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

• functional groups and avoids the use of highly toxic and corrosive bromine. Approaches using this approach are outlined below. Nitrogen nucleophiles In 2007, aminobromocyclisation of homoallylic sulfonamides 53 was reported by Fan, Wang and co-workers (Scheme 29) [50]. Using PhI(OAc)2 as an oxidant with KBr

• as the bromine source and Bu4NBr as a reaction promoter, racemic brominated pyrrolidines 54 were synthesised from a range of homoallylic sulfonamides 53 in excellent yields under mild conditions at room temperature. A mechanism was suggested by the authors (Scheme 29), whereby ligand exchange on PhI

• (OAc)2 with a bromide ion forms unstable PhIOAcBr. Elimination of bromoacetate then gives a reactive electrophilic bromine source, which forms a bromonium intermediate A after reaction with the alkene. Intramolecular nucleophilic attack from nitrogen forms the product 54. Chiba and co-worker reported

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

• -Butoxy and tert-butylperoxy radicals are generated through the redox reaction of bromine. Vanadium(IV) oxychloride (VOCl2) was found to be an efficient catalyst to achieve peroxidation–carbonylation of styrenes 152 with TBHP and aldehydes 153 to give β-peroxy ketones 154 (Scheme 48) [112]. V(IV)OCl2 is

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

• illustrates that coupling phenyl, thiophene or other aryl moieties at this position would be extremely difficult. Furthermore, the distance between the o-bromine atoms and the nearest carbon neighbor of the β-ethyl groups is 3.7 Å, further complicates the success of coupling at this position. As discussed

• previously, enrichment to the αβαβ, isomer may be necessary to remove the impact of opposing bromine atoms on the coupling reaction. Separation of the four individual atropisomers (αβαβ, α2β2, α3β, α4) has been accomplished before in dodecasubstituted porphyrins through Ni(II) metalation [15]. The core

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

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

• fluorovinyl ethers, which contains a reactive bromine atom, to afford a series of fluoroalkenes and fluoroenynes in moderate to high yields. Keywords: fluoroalkenes; fluoroenynes; multihalogenated vinyl ethers; Suzuki–Miyaura cross-coupling reactions; Sonogashira cross-coupling reactions; Introduction

• -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

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

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

• depending on the incorporated halogen on the pyran core at C4: −208.33 ppm for 12 (fluorine), −197.95 ppm for 13 (chlorine), −192.80 ppm for 14 (bromine), and −184.56 ppm for 15 (iodine). Similarly, the increase in chemical shift of F2 is smaller as exemplified with an upfield shift of −205.46 ppm for 12 to

• exception being bromine). Dipole moments for the 4C1 structures are 2 Debye larger than for 1C4 structures, making them substantially more stable in chloroform. Both chair structures have multiple C–F bonds in gauche arrangements which are stable due to hyperconjugation: there is donation from C–H bonding

• , 17, and α-ᴅ-talose 18. ORTEP diagram showing 50% thermal ellipsoid probability (except for 18): carbon (gray), oxygen (red), fluorine (green), chlorine (orange), bromine (dark red), iodine (purple), and hydrogen (white). Packing arrangement of compound compound 15; a) View down the b axis; b

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

• ). Halogen bonding dimer found in the crystal structure of 7Br. Ellipsoids are shown at 50% probability (carbon: grey, nitrogen: blue, oxygen: red, bromine: orange, iodine: purple) and hydrogen atoms are shown in standard ball-and-stick model (white). Halogen and hydrogen bonding is indicated dashed. 1H NMR

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• -Addition of molecular bromine to phenyl isocyanide was reported by E. Kühle et al. to afford the corresponding 1,1-adduct (PhN=CBr2) [23]. Since dichloro compounds (RN=CCl2) [24] are the imino derivatives of highly toxic phosgene (O=CCl2), reactions using them as key intermediates are not safe synthetic

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

• generated hydrazones were cyclized with simple ketones to pyrazolines. The oxidation to the corresponding 4-halo-substituted pyrazoles 69 can be achieved in a one-pot fashion by halogenation with iodine chloride or elemental bromine (Scheme 24) [102]. When cyclic ketones are used, fused products 70 are

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• -difluoroethylene and the disappearance of vinyl protons resonances in the 1H NMR spectra [78]. Addition to the C=C bond Halogen addition: 1,2-Difluoroethylene was reported to react with chlorine [46][79] and bromine [51] under irradiation, yielding 1,2-difluoro-1,2-dihaloethanes in moderate to high yield (Scheme 9

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• spectra were acquired on Bruker 300 MHz spectrometers equipped with 5 mm BBFO probes. HRMS data were acquired using an Agilent 6530 LC/Q-TOF using a Dual AJS/ESI ion source, and the isotope 79 was used for HRMS analysis for any bromine-containing compounds. Synthesis All procedures and spectra can be

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• the described conditions. The halogen groups on the anilines slightly decreased their reactivity, leading to the formation of products 2q–w with lower yields. However, the 8-chlorine derivative 2u with a o-tolyl aldehyde moiety was prepared with a yield of 37%. Aromatic aldehydes bearing bromine and

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• bromolactonization product 3a. It should be noted that the asymmetric reaction using bromine (Br2) as a brominating reagent gave product 3a in a racemic form. Additionally, iodolactonization of 2a using N-iodosuccinimide in the presence of catalyst (S)-1g was performed. The reaction in dichloromethane, however

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V

• bromine trifluoride (Scheme 2B) [21][22]. They also showed that hypervalent iodine(V) fluoride 3 fluorinated phenylmagnesium bromide in Freon-113 to form fluorobenzene in 90% yield (Scheme 2A) and so, it is very surprising that this reagent has not been investigated further. Since then, Gruber [23

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

• . In contrast to the suggested traceroute where the chlorine or bromine atom is attached to the hypervalent iodine center of the plausible reagent PhIX2 (X = Cl, Br), our new protocol opens up a broad path for the reaction through different halogenating species. For a deeper understanding of these

• reference. At this stage, the PIDA–AlBr3 adduct undergoes ionization, giving rise to the corresponding ion pair I-1–Br (ΔG = −31.3 kcal/mol) in a highly exergonic and energetically favorable process. Next, an intramolecular SN2 reaction of the formed aluminum anion transfers a bromine atom to the

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• become staples in organic chemistry, the exploration of their isoelectronic counterparts, namely hypervalent bromine(III) and chlorine(III) reagents, has been relatively limited, partly due to challenges in synthesizing and stabilizing these compounds. In this study, we conduct a thorough examination of

• results of this study could aid in estimating the chemical stability and functional group transfer capabilities of hypervalent bromine(III) and chlorine(III) reagents, thereby facilitating their development. Keywords: BDE; cyclic hypervalent halogen reagents; DFT calculation; graph attention network

• ][22], unsaturated alkane addition [23][24], and cyclization [25][26]. Despite the rapid development of hypervalent iodine(III) reagents, the exploration of isoelectronic hypervalent bromine(III) and chlorine(III) reagents has been comparatively limited despite their demonstrated potential for unique

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• (THF) incorporating Huber, Truhlar, and Cramer’s correction for bromine and iodine [32] using Gaussian 09 [33]. Our prior work on the orbital analysis of diarylhalonium salts [21], showed good agreement between crystal structure data and energy-minimized structures at the B3LYP/cc-pvtz level with def2

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• enabling the activation of small yet highly relevant organic substrates. For example, Huber and co-authors recently designed a Te-based catalyst in an indole Michael addition reaction [1][2][3][4][5]. Pale and Mamane utilized another Te-based catalyst in an electrophilic bromine-mediated cyclization

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

• corresponding α-bromoketones (2a,b) in 49–54% isolated yields by oxidative transposition of the bromine atom in the reaction process. We then extended this scope by synthesizing unsymmetrical dialkyl bromoalkenes (1c–g) bearing side chains of varied length and steric character. The incorporation of n-pentyl or

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

• significant importance as reactive building blocks in polymer and materials chemistry. Their preparation primarily relies on established synthetic methods using molecular bromine or N-bromosuccinimide, known for their reliability and effectiveness. However, from a sustainability perspective, these methods

• considering the most atom-economical options, namely chlorine and bromine, the latter typically exhibits some advantages over the former. These include: (i) better regioselectivity in radical processes, attributed to the lower bond enthalpy of H–Br (88 kcal/mol) compared to H–Cl (103 kcal/mol) [17], (ii

• 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

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• supernatant. There are two main types of molecular probes based on their detection methods: imaging and UV–vis (Figure 2A). An imaging probe contains a mass spectrometry (MS) tag, oftentimes a halogen with a distinct isotopic ratio such as chlorine or bromine. A UV–vis probe contains a UV-tag, such as an

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

• , only the double-substituted product could be found. No reaction was observed when the reaction temperature was lowered to 0 °C. This could be due to the double activation of the 5-position, despite the fact that bromine is a better leaving group than chlorine. Both positions might be influenced by the

• functional groups adjacent to them, due to withdrawing effects. Chlorine has a stronger electron-withdrawing effect than bromine, so the electrophilic character of the 6-position should be higher than that of the 5-position. However, it is unlikely to be the only reason for the formation of just one

• carried out by application of the Suzuki–Miyaura cross-coupling. The optimization was carried out with 3a as the model compound (Table 1). The starting material 3a is a sterically hindered system in which the bromine is only partially accessible, due to the large residue. This could be the reason for the

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• generally moderate to good yields of 22–83% (Table 2, entries 1–17). These substituents included halogen (Br), methyl, phenyl, aldehyde, ester, and methoxy groups, all of which were compatible with the reaction conditions. Notably, compounds 3ab, 3ah, 3aj, 3am and 3ap bearing bromine are very useful modules