Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• -protic nature make them suitable dissolving agents for a wide range of reagents. Furthermore, the polar bond C–X can be activated by different chemical procedures (metal or acid catalysis, for example) and serves as a reactive center. In this regard, dihalomethanes can act as halogen donors in

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• , Chiba 263-8522, Japan 10.3762/bjoc.21.43 Abstract β-Amino cyanoesters are important scaffolds because they can be transformed into useful chiral amines, amino acids, and amino alcohols. Halogen bonding, which can be formed between halogen atoms and electron-rich chemical species, is attractive because

• of its unique interaction in organic synthesis. Chiral halonium salts have been found to have strong halogen-bonding-donor abilities and work as powerful asymmetric catalysts. Recently, we have developed binaphthyl-based chiral halonium salts and applied them in several enantioselective reactions

• ; chiral halonium salt; contiguous stereocenters; halogen bonding; Mannich reaction; Introduction Halogen bonding (XB) has attracted intense research attention for its unique interaction between halogen atoms and electron-rich substituents [1]. XB has been applied to various fields of chemistry, such as

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• substitution. Substituents such as halogen atoms must be introduced into the N-acetyl diazocine structure during the synthesis of the building blocks. In the present work we start from mono- and dihalogenated N-acetyl diazocine 2–4 (Figure 2) and focus on the further derivatization via cross-coupling reactions

• diazocine attached to glutamate to form a photoswitchable neurotransmitter [10]. The halogen-substituted N-acetyl diazocines 2–4 were used as the starting compounds for further derivatization via Pd-catalyzed cross-coupling reactions. Solutions of the Z isomers are yellow. The E isomers are red. Synthesis

• reactions. Equivalents are normalized to the used amount of N-acetyl diazocine starting material. Derivatization of halogen-substituted N-acetyl diazocines via Suzuki–Miyaura reaction. Equivalents are normalized to the used amount of N-acetyl diazocine starting material. Derivatization of halogenated N

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• subjected to Appel conditions in DMF, using elemental iodine as the halogen source. Notably, we were not able to efficiently generate the corresponding bromides with the same strategy. The preQ1 derivative 3a was synthesized in a 2-step reaction sequence analogous to the DPQ1 derivative 4b, while four steps

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• ]. In addition, cyclic diaryl λ3-bromanes have been successfully employed as halogen-bonding organocatalysts in Michael addition [8] and their chiral variants were efficient in catalyzing enantioselective Mannich reactions of ketimines with cyanomethyl coumarins [9] and malonic esters [10]. These

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• potent. Interestingly, the presence of a halogen, preferably a bromine substituent at the para-position of the acetamide group increased the antibiotic potential against S. aureus. A comparative analysis of the antimicrobial data between mono/dialkylated derivatives revealed that O-alkylation did not

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• hydrogen-atom-transfer mechanisms with a Hantzsch ester 34 as presented in Scheme 12. Moreover, the study has explored the impact of substrate steric hindrance and halogen bond strength on catalytic efficiency, revealing that bromo- and iodo-substrates react more efficiently, while chloro-substrates

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• substituted with halogen atoms (–F, –Cl, –Br) were also suitable for this transformation, efficiently giving the desired products in yields of 65–80% (3b, 3e–g), thus facilitating further functionalization possibilities. Notably, substrates with substituents at the sterically hindered 7-position of the

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• simultaneously between E and the arylboronic acids 2, leading to the formation of G (Scheme 5, path c). The intermediates G then undergo reductive elimination to yield 3. To assess the impact of halogen substituents, we also examined reactions of 2-halogenated benzofurans 1a-X (1a-Cl: X = Cl; 1a-Br: X = Br; 1a-I

• nickelacyclopropane Eb in a stoichiometric reaction. Screening of conditions for coupling of 1b with 2b. Effect of halogen substituents. Supporting Information Supporting Information File 82: Detailed experimental procedures and spectral data. Acknowledgements This work was partially performed using facilities of

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• conditions were compatible with many substrates containing methyl, methoxy, halogen, and aryl groups, providing excellent enantioselectivies and moderate to high yields. Control experiments indicated an activation mode through the vinylidene ortho-quinone methide (VQM) intermediate as well as the importance

• in the formation of axially chiral products 191 (Scheme 56) [86]. The authors achieved good results in terms of enantioselectivities and yields with mostly methyl, methoxy, or halogen modifications in various positions. The configurational stability experiments of products 191 confirmed stable

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• test the potential effects on halogenated aromatic structures and no dehalogenation was detected up to 24 hours stirring. The retention of halogen atoms on aryl halides distinguishes this procedure from traditional techniques, such as those involving LiAlH4, which can cause dehalogenation [30][31]. The

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• two steps from 1,8-DHN (19) [57]. Methoxymethyl (MOM) protection of free -OH group of 29 using NaH and MOMCl afforded MOM-protected naphthol 30 in excellent yield (96%) [58][59]. It is worth highlighting the structural differences of naphthalenes 25 and 30, where the halogen (iodine) is on the same

• ring with the -OMe group on 25, while the halogen (bromine) is on the opposite ring with the -OMe group on naphthalene 30. This small yet important difference allowed us to synthesize benzo[j]fluoranthenes 23 and 28 selectively with free -OH groups at different positions. Bromonaphthalene 30 was

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• building blocks like organohalides can be converted into alkyl radicals by means of photoinduced silane-mediated halogen-atom transfer (XAT) to offer a mild and straightforward methodology of alkylation. In this research, we present a metal-free strategy for the photochemical alkylation of dehydroalanine

• radical activation, resulting in milder and safer reaction conditions [14][15][16]. Given the toxicity of tin-based compounds, there has been significant interest in developing alternative halogen-atom-transfer reagents. Borane, alkylamine, and silane compounds have emerged as effective XAT reagents upon

• photocatalytic activation (Figure 1b) [17][18][19][20][21]. A photocatalytic HAT or SET generates the corresponding boryl, α-amino or silyl radical, which can abstract a halogen atom from alkyl halides to form the corresponding alkyl radical. However, the use of TTMS as a XAT reagent had already been established

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• inductive effect is attached to the carbon bearing the cyano group, the intensity of the absorption derived from the cyano group in the IR spectrum decreases significantly. This phenomenon has been reported, particularly in compounds where halogen or oxygen atoms are bonded to the carbon bearing the cyano

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• reductive elimination (path 1) [37][38][39]. This pathway initiates by formation of a halogen bond complex between 1a and the trifuoroethyl(mesityl)iodonium ion 2a’, where adduct XB-1 is presumably in equilibrium with isomeric XB-2. Reductive elimination of the iodoarene from XB-2 would furnish B, whose

• deprotonation would complete the pathway. The alternative mechanistic proposal is an SN2 reaction [40][41][42] between 1a and the iodonium ion 2a’, which directly furnishes B without invoking halogen bonded adducts. To assess which of these mechanistic possibilities was more probable, we turned to computational

• with them being viable electrophilic sites for halogen bond formation with 1a, supporting the mechanism in path 1. We also expressed the LUMO and LUMO+1 molecular orbitals of 2a’ (Figure 3, middle and right, respectively), which showed lobes centered on the I–C bonds to both the trifluoroethyl and

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• synthesis of various halogenated 1,3-oxazine 50 and 2-oxazoline derivatives 51 using boron trihalides as the halogen source [6][49]. They found that the choice of halogen source influences the reaction outcomes. With the use of BCl3 (Scheme 28), N-cinnamylbenzamides 52 were transformed to give the

• corresponding chlorinated dihydro-[1,3]-oxazines 50 in good to excellent isolated yields [49]. When various substituted N-(2-phenylallyl)benzamides (52) were tolerated, it led to the formation of chlorinated 2-oxazolines 51 in good to excellent yields. When BF3 was used as the halogen source in the author’s

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• substituent on the phenyl group, it is interesting to note that the most active compound of the whole series is the fluorinated derivative 18d, followed in order of inhibition by 18j, which has no substituents. The position of this halogen is also relevant since the activity decreases when it is in the 4

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• halogen-containing species (Scheme 33) [88][89]. Phenyltrimethylammonium tribromide (PTAB) was applied to the synthesis of peroxy-derivatives 93 of phenols and naphthols 92 in good yields. It was found that the I2/TBHP system allows selective functionalization of para-substituted phenols 94 with sulfonyl

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• strong C–N bond. The ring opening incorporated nitrogen, oxygen, sulfur, carbon, and halogen-containing nucleophiles and their derivatives. The substrate scope was examined with numerous aryl groups on iodonium salts 40 and the progress of aryl migration happens fruitfully by considering electronic

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• -donating (-Me, -OMe), electron-withdrawing (-NO2), and halogen (-Cl and -Br) substitutions on the aromatic ring were well tolerated under the reaction conditions. Pyrrole-fused triazolobenzodiazepines 6 were obtained in yields ranging from 72% to 91% (Scheme 4, 6a–h). Similar to the reaction of

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• organolithium reagents, thus limiting functional-group tolerance [11][12][13]. By contrast, heteroleptic (mixed) alkylzinc species (i.e., RZnX) are readily available and can typically be prepared from alkyl halides by direct insertion of metallic zinc into the carbon–halogen bond [14][15][16][17][18][19][20][21

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• porphyrins [34] and tetrabromoanthracenyl porphyrins [35]. In general, the halogen atom needed for the Suzuki coupling reaction resides on the porphyrin; however, Suzuki–Miyaura reactivity has also been shown to be reversed whereby the synthesis of borolanylporphyrins leads to a different approach to

• work has been done on the synthesis of ortho-substituted biaryls, by the groups of Buchwald [74], Snieckus [75], Ackermann [76], and Tang [77] among others. Many of these examples have steric hindrance ‘adjacent’ to that of the reactive halogen/boronic site as opposed to the ‘adjacent’ and ‘opposite

• ’ steric demand as seen with compound 11 with opposing bromines, coupled with the added complication of being a rotameric mixture, as well as adjacent hindrance of the nearby β-ethyl groups. Examples of palladium coupling on ‘opposing’ halogen atoms can be seen in the annulation of vic-bis(pinacolatoboryl

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• (R)-16 (Scheme 5). When the substituent R is an aromatic ring substituted by a halogen such as chlorine and bromine atoms, the amides (S)-23 were obtained in 22–27% yield and with very high optical purity ((S)-23b, (S)-23c), although as for (S)-23a, a satisfactory result (92% ee) could be obtained

• when the reaction was performed at 50 °C. The substrates with an aromatic ring substituted by not only an electron-withdrawing halogen atom but also an electron-donating group such as methoxy and methyl group also smoothly underwent the [1,3]-proton shift reaction, affording the desired products with

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

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

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• -chloro-1,1,1-trifluoroethane (halothane) in good yields (Scheme 1D) [42]. Compound 1 has a unique structure possessing three types of halogen atoms, namely bromine, chlorine, and fluorine, and it would be expected to afford multisubstituted fluoroalkenes by installing various substituents to bromine or

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• with halogen or triflate groups. Recently, transition-metal-catalyzed direct borylation of arenes via C–H bond activation has been reported, although the design of the substrate and ligands is somewhat complicated [16][17][18][19][20][21][22]. Since the complete removal of catalyst-derived metal