Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• -unsubstituted 2,3-dihydroisoxazoles in moderate to very good yields, starting from readily available 5-acetoxy- and 5-hydroxyisoxazolidines [7][8]. Their reactivity in electrophilic addition reactions allows for a straightforward introduction of a hydroxy group at the C-4 position of the resulting

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

• radicals are electrophilic, with the substitution playing an important role [133][134][135]. As they are prone to efficient HAT, C(sp3)–H couplings at remote positions have been intensively studied [128][130][132][136]. Aminyl and aminium radicals display the opposite philicity: aminyls are nucleophilic

• , whereas upon protonation, the generated aminium is strongly electrophilic. N-Centred radical cations have been employed as key intermediates in amine syntheses [137][138]. These species can further react, according to the structure of the substrate, to form either iminium ions or C-centered radicals, such

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

• experiments, a plausible double selenation mechanism is shown in Scheme 2 and Scheme 3. The first step of the reaction involves the generation of the intermediate B via A by the Cu-mediated electrophilic substitution of 1 with selenium. The oxidative homocoupling of the intermediate B then proceeds to give

• -position to form the intermediate C and the selenide anion F. The intermediate C undergoes a reductive elimination and aromatization to give the selenide 3 and Cu(I). Moreover, the Cu-mediated electrophilic addition of 3 and selenium affords G, which aromatizes to form E and then probably undergoes a

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

• affecting the newly introduced fluorine atom was attempted by a two-step, one-pot protocol involving an in situ esterification of a highly electrophilic pyridinium triflate intermediate [77] and afforded the anti-β-fluoro-α-amino acid methyl ester 160a in 52% yield and with 98.8% ee (Scheme 39). On the

• other hand, when the quinoline-based ligand 162 was used, it was shown to promote the palladium-catalyzed direct electrophilic fluorination of β-methylene C(sp3)–H bonds. Thus, fluorinations of ʟ-phenylalanine 4-trifluoromethylphenylamides 161a–l carrying a range of functional groups such as fluoro

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• wide variety of substrates including silyl enol ethers, heteroaromatics and alkynes using an electrophilic CF3+ source (8 or 9), opening new opportunities to access pharmaceutically relevant trifluoromethylated products under mild reaction conditions. The ligand-based SET step involved the

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

• significant pharmaceutical use, the unsaturated analogs, cyclobutenes, are characterized by a poor reactivity of the π-bond, restricting the access to chiral cyclobutanes. This research group worked on a photocatalyzed addition of an electrophilic sulfonyl radical and a cyanide group across the π-bond of a

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

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

• makes a hydrogen bond interaction with the NH of the 5-methoxyindole (1a) and form the adduct B. This interaction assists 1a reacting with an electrophilic ketone (2a) to form the intermediate D via C–C bond formation (C). Re-aromatization of D generates E, which then protonates to form the desired

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

• -derived benzylic copper species with an electrophilic source of a cyano residue, Yang and co-workers reported on the Cu-catalyzed borylation of styrenes bearing an allylic group at the 1-position. After the initial addition, a cascade of reactions occurred, including cyanation generating a dearomatized

• steps: first, borocupration followed by an electrophilic cyanation, and finally, a second borocupration. It was discovered that steric factors determine the site of the first borocupration, while electronic effects are dominant in the second addition of boron (Scheme 61) [114]. The selective

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• electrophilic trifluoromethylthiolation with CF3SSCF3 [48][49] to furnish the bis(trifluoromethylthiolated) product 2. Conclusion We have reported the cascade trifluoromethylthiolation and cyclization reactions for the preparation of novel and potentially useful SCF3-containing pyrrolo[1,2-a]indol-3-ones

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

• )-catalyzed direct C–H borylation [22][23][24][25] gives 2,5,8,11-tetraborylated perylene [26]. The regioselectivity of the perylene borylation is determined by the steric factors rather than by the electron distribution in the arene and this regioselectivity complements that of electrophilic substitutions

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• Feringa recently reported a catalytic method for the synthesis of mixed alkyl aryl phosphonates based on a copper-catalyzed arylation of phosphonates with diaryliodonium salts [32]. Encouraged by this work, in the context of an electrophilic alkenylation of phosphonates, we reasoned that the action of a

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

• BODIPY core has not yet been achieved. Inspired by the works of Waser and co-workers showing the gold(I)-catalyzed C–H electrophilic alkynylation of various heterocycles (e.g., pyrroles, indoles, etc.) with ethynylbenziodoxolone (EBX) as an activated ethynyl synthon [38][39][40][41][42], we investigated

• the synthesis of ethynyl-substituted BODIPY derivatives 3–6 by gold(I)-catalyzed direct C–H functionalization (Figure 1c). By taking advantage of the reactivity of β-(2 and 6)-positions of BODIPY (1), which are susceptible to electrophilic reactions, β,β'-diethynyl-substituted BODIPYs 5 and 6 were

• core compared with 1a (Scheme 2). Under milder conditions, the yield of the β,β'-diethynylated product 6b was indeed improved to be 19% (from 2% of 6a). These results indicate that electron-rich substrates facilitate the direct electrophilic alkynylation of the BODIPY core. The structures of the series

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

• Pd(II) species to more electrophilic high-valent cationic Pd(IV). In addition, this protocol is not compatible with other PAHs except naphthalene, such as phenanthrene, pyrene and fluoranthene, and cannot tolerate some special functional groups, such as alkenyl and alkynyl groups. As a component part

• reaction and referring to previous research results [30][31][32], a Cu(I)/Cu(III) catalytic cycle was proposed (Scheme 4). First, Cu(I) is formed by the reduction or disproportionation of Cu(II). Then, aryliodonium salt oxidizes Cu(I) to highly electrophilic Cu(III)–aryl intermediate I. The coordination of

Synthesis of triphenylene-fused phosphole oxides via C–H functionalizations

• Md. Shafiqur Rahman and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2020, 16, 524–529, doi:10.3762/bjoc.16.48

• π-extension through a Suzuki–Miyaura coupling, Sonogashira coupling, and electrophilic alkyne carbocyclization [18]. Given the successful synthesis of the angularly fused phosphahelicenes, we became interested in the further exploitation of 7-hydroxybenzo[b]phosphole as an intermediate for the

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

• -thiaselenole; nucleophilic addition; nucleophilic substitution; rearrangement; seleniranium intermediate; Introduction The regio- and stereoselective synthesis of organoselenium compounds based on selenium-centered electrophilic reagents has been one of the most important and effective directions in

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• emtricitabine [30] (ingredient of Truvada®) and capecitabine [31] (Xeloda®) (see Figure 1) [32][33]. While the introduction of fluorine into preexisting heterocycles can require difficult-to-handle, expensive and highly corrosive electrophilic fluorine species [16][34][35], the present approach employs a

• were well tolerated, providing the corresponding fluorinated aminoalkylpyrimidines (10d–f) in yields of 81–93%. In spite of its potential electrophilic reactivity, the chloromethyl derivative 10g was obtained in excellent yield (90%) and could be used for further modifications to construct more complex

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• /iodoarene direct arylation method reported by Larrosa is notable: proceeding in high yields, at room temperature, and with no reported regioselectivity issues (Scheme 1) [12]. This system is hypothesized to proceed under mild conditions due to a highly electrophilic Pd catalyst generated in situ. In this

• proposed mechanisms for direct arylation (Scheme 2). Amongst these mechanisms, the most widely accepted is the concerted metalation–deprotonation (CMD) pathway [21]. Within the indole direct-arylation literature, however, there remains much discussion of an electrophilic metalation mechanism, with the

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• occurs selectively on the end opposite to the phosphorus donor atom [48]. This is because the position trans to the heteroatom, with greater π-acceptor character, is more electrophilic than the one opposite the σ-donor atom [9]. One can modify this electronic imbalance by attaching vicinal heteroatoms

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• yields, as can be seen in Scheme 12 [35]. Due to the limitations of ClSeCF3 as an electrophilic reagent for trifluoromethylselenolations in cross-coupling reactions, our group developed a new bench-stable reagent, namely trifluoromethyltolueneselenosulfonate (TsSeCF3) [36

• already demonstrated its versatility in numerous processes. Nevertheless, its use in oxidative cross-coupling reactions requires stoichiometric amounts of the oxidant, which limits the attractiveness of the method in some cases. Finally, the newly developed electrophilic reagent TsSeCF3 also demonstrated

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• Classically, benzonitrile was synthesized via Sandmeyer reaction, Rh/Co catalytic systems, or electrophilic reactions, and such reactions suffered from poor site selectivity. Therefore, utilizing the versatility of cyanoarenes, recently, Nicewicz and his team reported the preparation of cyanated products

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• OH group, facilitated proton transfer from the γ- to β-carbon atom via a process similar to the elimination/electrophilic addition to alkenes pathway. The computational results discussed above showed that the crucial point for sulfur atom migration was the formation of a tertiary carbocation at the β

Halogen-bonding-induced diverse aggregation of 4,5-diiodo-1,2,3-triazolium salts with different anions

• Xingyu Xu,
• Shiqing Huang,
• Zengyu Zhang,
• Lei Cao and
• Xiaoyu Yan

Beilstein J. Org. Chem. 2020, 16, 78–87, doi:10.3762/bjoc.16.10

• noncovalent interaction between electrophilic halides and Lewis bases or electron-rich regions [1][2]. Computational studies [3][4][5][6][7] and cyrstal architectures including XB-donors (σ-hole) such as perfluorocarbons [8][9][10][11][12], tetraiodoethylene [13], 1,2-diiodo-1,2-difluoroethene [14

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• electrophilic cyclizations to generate intermediate A. Intermediate A undergoes a 1,5-hydride shift, forming intermediate B. A subsequent cyclization forms intermediate C. Intermediate C generates intermediate E via one of two possible pathways: either a direct 1,3-hydride shift or an indirect pathway involving

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• during evolution. In contrast, the underlying mechanistic logic of terpene biosynthesis is based on repetitive electrophilic and nucleophilic functionalities in each oligomeric substrate, similar to nonmodular type II PKSs, coupled with conformational flexibility for enzyme-mediated juxtaposition of

• assist in refining our understanding of bacterial terpenoid biosynthesis. Examples of bioactive terpenoids. Repetitive electrophilic and nucleophilic functionalities in terpene and type II PKS-derived polyketide biosynthesis. a) Schematic representation. b) Type II PKS-derived polyketide biosynthesis. c