1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• vinylphosphonium ion, and a proton transfer finally yields the 1,4-betaine. A kinetic study of the PPh3/DMAD/Meldrum’s acid reaction by spectrophotometric and stopped-flow methods has been published [14]. The initial 1,3-betaine has also been trapped with other electrophiles. The stable 1,4-betaines betaines III

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• added the double Grignard reagent 4 to methyl esters 5 [26]. A similar approach was established by Lavis, herein electrophiles (anhydrides or esters) were added to lithium or magnesium organyls 4 [27]. Johnsson and co-workers could establish dye formation by addition of aryllithium 7 to the silicon

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• metalation at C-5 with TMPMgCl∙LiCl at −40 °C. Quenching with various electrophiles gives a broad range of 5-substituted products, which are building blocks for the synthesis of heterocyclic natural products and analogues thereof. In combination with a Parham-type cyclization a novel approach to pyrido[4,3,2

• ] (Figure 2C). The successful directed remote metalation of 4-arylbenzo[c][2,7]naphthyridines 10 prompted us to investigate direct ring metalation of the readily available 4-bromo intermediate 9d [14]. Trapping of the envisaged 5-metalated intermediate with various electrophiles, followed by transformations

• hindered amide base TMPMgCl∙LiCl as crucial step, the Knochel–Hauser base was again the metalation reagent of our choice. Metalation of 4-bromobenzo[c][2,7]naphthyridine (9d) using 1.1 equivalents TMPMgCl∙LiCl at −40 °C, followed by the reaction with various electrophiles gave, in most cases, the expected

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• –CF3 bond formation and Cu(OAc)2 can increase the catalytic turnover (Scheme 63). Based on three different modes of the ArPd(II) species reaction with nucleophiles, electrophiles and highly oxidizing reagents, three possible reaction pathways (A, B and C, respectively) are envisaged, that can follow

• trifluoromethylation of triflate electrophiles, while the use of TESCF3 and RbF gave better results for nonaflate electrophiles. Subsequently, the Yu [15][125] and Shi group [126] independently reported the palladium-catalyzed ortho-trifluoromethylation of an aromatic C–H bond with Umemoto’s trifluoromethylation

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• are thermally unstable, sensitive to oxygen [7][14][49][50][51][52][53][54][55], and photosensitive [42][54][56][57]. Fulvenes react with both nucleophiles and electrophiles (according to frontier orbital theory) [1][2][58], and are prone to acid- and cation-catalysed polymerisations [7][14][44][55

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• ][20][21][22][23]. These carbonyl-substituted heteroarenes possess basic sites (nitrogen or oxygen atoms of the heterocyclic system), which are fully protonated in acid, so that upon subsequent protonation of the carbonyl oxygen, more reactive dicationic electrophiles can be generated. Previously

• should be reactive electrophiles. While, in the case of hydroxyalkylbenzimidazoles 3–8, N,O-diprotonated species III, V, VII, VIII, the most probably, may be reactive intermediates. The calculation of electrophilic properties of these cations show that species I and II have higher values of

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• sufficiently acidic media, cationic electrophiles such as the nitronium ion may undergo protonation, leading to the nitronium dication (1), and a greatly enhanced electrophilic reactivity. In superacidic solutions, nitronium salts have been shown to react with deactivated arenes and saturated hydrocarbons

• electrophiles based on the triarylmethyl cation scaffold (3–5, Scheme 1) [11][12]. These systems utilized pyridyl rings to produce increasing amounts of positive charge adjacent to the carbocation center. Both theoretical calculations and experimental results indicated that the carbocation center undergoes a

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• electrophiles, such as sulfenyl, selenyl, and telluryl chlorides, were used in reactions with these allenes. However, only a few studies have been focused on reactions of phosphorylallenes with Brønsted acids [11][12]. These reactions proceed through an intermediate formation of the corresponding 2,5-dihydro

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• work, which concluded that only especially reactive halides (methyl, benzylic, allylic) were feasible electrophiles; with iodoethane, 1-iodo-2-methylpropane and chloromethoxymethane no alkylation products were formed [17][18][19]. Given these rather discouraging observations in the context of our

• is not readily deprotonated at −78 °C. Clearly, monoalkylated tartrate can be deprotonated and trapped with electrophiles if the system is warmed above −78 °C: to −30 °C by Molander and Harris [29], whereas −50 °C was sufficient for the enolate oxidation steps in Scheme 6 and Scheme 7. Indeed

• tartrate 41 in 71% yield, and used only a slight excess of tartrate 7 and LDA (1.2 and 1.5 equiv, respectively) for 72 h at −78 °C [13]. These examples demonstrate the viability of the tartrate alkylation chemistry with more complex and valuable electrophiles. While monoalkylated tartrate acetonides were

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• aniline is needed to induce the β-elimination (see Scheme 1) and to prevent the side product 1 from reacting with the deprotected ODN via Michael addition [40]. Aniline is a weak base and only mildly nucleophilic. Electrophiles that are compatible with ODNs but reactive toward it are rare. However, using

• a large excess of aniline could be a significant drawback. For example, many electrophiles could be considered unreactive to it, but in the presence of a large excess of it, problems might arise. In addition, its boiling point is high, alternative techniques other than simple evaporation has to be

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• , bottom reaction). We next decided to extend the scope of this strategy to dialkyl-3-oxoglutarates I as the bis-nucleophile partners [33] in the reaction with cyclic α,β-unsaturated-γ-oxycarbonyl derivatives II as the bis-electrophiles (Scheme 2). Interestingly, this new bis-nucleophile/bis-electrophile

• optimized conditions A, at room temperature in DMSO, the six- (2a) as well as the seven-membered (2c) bis-electrophiles reacted smoothly giving the furocycloalkanones 4a and 4c in good yields (Scheme 3). Furthermore, the protocol could be scaled up to 1 mmol without significant yield erosion. Treatment of

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• the synthesis of acyclic nucleoside phosphonates including mesylates [42], tosylates [16][43][44] and alkyl chlorides [45][46][47][48][49][50][51]. Alkylation reactions conducted with these electrophiles generally require higher temperatures. Furthermore, these reagents typically afford products in

• low to moderate yields as the reactions fail to reach completion or else furnish multiple side-products. The successful application of such iodide-based electrophiles is precedented, as demonstrated by the work of Ubasawa et al. in their preparation of purine analogue 17 from 15 (Scheme 3) [52]. A

• favoured alkylation at N7 and 29 was isolated in 79% yield following purification by column chromatography (Scheme 6c). Pal and co-workers previously reported the N7-selective alkylation of 28 using other electrophiles [56]. They confirmed that the reaction had occurred at N7 via HMBC analysis and the

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• cyclopropylmetal species reacted with retention of configuration with those electrophiles opening a new approach to O-heterosubstituted cyclopropyl rings. Experimental General procedure for the carbocupration reaction of 3a,c with RCuCNLi To a suspension of CuCN (1.5 equiv) in 8 mL of Et2O was added alkyllithium

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• F that reacts with electrophiles at C-1. The three-component reaction with nitriles and carboxylic acids then leads to the corresponding β-ketoenamides KEAr in moderate yields. The reaction sequence is illustrated in Scheme 7 also showing the three products KE78 [22], KE79 [45] and KE80 [46] that

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

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• isomerized into 1-methyl-3,3-difluorocyclopropene (A”) [21] (Scheme 1, reaction 1). Another approach relies on the reaction of cyclopropenylmethyl organometallic species C with electrophiles through an SE2’ process leading to substituted alkylidenecyclopropanes D (Scheme 1, reaction 2). Examples of those

• transformations include the carboxylation of a (trimethylsilylmethyl)cyclopropene in the presence of a fluoride promoter [22], and also the addition of electrophiles to (lithiomethyl)cyclopropenes generated by lithiation of the corresponding methylcyclopropenylsulfone [23] or -sulfoxide [24]. More recently, the

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• cyclopropanecarboxaldehydes [10] or reactions of metallated vinylcyclopropanes with suitable electrophiles are commonly employed (Scheme 1a) [11][12][13]. In a more convergent approach where the cyclopropane ring is created at the last stage, divinylcyclopropanes can be prepared by cyclopropanation of 1,3-dienes with metal

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• , its isolation should be possible and enable further modification, for example by ipso-substitution with heteroatom electrophiles. The application of the boronic acid in Suzuki–Miyaura coupling should also be possible [30][31]. Growth inhibition experiments against S. aureus showed that HQNO

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• acrylonitrile derivative 1 or by an Sn/Li transmetalation reaction of n-butyllithium (“n-BuLi”) with the α-stannyl derivative 3. Due to intermolecular LiN coordination, 2Li was deduced [4] to form a clustered ground state that showed no obvious rate anomaly with previously [4] studied electrophiles; this should

• )–MgBr with many electrophiles. In most of the above trapping experiments, a slow disproportionation of t-BuCH=O was observed to generate t-BuCH2OH and t-BuCO2Li as side-products. The adduct 18 (Scheme 4) of fluoren-9-one (15) had again a triangular ligand-binding system at C-α, as shown by the

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

• amino group able to react with a large variety of electrophiles and is commonly used in click reactions [33]. At first, 6A-azido-α-CD 7 was prepared via bromination of α-CD (as previously described for direct bromination) [28]. Then, 6A-azido-6X-mesitylenesulfonyl-α-CD 8 was prepared (reaction 6, Scheme

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• using various electrophiles such as alkyl halides [13], vinyl halides [14][15][16], aryl halides [17][18] and epoxides [19][20] in homogeneous solutions (Figure 1b). 1-2. Design of biomimetic and bioinspired B12 catalytic systems Schematic representations of B12 enzymes and enzyme-involving systems are

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• electrophiles are reacted with the sodium enolate of ethyl acetoacetate, generated from sodium hydroxide, in warm N,N-dimethylacetamide resulting in the formation of substituted quinolines. A degradation–build-up strategy of the ethyl ester at the 3-position allowed for the construction of the α-hydroxyacetic

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• hydrocarboxylation of styrene derivatives has been achieved. Furthermore, the formation of pyrones from diynes and CO2 can be effectively catalyzed by Rh complexes. Review Cobalt catalysts Carboxylation of propargyl acetates Allyl and propargyl electrophiles, such as halides and esters, are well known as efficient

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• -catalyzed reaction of 15a with aldehydes as electrophiles resulted in the divergent formation of 11H-indolo[3,2-c]quinolines 17 (Scheme 5b) [32] through functionalization of C-3 position of the indole ring instead of N-1. The sequential reaction shown in Scheme 5, path a, probably occurs through cyclization

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• generated by the reductive coupling of in situ-formed RCF2CF2MgCl·LiCl with various electrophiles [22][23]. Our group revealed that commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene (1) underwent a Cu(0)-mediated cross-coupling reaction with aromatic iodides in DMSO at 160 °C in a sealed-tube

• also suitable electrophiles to form the respective products 6j and 6k in high-to-excellent yields. Conclusion We developed a novel and practical tetrafluoroethylenating agent, viz. CH2=CHCF2CF2ZnBr (2-Zn), which can be prepared in large-scale and stored for at least 1.5 years in the refrigerator