Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• oximes can be achieved through different ways including addition of electrophiles to the C=C double bond of the unsaturated oxime followed by intramolecular nucleophilic attack of the oxime group [97][98][99][100], metal-catalyzed cyclization [98][101][102][103][104][105][106][107][108], cyclization

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

• strong electrophiles and undergo nucleophilic additions with two-electron donors (Scheme 21a) [93][94]. In contrast, radical anions can act as very strong single-electron nucleophiles and are often subject to fragmentation to give a neutral free radical and a charged species (Scheme 21b) [77][95]. When a

• radicals Thiyl (sulfenyl) radicals Thiyl radicals are common, versatile, strong nucleophilic radicals. They are efficient at performing atom abstractions, in particular with H-atoms, adding to π-systems and electrophiles, such as carbonyl compounds [166]. They can be generated from the UV irradiation of

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

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

• 53a,b and 81 were synthesized by Knoevenagel condensation of methyl isocyanoacetate (79) and the corresponding fluorinated benzaldehyde derivatives 50a,b, and m-fluorobenzaldehyde (78) as electrophiles in the presence of catalytic amounts of Cu(I) and base. The cinnamate derivatives 80a–c obtained

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

• aliphatic acids and the coupling of the residual chain with various electrophiles. Metal-based catalysts are common in reactions that require a high redox potential for a single electron transfer (SET) procedure to take place. On the other hand, even if organocatalysts have lower redox potentials, they are

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• advantages of this protocol. Keywords: C–C-bond formation; C3-funtionalization of indole; diindolylmethane; Friedel–Crafts reaction; indole; indole-3-carbinol; large-scale synthesis; recyclability; Introduction (1H-Indol-3-yl)methanols have emerged as versatile pre-electrophiles for C–C functionalization

• cycle. 3-Indolylmethanols are versatile pre-electrophiles for C–C functionalization at the 3-position of indoles. Particularly, the Friedel–Crafts alkylation of 3-indolylmethanols with indoles has become a useful method for the preparation of 3,3'-, and 3,6'-DIMs, which are known to possess a wide

• protocol for the preparation of trifluoromethyl(indolyl)phenylmethanols, which are of significant interest serving as pre-electrophiles for C–C functionalization at the 3-position of indoles. Particularly, the Friedel–Crafts alkylation of 3-indolylmethanols with indoles has become a useful method for 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

• silyl ethers 89–92 (Scheme 18), thus showcasing the synergistic relationship between Pd and Cu catalysis [43]. Driven by the success of earlier results, the authors utilized 78 for reductive couplings between ketones 93 and imines 97 as electrophiles to form unsymmetrical 1,2-diols 94–96 and 1,2-amino

• 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

• enantioselectivity was reported by Hartwig et al. in 2016 [99]. The newly formed C–B bond reacted with a range of electrophiles to deliver products containing C–C, C–N, and C–X (X = Br, Cl) bonds (e.g., 349, 350). Efforts to explore the mechanism revealed a decrease in regioselectivity when the C=C bond is further

Direct borylation of terrylene and quaterrylene

• Haruka Kano,
• Keiji Uehara,
• Kyohei Matsuo,
• Hironobu Hayashi,
• Hiroko Yamada and
• Naoki Aratani

Beilstein J. Org. Chem. 2020, 16, 621–627, doi:10.3762/bjoc.16.58

• quite limited because they must suffer the harsh conditions of the rylene skeleton preparation. Basic reactivity of rylenes with electrophiles is predicted from perylene in which the most reactive sites are the 3,4,9,10-positions [21]. On the other hand, the regioselectivity of the iridium (Ir

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• nature of BODIPY, the reactivity of the 2,6-positions is intrinsically low toward electrophiles, which hampers the β-selective functionalization. We, therefore, tested the corresponding reaction using tetramethyl-substituted BODIPY 1b that is expected to have an enhanced electron density of the BODIPY

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• related coupling reactions [2][3][4]. Although there are many reports on alkyne transformations, one recent development in this area has been the reaction of alkynes with tertiary alkyl electrophiles to produce functionalized quaternary carbon atoms via addition [5][6][7][8][9][10] or coupling [11][12][13

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• vinyl sulfones as electrophiles (Scheme 3). Of note, both the anti- and the syn-product could be predominantly formed (with a anti:syn ratio from 83:17 to 15:85), and no diastereocontrol occurred in the absence of the organocatalyst. Interestingly, this simple protocol was successfully applied to the

• enantioselective synthesis of valnoctamide, a commercialized mild tranquilizer. Finally, this methodology was extended to the sequential Michael/halogenation reaction using NFSI or NCS as electrophiles, with similar efficiency. Similarly, a cocatalyzed enantioselective β-functionalization of enals was developed by

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• functions describe better soft–soft interactions between nucleophiles and electrophiles [8][37][38]. The charge density was calculated for both methods using the Merz–Singh–Kollman scheme (MK) [39][40]. For the calculation of Fukui functions, besides the known computation of differences in atomic charges

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