CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• , such as reductions, eliminations, as well as C–O, C–N, or C–C bond formations (Scheme 31). α-(Trifluoromethyl)propargylium has also been suggested as an intermediate in superacid-mediated Friedel–Crafts reactions [86]. When [α-(trifluoromethyl)propargyl]allyl silyl ether 120 was added to a

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• bond opposite to the fluorine atom. A consequence of this is the tendency of fluorocyclopropanes, and in particular gem-difluorocyclopropanes, to undergo various transformations initiated by a homolytic C–C bond breaking. Thermal stereomutation: In 1975, Staricco and co-workers described the thermal

• the activation energies for both cis–trans-isomerization and for the transformation of vinylcyclopropanes into cyclopentenes. Both processes could occur by a C–C-bond homolysis to form a diradical. Computational studies by Gety, Hrovat, and Borden indicated that there would be a preference for

• -difluoro-1-alkenylcyclopropanes 90–92 (Scheme 41) [88]. All three compounds underwent a highly regioselective cleavage of the C1–C3 bond. Hence, the major products of all rearrangements were produced via [1,3]-sigmatropic shifts (Scheme 41). The products were the result of the breaking of the C–C bond

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• tautomers was possible, revealing them as significant intermediates for the mechanism elucidation. Keywords: α-alkylthio esters; α-alkylthio ketones; Bunte salts; C–C bond cleavage; β-keto esters; Introduction During the last ten years, sodium S-organyl sulfurothioates, also known as Bunte salts, were

• , and related compounds. Some of them are catalyzed by expensive transition metals, such as gold, iridium, palladium, and titanium. More recently, the selective formation of C–S bonds using 1,3-dicarbonyl compounds, followed by a C–C bond cleavage has emerged as a versatile and less expensive protocol

• ). However, when compound 5 reacted with sodium S-benzyl sulfurothioate (2a), the enol product 6 was obtained in 86% yield after 2 h at 100 °C. In this case even a longer reaction time and a higher temperature were not effective to achieve the C–C bond cleavage. This interesting result also gave us the

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• formal synthesis of inthomycin C ((−)-3). In 2018, Donohoe et al. demonstrated a tin-free, short and efficient total synthesis of inthomycin C ((−)-3) by comprising the three key steps of C−C bond-forming reactions: i) a vinylogous Mukaiyama aldol reaction, ii) an olefin cross-metathesis reaction, and

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• ]. It is well-known that the inner helix and outer helix C–C bonds of helicenes differ in their length [9]. Deviations of some of them from the standard aromatic C–C bond of benzene (1.393 Å) are significant. The length of the inner helix C–C bonds of [6]helicene 12 varies from 1.400 to 1.459 Å. On the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• cation, which is intercepted by the titanium enolate and results in the new C–C bond formation to give the five-membered carbocycle 169. Conclusion The all-carbon [3 + 2] cycloaddition, together with the [3 + 2] annulation, continue to be an attractive class of reactions for the synthesis of highly

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• originating from the isopropyl group C20–19–21 or, by involving multiple C–C bond cleavages and hydrogen rearrangements, from the C25–3–4 portion. Alternatively, a combined loss of the C8–9 moiety and one methyl group (C22, C23, C24, or C25) is possible which basically combines the fragmentations of Scheme 1A

• q2•+, followed by two more α-fragmentations to r2•+ (Scheme 4B). A final α-cleavage then yields the target ion s2+. The generation of the base peak ion at m/z = 120 from the C25–3–4–5–6–10(–9)–11–23 moiety of 2 is more difficult to understand, as it must proceed with four C–C bond cleavages

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• )-T5a,b, followed by the transfer of a methyl group to a nearby nucleophile (for example, F− or the succinimidate anion). We assumed that changing the arrangement of the ester groups from endo to exo (increasing the distance between the C=C bond and the carbonyl oxygen atom) would render an

• under halofluorination conditions. We expected that the imide moiety of this molecule would fix the carbonyl oxygen atom in a position remote to the C=C bond to avoid cyclization. Indeed, the bromofluorination of tricyclic 19 was successful. However, the process required repeated reagent addition and

• isomeric halofluorination products can be explained by the preferred formation of the halonium ions T6a–c, respectively, since the halogen cation attacks the C=C bond of the imide 19 from the less hindered side, followed by rearrangement into the intermediates (rac)-T7a–c, respectively. For epoxides and

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• and aldehyde–amine–alkyne (A3) coupling reactions [16]. Off this discovery, in this letter, we further expand the scope of using both ChNCs and ChsNCs as a catalyst support for Pd NPs to allow access towards other highly relevant C–C bond-forming reactions. A one-pot fabrication method is used to

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• (see computational details section for a full description). Compounds 7, 9, and 10 have the dependence of the molecular dipole moment μ with the rotation around the C–C bond. The correlation plots between the experimental log P of compounds 1–11 and a) dipole moment and b) predicted log P are shown in

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• –carbon (C–C) bond-forming reactions play a key role in organic chemistry. Hereby the stereoselectivity of the reaction is highly important due to the different behavior of stereoisomers in human metabolism [1][2]. Stereocontrol was achieved either via an auxiliary [3][4][5][6][7] or a catalyst [8], both

• providing the stereoinformation necessary for induction during the C–C bond formation. Catalytic approaches for C–C bond-forming reactions even found their way into the relatively young field of supramolecular chemistry, e.g., regioselective Diels–Alder reactions within supramolecular hosts as described by

• processes based on the principle to use self-assembled coordination platforms (or as in the present case mixtures thereof) to control stereoselective C–C bond-forming reactions. Stereoinduction usually relies on spatial proximity of the prochiral carbon atoms and a chiral information of, e.g., a chiral

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• 74 into the stable derivatives 75 having a strong C–C bond through the nucleophilic substitution reaction with phenol and anisole in the presence of trifluoromethanesulfonic acid (TfOH) with total stereoinversion. This suggests that the nucleophile attacks occur from the concave face of the π-bowl

• C–C bond (1.54 Å). Due to this, triazasumanene hold high strain energy, hence difficulty in its synthesis and also high reactivity of nitrogen present in it. To date, in most of the heterosumanene substitution has been reported at the benzylic positions except in the case of triazasumanene. In this

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• ][119][120][121][122]. There are many approaches to photosensitized fluorination that do not involve direct C–H activation, which are reviewed elsewhere [123][124][125], such as C–C bond fragmentation/C–F bond formation [126], aminofluorination of cyclopropanes [127] and decarboxylative fluorination

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• cases, for the same fluorination motif, the cyclopropane derivatives have a lower lipophilicity compared to their acyclic equivalents. It is also useful to compare lipophilicities of acyclic and cyclopropane derivatives in which the isosterism represents conversion of a C–H and C–F bond into a C–C bond

• , cyclopropyl, and 3-oxetanyl substituents by fluorination level (exchange two C–H bonds by a C–C bond or C–O–C bonds, same carbon count). Comparison of lipophilicities between isopropyl and cyclopropyl substituents grouped by exchange of C–H/C–F bonds by a C–C bond (same carbon count). Organised by the

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• metal-complexes-catalyzed [23][24][25][26] or organocatalyzed [27][28][29][30][31][32] Michael reaction is one of the most important synthetic tools for the asymmetric formation of a C–C bond. Moreover, the generation of the first stereocenter of a given configuration during the catalytic process leads

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• under metal-free conditions and uses cheap K2S2O8 as oxidant with easy handling and a broad substrate scope. The reaction proceeds through a radical phosphinoylation–cyclization via a tandem C–P and C–C-bond formation. Biologically active compounds featuring the chroman-4-one framework. X-ray structure

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• conformational changes [11][12][13]. For the latter, nucleoside analogues (Figure 2, VI) containing a trans-butenyl moiety where the endocyclic C–O bond was replaced by a C=C bond are recognized by kinases as dUMP surrogate (V) [11]. However, there is no existing data for the corresponding fluoroalkene (VII), as

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

• oxidants and/or additives. In order to provide a solution towards these limitations of the undirected C–H activation, the group of Lee initiated a project merging gold-catalyzed C–H activation with photoredox catalysis (Figure 42) [104]. Such a dual catalytic system should promote the desired C–C bond

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• -oxide (TMANO), and dimethyl sulfoxide (DMSO). Once a new coordination vacancy has been opened on one of the cobalt centers, coordination of the olefin sets the stage for the subsequent C–C bond forming steps. The olefin is inserted into the less hindered Co–C bond, determining both the regio- and

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• formed by an intramolecular C–C or C–N bond-formation event, as detailed in the following. 2.1 Synthesis of phenanthridines via photocatalyzed intramolecular C–C bond formation A typical approach makes use of imidoyl radicals [30][44] as the key intermediates. Among the different methods proposed to

Recent synthesis of thietanes

• Jiaxi Xu

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

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

• reactions of oxime radicals. These reactions are classified into cyclizations involving C–H bond cleavage and cyclizations involving a double C=C bond cleavage. Keywords: iminoxyl radicals; isoxazolines; oxidative cyclization; oxime radicals; oximes; Introduction Free radicals in which an unpaired

• -system. According to EPR data, the authors suggested that iminoxyl radicals 101 generated from oximes 100 by photolysis with the addition of the di-tert-butyl peroxide gave nitroxides 102 [123]. The widespread use of iminoxyl radicals in organic synthesis involving a radical addition to a C=C bond

• carried out under the action of a PC-I/TEMPO catalytic system and the irradiation of blue LEDs (Scheme 37) [127]. A variety of electronically rich and electronically poor aryl or heteroaryl groups at the oxime group (R1) are well-tolerated (products 115a–e). Oximes with disubstituted double C=C bond also

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

• , the ability of transition metal complexes to intercept alkyl radicals has been exploited for expanding the possibility of C–C bond formation reactions to cross-couplings. In all of these transformations, the substituents on the alkyl radical determine if it reacts as a nucleophile or an electrophile

Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules

• Shigeyuki Yamada,
• Takuya Higashida,
• Yizhou Wang,
• Masato Morita,
• Takuya Hosokai,
• Kaveendra Maduwantha,
• Kaveenga Rasika Koswattage and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 1154–1162, doi:10.3762/bjoc.16.102

• (Figure 2A), which show prominent fluorescence not only in dilute solution, but also in the crystalline state [27][28][29][30][31]. As a powerful tool to develop novel pure organic phosphorescent molecules, we envisioned the structural modification of the carbon–carbon triple (C≡C) bond in fluorinated

• proposed mechanism of Pd(II)-catalyzed C≡C oxidation is illustrated in Scheme 2 [33]: The catalytic cycle starts with the coordination of the electron-rich C≡C bond to the electron-deficient divalent Pd center, forming the corresponding π-complex (Int-A). Int-A smoothly undergoes nucleophilic attack by the

• proposed reaction mechanism, the successful isolation of the half-oxidized benzil derivatives 2a and 2b from the oxidation of fluorinated bistolanes 1a and 1b, respectively, may be due to the decreased reactivity of the C≡C bond toward Pd(II)-catalyzed C≡C oxidation caused by the adjacent electron

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• that steric hindrance plays a role during the reaction. Oxazolones 2a–j contain two exocyclic C=C bonds in their skeleton and these can, in principle, have different conformations. The NMR characterization of 2a–j showed that they are obtained as single isomers. The oxazolone exocyclic C=C bond has the

• (Z)-configuration, because the signal assigned to the C=O group appears as a doublet in the proton-coupled 13C NMR spectrum, with a 3JCH coupling constant of 5.6 Hz [50]. In contrast, the C=C bond of the styryl group has an (E)-configuration, as inferred from the observation of a 3JHH coupling

• constant of 16 Hz between the two olefinic protons of the styryl fragment. Further characterization of the new oxazolones was provided by the determination of the crystal structure of oxazolone 2c. A molecular drawing of 2c is shown in Figure 4, where the (Z)-configuration of the exocyclic C=C bond (C7–C8