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

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

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• example, halogen-containing resorcin[n]arenes are highly sought after as they engage in divergent synthesis [8][63][64][65][66][67][68]. However, 2-haloresorcinol does not cyclize under standard protocols (Scheme 1a) pushing the need for an additional halogenation step (Scheme 1b). To overcome this

• synthon, which is used conveniently towards other applications, e.g., metal cluster synthesis, and halogen and hydrogen-bonded cavitands [77][78][79]. Our protocol works well with 2-methylresorcinol, as shown for products 1f and 1g, with significant yields around 80%. Electron-deficient and halogenated 2

• manner, and from the few reports using 2-bromoresorcinol, it has been described to yield inseparable mixtures of oligomers [9][59]. Electron-withdrawing groups like carboxylic acids are another useful functional group instead of the halogen that provide a divergent route to other functional materials

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• halo-divergent strategy from known 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-mannopyranose. In solution and in the solid-state, all analogues adopt standard 4C1-like conformations despite 1,3-diaxial repulsion between the F2 and the C4 halogen. Moreover, the solid-state conformational analysis of

• halogenated pyrans reveals deviation in the intra-annular torsion angles arising from repulsion between the axial fluorine at C2 and the axial halogen at C4, which increases with the size of the halogen at C4 (F < Cl < Br < I). Crystal packing arrangements of pyran inter-halides show hydrogen bond acceptor

• and nonbonding interactions for the halogen at C4. Finally, density functional theory (DFT) calculations corroborate the preference of talose analogues to adopt a 4C1-like conformation and a natural bonding orbital (NBO) analysis demonstrates the effects of hyperconjugation from C–F antibonding

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• 2 and 3 positions which clearly proved the epoxy ring opening taking place at the 2 position in an SN2 fashion (Figure 1). The introduction of an additional halogen atom was considered to be possible by treatment of 2b with an appropriate metal salt, and actually, similar results to the case of

• spectra for the compounds 11a and 11a-D. Expectation of the regio- as well as stereoselective reactions of 2. Attempts of the present epoxidation to other α,β-unsaturated esters, 1h–j. Introduction of additional halogen atoms at the 2-position of the compound 2b. Clarification of the stereochemistry of

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• Dominik L. Reinhard Anna Schmidt Marc Sons Julian Wolf Elric Engelage Stefan M. Huber Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Universitätsstraße 150, 44801 Bochum, Germany 10.3762/bjoc.20.204 Abstract Diaryliodonium(III) salts have been established as powerful halogen-bond

• . Finally, the potential as halogen-bonding activator was benchmarked in solution in the gold-catalyzed cyclization of a propargyl amide. Keywords: diaryliodonium; gold catalysis; halogen bonding; hypervalent iodine; non-covalent interactions; Introduction The compound class of diaryliodonium (DAI) salts

• in a Mannich reaction [4]. In 2018, our group showed in a proof-of-principle study [5] that the Lewis acid catalysis by DAI salts is based on halogen bonding (XB), an interaction between a Lewis base (XB acceptor) and an electrophilic halogen atom in the Lewis acid (XB donor) [6][7][8][9][10]. In

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• due to heat generation by electric resistance. With these results in hand, the substrate scope was investigated. First, the applicability of halogen-containing diphenylmethanol compounds 1b and 1c to the electrochemical carboxylation under the reaction conditions shown in Table 1, entry 8 was

• , 2H); 13C NMR (100 MHz, CDCl3, δ) 52.1, 125.5, 126.6, 126.7, 128.0, 128.3, 128.8, 137.6, 140.0, 177.8. Synthesis of diarylacetic acids 2 from diarylmethanol compounds 1 and carbon dioxide. Attempted electrochemical carboxylation of halogen-containing diphenylmethanol compounds 1b and 1c. Synthesis of

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• . The limitations in the scope of this methodology include a poor stereoselectivity achieved with 5-membered cyclic 2,3-disubstituted silanes in contrast to the 6-membered analogues (53). A lower efficiency was recorded with 2-substituted allylsilanes bearing either a halogen or an alkyl group with

• terminal halogen or acetate. The 2-ethynylallylsilane decomposed in the reaction conditions, while simple allyltrimethylsilane was unreactive. Among allylstannanes, the (3-phenylallyl)tri-n-butylstannane was also unreactive. Interestingly, both tetraallylsilane and tetraallylstannane gave racemic products

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

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• –13). In addition, 2-(pent-4-yn-1-yl)isoindoline-1,3-dione (1h) was utilized for the construction of the CF2 unit under the same conditions to give 2h (Table 2, entries 14 and 15). The substrate bearing a halogen, such as 10-iododec-1-yne (1i) in method A, produced the corresponding 2i in 60% isolated

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• products 2a–l. A variety of valuable functional groups on the benzene ring of 1b–j, such as methyl, methoxy, trifluoromethyl, and halogen atoms (F, Cl, Br, I), were well compatible with reaction conditions A. Most notably, unlike work by Li et al. [40], S-ethyl 3-oxo-3-(4-(trifluoromethyl)phenyl

• well as electron-withdrawing substituents on the two phenyl rings in compounds 1, such as methyl, methoxy, halogen atoms (F, Cl, Br, I), CF3 and SO2CH3, were well tolerated, and their electronic effects insignificantly impacted the formation of 3. Similarly, N-benzyl-3-oxo-3-phenylpropanamide (3w

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• from di-tert-butyldiazocarboxylate (23), aryl-substituted di-Boc-hydrazines 26 were prepared by the addition of aryllithium species generated in situ by lithium-halogen exchange of aryl halides [55]. Gerstenberger et al. used this entry for the one-pot synthesis of N-arylpyrazoles 25, as depicted in

• pyrazole 88 (Scheme 31) [114]. In addition to pyrazoles, functionalized pyrimidines can also be prepared in a one-pot process using this method. In 2001, Bouillon et al. reported a one-pot process for synthesizing fluorinated pyrazoles. Initially, a lithium–halogen exchange was carried out on fluorinated