoromethylation reactions. In contrast, the catalytic generation of CuCF3 was less investigated [15

• , hexafluorobenzene was added as an internal standard and the mixture analyzed by 19F NMR spectroscopy for the calculation of the NMR yield. Then, the crude products were purified by preparative TLC to give pure products 3. Trifluoromethylation of aryl halides. Scope of aryl iodides. Yields determined by 19F NMR

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• photocatalysts used for this reaction, it is proposed the excited state of 9 is sufficiently reducing to initiate the chain mechanism through an oxidative quench. Moving away from electronically activated halides, MacMillan et al. investigated a tricatalytic system, utilising enamine, photoredox, and HAT

• ). It is notable that pyridyl ketones do not perform well in this reaction (1 example, 70:30 er). A further extension of this methodology includes the deuteration of 128 and alkyl halides 132 using D2O to afford 133 (18 examples, up to >99:1 er) and 134 (34 examples, up to 98:2 er), respectively (Scheme

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• promising building blocks for further functionalization, including (het)aryl or alkenyl substitution at the N1 atom. However, direct arylation of 1 with aryl halides under Ullmann reaction conditions is a low-efficiency process giving only complex mixtures. It is likely that the harsh thermal conditions

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• °C) in the presence or absence of bases (Et3N). Keywords: deep eutectic solvents; imidazoles; phenacyl azides; phenacyl halides; pyrimidines; Introduction In a world with dwindling petroleum resources, the setting up of more and more sustainable routes for the preparation of heterocyclic compounds

• (g) heterogeneous “click” cycloaddition reactions [15] using DESs as environmentally responsible and non-innocent reaction media. Telescoped, one-pot transformations of phenacyl halides to symmetrical 2,5-disubstituted pyrazines (A), through phenacyl azides as intermediates, were also found to take

• separation of the organic layer from water, and removal of the volatiles under reduced pressure. To examine the scope and limitation of this transformation, various functionalized phenacyl halides (1c–i) were tested as substrates. As can be seen from the results compiled in Scheme 3, the reaction is amenable

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• synthesis to access up to –[CH2]10– macrocycles or acyl halides to access up to –[CH2]14– macrocycles. Seventy-five receptor–anion complexes were modelled and studied with COSMO-RS, in addition to all free host molecules. In order to predict initial selectivity towards carboxylates, 1H NMR relative

• anions also represented different parts of the Hofmeister series. Chloride and nitrate are also common in real-world samples that such sensors might be used to analyse. Fluoride and iodide represented halides at opposite ends of the Hofmeister series. The selectivity pattern for the control membrane

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• , hydrolysis of the ester with a mixture of HBr and AcOH gave 2-(perfluorophenyl)acetic acid in a good preparative yield of 63%. A significant advantage of this new approach to 2-(perfluorophenyl)acetic acid is that handling toxic substances such as cyanides and perfluorinated benzyl halides is avoided

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• ., the organic Acr–H2 molecule (Figure 23). In this study, 35 examples of the targeted coupling products were afforded in good to excellent yields. Various synthetically relevant functional groups, including halides, esters, amides, ethers, ketones, and aldehydes were compatible with the protocol. This

• very efficient at room temperature while applying blue LED irradiation. Two slightly modified catalytic systems composed of a [Ru(p-cymene)Cl2]2 catalyst and either K2CO3 or KOAc bases promoted the direct meta-selective C(sp2)–H alkylation with secondary and tertiary alkyl halides, delivering the

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• photocatalyst for the reduction of aryl halides [193]. The material could undergo consecutive photoinduced electron transfers (ConPET) in which the material enters an excited state and is reduced by a sacrificial electron donor (NEt3). The resulting Zn-PDI radical anion then undergoes a second photon absorption

• to achieve a superreducing electronic excited state capable of reducing stable aryl halides (Figure 14) [193]. More recently, PDI self-assemblies have been reported as efficient HPCats for the hydrogen evolution reaction [194] and degradation of phenol [192]. Another important material design applied

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• , or disulfonates of alkane-1,3-diols with sodium sulfide. The intramolecular substitution of 3-mercaptoalkyl halides or sulfonates is a similar strategy for the preparation of thietanes [12][13][14]. Alternatively, inter- and intramolecular photochemical [2 + 2] cycloadditions (thia-Paternò–Büchi

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• combined with a solution-phase reagent, including: (1) copper(I) oxide to produce N-heterocyclic carbene–Cu(I) complexes for use as catalysts [13]; (2) proline to perform proline-based catalytic reactions [14]; (3) zinc powder to produce organozinc halides in tandem with Negishi couplings [15]; (4) zinc

• conversion because the neutralization can alter the aggregation states, producing a significant batch-to-batch variability. The direct insertion of magnesium metal into organic halides is the most common method used to prepare Grignard reagents but present difficulties: (1) sluggish reactions with ordinary

• use a practical system with a broad range of substrates [40][41][42]. The Alcázar group reported the generation and subsequent use of Grignard reagents [40]. In 2018, the Loren group extended the scope of the organozinc reagents made in flow to aryl and tertiary alkyl halides by the in situ formation

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• fragmentation of the reduced intermediates. Due to their availability and their attitude to undergo reductive fragmentations, alkyl halides have been extensively used as C(sp3) radicals sources. Recently, Dell’Amico and co-workers reported a new class of naphthochromenone-based organic dyes, which, due to the

• wide redox window (E = 3.22 eV, +1.65 V/−1.77 V), can be exploited as photocatalysts for various transformations, including the reductive dehalogenation of benzylic halides (Scheme 7) [52]. In this protocol, the excited state photocatalyst OD18 can generate C(sp3) radicals through the reductive

• cleavage of various benzyl halides 7.1 (I, Br, Cl). The radical is then intercepted by an H atom donor (Hantzsch ester), which delivers the corresponding toluene derivative 7.2. Other organic dyes can promote the reductive fragmentation of alkyl halides. For instance, König and Zeitler demonstrated that a

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• -alkynyltrifluoroacetanilides. In all these procedures, the activation of the triple bond was achieved by means of a σ-organyl palladium complex, in turn generated in situ by oxidative addition of a Pd(0) species to suitable organic electrophiles (aryl and vinyl halides or triflates [35][36], alkyl halides [37], alkynyl

• halides [38], α-iodoenones [39], or by transmetalation of a Pd(II) species with boronic acids [33]. In this context, we decided to explore the use of substrates 2 in the reaction with 2-alkynyltrifluoroacetanilides 5 through a sequential cyclocarbopalladation/aminopalladation/reductive elimination process

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• , and aryl halides in the presence of Na2CO3 (2 equiv) using a NiBr2/2,2-bipyridine system [31]. We also developed reactions of imidazopyridines, Se powder, and triarylbismuthanes using a CuI/1,10-phenanthroline catalytic system that did not require a base or an additive [32]. On the other hand, the

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• difluoromethylcopper ones are less stable as demonstrated by the work of Burton in 2007 [37]. Investigations on the in situ synthesis of difluoromethylcopper from a difluoromethylcadmium source at low temperature and the study of its reactivity with various classes of compounds such as allylic halides, propargylic

• halides and tosylates, iodoalkynes and reactive alkyl halides were realized. It was established that CuCF2H readily decompose into 1,1,2,2-tetrafluoroethane and cis-difluoroethylene. From this pioneer work, attention was paid either to the design of new synthetic pathways for the synthesis of a well

• -generated copper-based reagent (19 examples, up to 80% yield, Scheme 7e). With a similar method and in the presence of 1,10-phenanthroline as a ligand, the functionalization of alkenyl halides (8 examples, up to 82% yield), allyl halides (7 examples, up to 99% yield) and benzyl bromides (6 examples, up to

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• reported herein different methods for their synthesis. 1.1. Negishi cross coupling of aryl halide and organozinc compounds Jackson and co-workers reported the synthesis of a range of phenylalanine derivatives via Negishi cross-coupling reactions of aryl halides and Zn homoenolates of the protected (R

• )-iodoalanine 2. The reaction was activated using Pd(0) as a catalyst. A palladium-catalyzed cross-coupling reaction between an organozinc iodide and aryl halides offers a convenient method for the direct preparation of protected fluorinated Phe analogues 3. Thus, cross coupling of the protected iodoalanine 2

• and 12b afforded ʟ-4-[sulfono(difluoromethyl)]phenylalanine derivatives 13a and 13b, respectively [39] (Scheme 3). 1.2. Alkylations of fluorinated aryl halides with a chiral auxiliary Alternatively, the coupling of the bis(dimethoxybenzyl)-protected sulfonamide 14, instead of the esters 10a and 10b

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• halides to get an insight into the specific reactivity of these building blocks. The workflow combined a powerful photoreactor with precise and reproducible conditions control with benchtop analytical tools such as TLC–MS and low-field NMR. This enabled the identification of privileged spirocyclic

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• proceeded efficiently for a wide range of substrates in moderate to excellent yield, including various alkyl halides 93, carbon tetrachloride, 2-norbornene, cyclic alkenes, a terminal disubstituted olefin, and a terminal alkyne. The reaction mechanism was thought to proceed via energy transfer from the

• . Moreover, the excited 4-anisaldehyde (98) underwent energy transfer over the addition to the double bond of the alkene, as no Paterno–Büchi cycloadducts were observed. Furthermore, the detection of the photolysis products of the alkyl halides mentioned above indicated the presence of triplet state 4

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• , electrophilic alkyl radicals were used in several transformations, such as electrophilic cross couplings under nickel catalysis, either with boronic acids [35] or different (aryl)halides [36][37][38]. Furthermore, visible light-promoted uncatalyzed electron transfer via the formation of electron donor–acceptor

• para-substituted product 6 was isolated in 64% yield, and the two sterically more congested products 4 and 5 gave about 10% lower yields (Scheme 2). This went in line with the similarly sterically demanding 2-methylnaphthyl product 7, which was obtained in 50% yield. Halides, such as bromo and fluoro

• substituents had a negative effect on the efficiency of the transformation, independently of their electronic effects (Scheme 3, 21–25). Still, halides, nitriles, and ester substituents were tolerated, giving a possible handle for further manipulation. However, the presence of a nitro group impeded the

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ] are common partners in a variety of important cross-coupling reactions. They are also especially valuable precursors to other functional groups such as organic halides, alcohols [5][6][7], etc. Moreover, recent drug discovery efforts have shifted towards the incorporation of these non-natural

• (Scheme 4). It should be mentioned that secondary triflates or halides are not suitable for this transformation, since they lead to products resulting from fast β-elimination. Considering this limitation, they designed alkyl triflates stabilized by a strong electron-withdrawing group (EWG) directly

• 122. Moreover, the intermediates could be trapped in the presence of electrophiles, such as aldehydes or alkyl halides to afford interesting α-substituted products 124 and 125. This phenomenon was further studied in detail on different dienones [58]. In 2013, Procter and co-workers [59] extended the

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• -functionalized silica 46 was added to the mixture, and this was heated to reflux to generate the catalyst 48. Several organic halides or epoxides, nonactivated alkynes, and sodium azide were reacted in an aqueous medium to provide triazoles or β-hydroxytriazoles using 1.0 mol % catalyst loading at 25 °C

• washed with acetonitrile and dried before being used in “click” reactions. CuI/AK (68) furnished the desired products of the reaction of phenacyl halides (with Me, Br, and Cl substituents), benzyl halides or methyl iodide, and phenylacetylene or propargyl alcohol as substrates using a catalytic amount of

• and organic halides as well as sodium azide were stirred in a mixture of t-BuOH/H2O, 3:1, v/v as the solvent in the presence of diethylisopropylamine and SiO2–Cu. In both cases, the SiO2–Cu catalyst was filtered off and then, the triazole products were purified. In another approach, 2-pyridine

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• groups to form biaryl frameworks. Traditionally, transition-metal-catalyzed cross-coupling reactions of aryl halides or pseudohalides with arylmetal reagents have been employed for the connection of two aryl units [5][6][7][8][9]. However, in search of more efficient synthetic routes, C–H arylation

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• it possible to introduce useful functional groups into the products through the further transformation of corresponding aryl halides. 2-Naphthyliodonium salt could react smoothly with 1a to provide 3p in 66% yield (Scheme 2, 3p). Moreover, thiophen-2-yliodonium salt could be tolerated, albeit with a

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• ]. Having established the synthesis of heterocycle 4 this unsaturated five-membered S,Se-containing compound was used as a starting material for the synthesis of novel ensembles of selenium heterocycles with promising biological activity. The treatment of 4 with organyl halides resulted in the efficient

• with organyl halides. Various substrates were involved in the reaction, providing the introduction of alkyl, benzyl, allyl, and 2-propynyl moieties as well as pharmacophores as 2-pyridylmethyl and 4-fluorobenzyl. A possibility for the synthesis of compounds containing two 1,3-thiaselenol-2

• 1,3-thiaselenol-2-ylmethylselenolate through reduction of the Se–Se bond with NaBH4 followed by nucleophilic substitution with alkyl halides (Scheme 11). Thus, two efficient methods for the preparation of novel 1,3-thiaselenol-2-ylmethylselanyl derivatives 6a–l from selenocyanate 4 and diselenides 8