Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• [4][5][6][7][8][9][10], the RCM reaction constitutes a powerful tool to construct rings of various sizes. In 2009, Vanderwal and Dowling extended this process to the use of allylsilane derivatives which can be further submitted to an electrophilic desilylation reaction [51][52][53][54] giving an

• electrophilic desilylation agents which can be used, a large diversity of compounds can be accessible through this method [51][52]. Oxidation followed by desilylation with fluoride source produces the natural product poitediol (118) in overall good yield. 2 Nozaki–Hiyama–Kishi (NHK) cyclization The Nozaki

• associated to ring closure. To reach this goal, they first dedicated efforts in optimal syntheses of an electrophilic enimide 151 [73] and its conjunctive reagent, the neopentyl iodide 153. Both fragments were then engaged in a two-fold neopentylic fragment coupling, giving a bicyclic intermediate which

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• transformations of aryl substrates have also been reported for thiovinyl ethers, and also for dihydrodithiins (Scheme 5), although there are obvious limitations to this point of view. Classical electrophilic aromatic substitution procedures such as the Vilsmeier–Haack reaction or a simple nitration have been

• reported for vinyl sulfides, including dihydrodithiin 13 (Scheme 5a) [36]. In fact, Parham has found that fully unsaturated dithiins can undergo this electrophilic formylation, but at the same time also undergo a ring contraction and an aromatizing desulfurization to yield thiophenes as the main formylated

• products (viz 16, Scheme 5b) [37]. Electrophilic aromatic substitution under less forcing reaction conditions of the same substrate 15, using a room temperature nitration procedure, does yield the expected mononitrated dithiin 17 in good yield, without desulfurization [38]. 1,4-Dithiin-2-carbaldehyde (18

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• -established reagents for synthetic chemists. They are portrayed as an alternative to otherwise hazardous transition metals. This is due to their great reactivity in electrophilic group transfers [1][2][3][4], photo- or organocatalysis [5][6][7][8][9][10][11][12][13][14][15], and their utility as building

• blocks for the synthesis of natural products [16][17][18][19][20][21]. One subclass of HVIs is diaryliodonium salts (DIS), which have been used as versatile electrophilic arylation reagents in metal-catalyzed and metal-free reactions [22][23]. The corresponding cyclic diaryliodonium salts (CDIS) have

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• play an important role in redox-neutral asymmetric organocatalysis by forming nucleophilic enamine intermediates or electrophilic iminium cations. The same principles are used in oxidative transformations, where an amine can play the role of chirality source and the activator of substrate for oxidation

• (Scheme 2). In the enamine type of catalysis (Scheme 2A) the key enamine intermediate can undergo one-electron oxidation (route 1), electrophilic radical attack (route 2), or electrophile attack (route 3). The one-electron oxidation leads to the electrophilic cation radical which can further undergo

• addition to the electron-rich C=C bond [58] or proton loss followed by β-functionalization [59][60][61]. The iminium cation catalysis is used in the activation of electrophilic properties of enones for the nucleophilic epoxidation by hydroperoxides (Scheme 2B). N-Heterocyclic carbene (NHC) organocatalysis

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• -stereogenic center, which bears a methyl group, the electrophilic site (the iminium ion), and two possible nucleophilic sites (a prenyl group and a trisubstituted alkene within a cyclohexene ring). In conformer 12a, the prenyl group occupies a pseudo-axial position, the methyl group occupies a pseudo

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• reaction. However, in this reaction process, 2.0 equiv of CH-acids were needed against arylglyoxals since the electrophilic character of glyoxals is higher than that of aldehydes, generating less stable enones while reacting with CH-acids. First, 1.0 equiv CH-acid was reacted with 1.0 equiv arylglyoxal to

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• involved a highly reactive difluoroethylene intermediate, which was produced by the reaction between halothane and KOH. Keywords: aryl 1-monofluorovinyl ether; electrophilic 1,1-difluoroethene; halothane; multi-halogenated alkene; phenol; Introduction 2-Bromo-2-chloro-1,1,1-trifluoroethane (halothane

• , respectively), which are susceptible to basic conditions, were tolerated in the reaction, but ortho substituents hindered the reaction to some extent (Table 2, entries 9 and 10). 2-Hydroxychalcone (3l), which has an electrophilic enone structure, was also tolerated. The Michael addition product was not

• mechanism shown in Scheme 2 [15][26]. In the reaction medium, 3 is deprotonated by KOH to generate phenoxide ion 4, which acts as a base and as a nucleophile. Removal of an acidic hydrogen from halothane provides 5, which is a key intermediate in the reaction. Intermediate 5 is sufficiently electrophilic to

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• formal [4 + 1] cycloaddition (Scheme 1). Results and Discussion FPDs are highly reactive compounds [25][26] containing an highly electrophilic enone fragment which facilitates the course of cycloaddition and nucleophilic addition reactions. In recent years, some types of cycloaddition reactions were

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• synthesized from 2-aminobiphenyl according to the literature [47]. Subsequent reaction with phosphorus trichloride and electrophilic aromatic substitution gave a chlorophosphine intermediate, which was directly reacted with (S)-1-phenylethylamine, then hydrogen peroxide. Phosphonamide diastereoisomers 17 were

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• functionalized through the addition of electrophilic reagents, various functional arms can be attached. Moreover, N-TAAD derivatives were expected to be less prone to cage-opening reaction compared to 3O-TAADs. Here, we wish to report the synthesis of TAADs decorated with N-amino(amido) groups (3N-TAADs) by

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• due to the strong electron-withdrawing effect of bromine, enhancing the electrophilic property of bromo-substituted salicylaldehyde. Because of the poor solubility in the eluent, the yield of dichloro-containing 1c (88%) was lower than 1a after isolating by column chromatography. This was also found

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• accepted. Evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose suggests that the ligand can bind to GMD, but that targeting inhibitive S-alkylation of an sp3-hybridised C6 electrophilic probe is ineffective here. a) Proposed oxidative pathway for provision of GDP-ManA 5 from GDP-Man 1, C6 stereochemistry of 3 is

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• compound 0. This nucleophilic and basic intermediate is prone to dehydration (step 6), leading to the strongly electrophilic and oxidising key intermediate G, which is commonly known as compound I (cpd I). Although there has been a lot of debate regarding the exact structure and electronic properties of

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• electrophilic substrates (Figure 2). The HOMO orbital is distributed over the purine ring with the largest amplitude on the N7 atom, which designates this position as the most nucleophilic in 1. The second most populated site is the N6 atom, which appears as more nucleophilic than N9 atom. To facilitate a

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• on the SiMe(OSiMe3)2 unit, which were readily converted through Pd- or Cu-catalyzed electrophilic substitution reactions into an array of furfurals decorated at C3 with carbon- or heteroatom-containing substituents (Scheme 1). Conversely, all of our subsequent efforts to achieve cross-coupling

• activation [19]. Thereby, C3-triorganosilyl-substituted furfurals could be suitable platforms to develop a two-step modular approach to 3-substituted 2-furyl carbinols, entailing nucleophilic addition to the aldehyde function and oxygen-assisted electrophilic substitution of the C–Si bond (Scheme 1). Results

• ). With the 3-silylated 2-furyl carbinol substrates at hand, we then considered C–Si bond activation strategies relying on the assistance of the oxygen atom to promote electrophilic substitution reactions with carbon electrophiles. C3–Si bond functionalization through intramolecular activation by

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• intermediates in the total synthesis of natural products utilizing their electrophilic keto group as reactive site. Suitable key reactions are, e.g., aldol additions, carbonyl ene reactions, Mannich reactions, and additions of organometallic reagents. The vicinal arrangement of carbonyl groups allows the

• bearing an electrophilic keto group as reactive site. The vicinal arrangement of carbonyl groups allows the stabilization of reactive conformations by chelation or dipole control. Suitable key reactions are e.g., aldol additions, carbonyl ene reactions, Mannich reactions, and additions of organometallic

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• which their observed relative dienophilic reactivities could be rationalized. Besides, the Fukui functions of the carbon/nitrogen and phosphorus atoms of the >C=P– and –N=P– functionalities were also computed which revealed their hard electrophilic character and accorded well with the dienophilic

• calculate various reactivity descriptors, such as electrochemical potential, electrophilicity and nucleophilicity indices, global hardness, electronegativity, etc. The concept of hard–soft acid–base (HSAB) was used to explain the reactivity of the organic molecules towards electrophilic and nucleophilic

• reagents [19]. Thus a quantitative descriptor, the Fukui function was defined as for nucleophilic attack and for electrophilic attack, where ρN+1(r), ρN(r), and ρN−1(r) are the electron densities at a point r in the system with N+1, N, and N−1 electrons, respectively, all with the ground-state geometry

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• containing an unsubstituted cyclopropane ring (1) or bearing Me (2) and COOMe (3) groups were obtained using previously reported protocols [15][19]. Complex 4 is new. Compound 4 was obtained by the reaction of an electrophilic dehydroalanine complex with a bromomalonate anion (Scheme 1). The reaction

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• addition, radical cation addition, and electrophilic aromatic addition, have also been proposed [1][10][29]. A proposed mechanism is depicted in Scheme 2: First, the hydroxy group on the A- or B-ring is converted into a radical by a P450-induced single-electron transformation. The resulting radical then

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• , the optimal reaction conditions for the electrophilic monobromination was set as to grind the substrates (1 mmol) in an automated grinder with 1.1 mmol of NBS at 100 rpm in PEG-400 (0.2 mL per mmol of the substrate) as a grinding auxiliary. We next explored the substrate scope of the catalyst-free

• observed for 4-phenylphenol indicating this electrophilic halogenation is selective to electron-rich aromatic rings only (product 2f, Scheme 3). Also, aromatic halogenation prevails over α-halogenation of a ketomethyl group as was demonstrated by the formation of product 2m as the sole product for the

• just 2 min of grinding (products 2q and 2r, Scheme 3). Next, a series of aniline derivatives were taken as the substrates for this electrophilic bromination by NBS. To our delight, the corresponding bromo derivatives were formed in high yields (75–89%) within 5–15 min of grinding (products 2s–y, Scheme

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• atom is reversed (umpolung) from electrophilic to nucleophilic (Scheme 3). This approach can be exploited in many organic reactions, such as: the benzoin condensation [16][17], esterification and amidation of benzaldehydes and cinnamaldehydes [18][19], synthesis of γ-butyrolactones [20], synthesis of

• [33]. Flow electrochemistry was applied to oxidize the Breslow intermediate to the corresponding electrophilic acylthiazolium intermediate, which then functioned as an acyl-transfer reagent, reacting with alcohols or amines. To the best of our knowledge, only one research group reported the cathodic

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• amine) on the most electrophilic component of the α-ketoaldehyde (its aldehyde) to give intermediate 5. However, the ensuing cyclization (via a hydration of its imine bond to allow for a rotation) would then lead to compound 4 which is rarely the major reaction product. Since compound 3 is the main

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• , it was observed that the MBH reaction of 6b with acrylonitrile A resulted in the formation of product 8bA which evidenced that 6b underwent Morita–Baylis–Hillman reaction at the electrophilic carbonyl center as well as Michael addition reaction at the nucleophilic nitrogen center (N-9). Similar

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• intramolecular nucleophilic dearomatization and protonation or electrophilic alkylation reactions, affording the corresponding dihydronaphthylene-fused γ-phosphinolactams 135–142. Methanol was used as the electrophile for protonation, while methyl iodide and allyl bromide were used as electrophiles for

• proceed due to their reduced nucleophilicities, generating the corresponding phosphonamidates only through the reaction with the more electrophilic phosphonochloridate (Scheme 32) [57]. [4 + 1] Annulation via formations of both C–P and P–N bonds (1S,3R)-2-(tert-Butyldiphenylsilyl)-3-methyl-1-phenyl-2,3

• ortho-directed lithiation with tert-butyllithium with carbamate as the directing group followed by electrophilic quench with methyl chloroformate and intramolecular aminolysis. Finally, hydrolysis removed the directing group, affording the final product 239 in 50% yield (Scheme 38) [59]. Structurally

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• olefins in moderate yields [5]. Prakash et al. also achieved fluoride-induced nucleophilic (phenylthio)difluoromethylation of carbonyl compounds using PhSCF2SiMe3 [6]. Quite recently, Shen et al., developed various nucleophilic, electrophilic, and radical difluoromethylthiolating reagents [1]. However