C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• Information File 1) [75]. Different reagents for the bromination or chlorination were also evaluated (Table 1, entries 1–3) and NBS was the most efficient one (Table 1, entry 1). With the best reaction conditions in hand, the nature of the hydrazone part was first investigated (Scheme 2). Under standard

• conducted in the presence of 1a in a THF/MeCN mixture (1:1) [75], but no product was detected (Scheme 4D). Based on these experiments and literature data [66], a two-step one-pot process was suggested based on 1) the bromination of the hydrazone 1 followed by 2) the anion metathesis in the presence of

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• be developed by considering active structures. This was demonstrated by Crawford et al. [86] in their investigation of a peptide-catalysed atroposelective bromination (Figure 5). The authors found that the peptidic catalysts can broadly be defined in two categories of β-turns: a type I’ pre-helical

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• for our needs [52][53]. Benzylic bromination followed by nucleophilic substitution offers a general approach for the introduction of the nitrogen atom [54][55][56]. Consequently, the continuous flow Wohl–Ziegler bromination of 2b was attempted [57]. Even though we could observe excellent LCMS

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Avenida Francisco J. Múgica S/N 58030, Morelia, Michoacán, México 10.3762/bjoc.20.141 Abstract The reaction mechanism for the chlorination and bromination of 2-naphthol with PIDA or PIFA and AlX3 (X = Cl, Br), previously

• an equilibrium of Cl–I(Ph)–OTFA–AlCl3 and [Cl–I(Ph)][OTFA–AlCl3], rather than PhICl2 being the active species. On the other hand, bromination using PIDA and AlBr3 was more efficient, wherein the intermediate Br–I(Ph)–OAc–AlBr3 was formed as active brominating species. Similarly, PhIBr2 was higher in

• halogenation via PhIX2. Keywords: aromatic bromination; aromatic chlorination; density functional theory (DFT); hypervalent iodine; iodine(III); Introduction Hypervalent iodine(III) reagents have gained attention as strong oxidants with a low toxicity [1][2][3][4][5][6][7][8] and due to the ability to mimic

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• type haloalkenes. (b) Fate of unsymmetrical dialkyl ketones on direct bromination. (c) This work. Substrate scope. Unless otherwise stated 0.2 mmol of 1 was used and the isolated yields are given. Proposed catalytic cycle. Conditions screening (without oxidant)a. Conditions screening (with oxidant)a

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• -bromoaniline (1a) and ethyl trifluoroacetoacetate (2), adapting a known procedure from Schlosser and Marull (Scheme 1) [17]. The cyclization of 1a with 2a chemoselectively afforded 8-bromo-2-trifluoromethyl-4-quinolone (3) rather than 8-bromo-4-trifluoromethyl-2-quinolone. Bromination of 3 with phosphoryl

• bromination in position 3, followed by treatment of brominated intermediate 10 with phosphoryl bromide (Scheme 5) [34]. To our delight, the optimized conditions for the synthesis of alkynylated quinolines 6 could be applied also to the three-fold Sonogashira reaction of 11. However, the reaction time had to

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• be employed in two variants modulated by light irradiation. This external switch can be used to selectively trigger side-chain or core halogenation. Keywords: aryl halides; benzyl halides; bromination; sustainability; Introduction Activation through halogens has become a key strategy in achieving

• functionalisation on the aromatic ring when used in the dark [20]. A classic example is the bromination of toluene with molecular bromine. When the system is exposed to light (right side of Figure 1), a radical mechanism is initiated by Br• coming from Br2 homolysis. Propagation involves the reversible abstraction

• CCl4 to prevent undesired solvent degradation. Furthermore, the direct use of Br2, even if used in low concentration, exhibits limited selectivity towards benzylic bromination, primarily due to co-bromination occurring on the aromatic ring. This side process produces awkward halogenated byproducts that

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• obtained. Compounds 3a–j were subsequently transformed to 5a–t by Suzuki–Miyaura cross-coupling. The bromination of 1 was performed by using Br2 (1 equiv), Ac2O (1.5 equiv), AcOH (25 °C, 1 h) and yielded the desired product in 52% [62]. With the starting material in hand, initial Sonogashira–Hagihara cross

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• -workers reported a method for the selective bridge bromination of BCPs, giving access to brominated 1,2-BCP (±)-16 (Scheme 2) [33]. By exploiting the homolytic cleavage of the C–Br bond using in situ-generated silyl radicals, they were then able to harness the installed bromide functionality in

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• transformations. We started studying the reactivity of allene 11 with the bromination reaction. The reaction was carried out without a solvent at a reagent ratio of 1:1. Bromine was added dropwise to allene 11 at −30 °C and the reaction mixture was stirred at the same temperature until colorless. The bromination

• )-configuration of product 13 was determined by the absence of the F–F constant in the 19F NMR spectra. It should be noted that the bromination reaction could also be carried out in diethyl ether. In this case, the bromo derivative 13 could be isolated in pure form only after several distillations, which

• . In contrast to bromination, the reaction with ICl is less selective and leads to the formation of addition products at both double bonds. At the same time, the reaction proceeded predominantly at the terminal double bond with the formation of a mixture of isomers (Z)-14a and (E)-14b. The content of

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• corresponding bis(thiophenyl) thioether, which then underwent successive bromination and iodination to give intermediate 18. Next, a two-fold Suzuki–Miyaura cross-coupling occurring chemoselectively on the iodinated positions allowed the symmetric extension of the hydrocarbon scaffold, with the insertion of two

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• be more basic than diamine 1, the cumulative effect of all functional groups in this compound led to a slight drop in the pKa value compared to quinoquinolines 3 and 5, despite the presence of two electron-donating methoxy groups. Bromination and tele-elimination As preliminary experiments showed

• , dipyridoacenaphthene 5 is not brominated by molecular bromine in chloroform or acetic acid. The action of the NBS–DMF system, previously proposed for the electrophilic bromination of alkylaromatic compounds [26], leaves substrate 5 unchanged at room temperature, and when heated to 75 °C for several days causes its

• activator of NBS, as was previously shown by the example of a very successful bromination of 6-methylquinoline at position 5 with a preparative yield of 74% [27]. Indeed, under the new conditions, we obtained dibromo derivative 15 in high yield without heating and subsequent purification (Scheme 7). The

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• , China 10.3762/bjoc.20.14 Abstract An efficient and practical method for the synthesis of C5-brominated 8-aminoquinoline amides via a copper-promoted selective bromination of 8-aminoquinoline amides with alkyl bromides was developed. The reaction proceeds smoothly in dimethyl sulfoxide (DMSO) under air

• , employing activated and unactivated alkyl bromides as the halogenation reagents without additional external oxidants. This method features outstanding site selectivity, broad substrate scope, and excellent yields. Keywords: aminoquinolines; C–H bromination; copper catalysis; regioselectivity; Introduction

• , the synthesis of important C5-halogenated products gained particular attention since Stahl et al. reported the first chlorination example using LiCl as the halogen source [10]. Following this pioneering work, elegant strategies for the C5–H bromination of the quinoline ring employing simple inorganic

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• % yields. para-Amino- and boronic acid-substituted benzamides did not react. While meta-bromo-substituted benzamide gave 2j in 84% yield, ortho-bromination resulted in a diminished yield of 2k (55%). We obtained 3,5-disubstituted N-acyl carbazoles 2l and 2m in 91% and 88% yields. The same disubstitution

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• synthesis began with the generation of substituted 2-bromo-1-aminonaphthalenes 9 and 10 (Scheme 6). After α-bromination of tetralones 1 and 2, intermediates 3 and 4 underwent elimination/aromatization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford 2-bromo-1-naphthols 5 and 6 in fairly good yield

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• cyclization reaction using 4e by 1H NMR. Versatile reactivities of cyclopropanes 1a. Preparative methods for cyclopropanedicarboxylates 1a. Bromination of ethyl acetoacetate (3c) and reaction with nitrostyrene 2a. Reaction of 4b with (diacetoxyiodo)benzene (top); structural determination of product 9 (bottom

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• -dihydroisoquinolin-3(2H)-one (2a) that represents the homoanalogue of the parent 3-bromoxindole (1; R1, R5: H). The starting 1,4-dihydroisoquinolin-3(2H)-one was prepared from commercially available 2-indanone by Schmidt rearrangement with azoimide [28]. Unfortunately, its bromination using various agents (NBS

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• University, 25240 Erzurum, Turkey Department of Chemistry, Gebze Technical University, 41400, Gebze, Turkey Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey 10.3762/bjoc.19.56 Abstract Previously we reported on the bromination of endo-7-bromonorbornene at different

• erroneous mechanistic pathway. Keywords: bromination; computational NMR; γ-gauche effect; NMR; NOE-Diff experiments; Introduction Nuclear magnetic resonance (NMR) spectroscopy is one of the most important analytical tools used to determine the structure of organic compounds. NMR not only confirms the

• compound 6. Bromination of endo-7-bromonorbornene. Our mechanism suggested for the formation of 6 [4]. The mechanism suggested by Novitskiy and Kutateladze for the formation of 7 [3]. Supporting Information Supporting Information File 102: Double resonance spectra and X-ray crystal structure. Funding The

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• methyl ether aromatic substituents were tolerated. Unsymmetrical 10,11-dihydro-5H-dibenzo[b,f]azepine derivatives 71 have been synthesised by ortho-bromination of functionalised dihydrostilbenes 67, followed by intramolecular cyclisation using Buchwald–Hartwig amination (Scheme 14) [54]. The pathway

• relies on a double Sonogashira coupling [(i) and (iii)], reduction (iv), and bromination (v), followed by Buchwald–Hartwig amination (viii) (Scheme 14). While interesting, the reaction has limited substrate scope due to the reliance on a late-stage bromination. To achieve the correct ortho-bromo

• , prepared by benzylic bromination of the methyl substituents of 132 and 133 (Scheme 29). 5 1,4-Michael addition Narita et al. [72] reported their total synthesis of bauhinoxepine J (139), a quinone dihydrobenzoxepine derivative, by means of a base-promoted intramolecular etherification (Scheme 30). 6

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

• then brominated with an excess of bromination reagent, which effects the 1,2-sulfur-migratory ring expansion, followed by bromination-induced dehydrogenation to the aromatic ring [31]. At the time of writing this review, the resulting benzoannelated dithiane 5 is also commercially available in small

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• of Science, Port Said University, 42522-Port Said, Egypt 10.3762/bjoc.19.9 Abstract Cholesterol reacts under Appel conditions (CBr4/PPh3) to give 3,5-cholestadiene (elimination) and 3β-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates

• conversion of cholesterol 1 into diene 9, bromide 4, and azides 5 and 6. Manipulations for bromination and azidation of cholesterol. Supporting Information Supporting Information File 75: X-ray crystallography and NMR spectra. Supporting Information File 76: Crystallographic information files for compounds

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

• irradiation. The resulting iodoaryl cation radical abstracts the hydrogen atom from the benzylic position to form a benzyl radical, whose bromination gives the racemic benzyl bromide. The second step takes place without the participation of light and leads to only one enantiomer due to the assistance of the