Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• electron-withdrawing substituents. The reaction mechanism is based on the activation of the carbonyl group by molecular I2, through the formation of a halogen bond, which lowers the LUMO of the carbonyl moiety, increasing its electrophilicity, and thus allowing the addition of the indole group (Scheme 7

• reaction of aldehydes and ketones with indole [93][94]. Bidentate halogen-bond donors are efficient catalysts, since they can form two halogen bonds with each substrate, instead of just one. Thus, compounds 24, 25 and 26 were screened for their catalytic activity with 26 emerging as the optimum choice

• (Scheme 10). With catalyst 26 prepared, its use was then studied as a halogen-bond donor in the catalytic synthesis of 28 (Scheme 11) [93][94]. Having identified the optimum reaction conditions, the general applicability was studied by reacting various indoles with a range of aldehydes and ketones to

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• pattern shown in Figure 1, where R is the host atom or functional group to which the halogen is covalently bound, where X is the halogen atom possessing the σ-hole (halogen bond donor), and where Y is the Lewis base (halogen bond acceptor) [31]. σ-Holes arise from anisotropic covalent bonds between the

• influence σ-hole strength [32][48]. Should the halogen possess two covalent bonds, two σ-holes would result with the stronger situated opposite the more electron-attracting group [24]. σ-Holes are also highly directional, with near linear halogen bond-acceptor approach angles that typically fall between 160

• –180° [39][49][50], and with halogen bond lengths that are typically less than or equal to the sum of the atomic Van der Waals radii of the engaged atoms [33]. The strength of a subsequent halogen bond is influenced by the magnitudes of the positive electrostatic potential (VS,max) of the donor and the

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

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• aryl donors [11][12][13][14][15][16]. Their cyclic derivatives have a proven utility as precursors for the synthesis of hetero- and carbocycles [17][18][19][20][21], and their pronounced σ-holes [22] render them efficient halogen-bond donors (XB donors in XB catalysis) [23]. Despite their great

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -workers, with a strong focus on using rotaxanes with halogen-bond (XB) donors that act as binding sites for anionic guest molecules [23]. In 2017, Beer and co-workers reported the synthesis of the BINOL-containing chiral [2]rotaxanes 64 and their application for enantioselective anion recognition [63

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• and Scott showed [9] that in 50% acetone/50% water at 0.5 °C, a hydroxide ion was about 106 times more reactive than a water molecule towards benzenesulfonyl chloride. Also, for the same solvent, at 25.0 °C, they found [10] that the fluoride, with a considerably stronger carbon–halogen bond, reacted

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• -trifluorophenyl-type catalysts [45]. Additionally, the first asymmetric systems involving purely halogen bond donor catalysis have recently been developed by the groups of Huber [46] and García Mancheño [47]. Moreover, though chloride as halide counter-anion still being particularly prominent, the application of

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• hydroalkylation product 92e’, indicating a possible double bond isomerization under these reaction conditions. The postulated mechanism starts with the generation of an ethyl radical from BEt3. This radical then acts as a radical initiator to promote the homolytic cleavage of the carbon–halogen bond of the α-EWG

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• spectroscopy shows that phosphono radicals could proceed throughout the reaction. A halogen bond (XB) is a noncovalent interaction formed between a halogen atom and a neutral or negatively charged Lewis base. It is a kind of weak intermolecular interaction analogous to a hydrogen bond and basically can be

• considered as a specific EDA complex [62]. In 2016, Yu and colleagues [33] employed perfluoroalkyl iodide 6 as halogen-bond donor (electron acceptor) and the organic base dibenzylamine as the halogen-bond acceptor (electron donor) to form the XB complex 8, and then a fluoroalkyl radical was given via visible

• -bond adduct. The first light-promoted three-component reaction has been realized by a halogen-bond adduct, forming perfluoroalkylated pyrimidines 26 (Scheme 8). A variety of perfluorinated chains were assembled with methylene compounds and guanidines or amidines, giving the corresponding

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• of iodofluorobenzene derivatives with nitro-cyanostilbenes is reported. The systematic variation of the fluorination degree and pattern indicates the relevance of the halogen bond strength for the induction of liquid crystalline properties. The modular self-assembly approach enables the efficient

• groups employed halogen bonding for the formation of liquid crystalline materials [8][9]. For instance, Palacio et al. used (E)-1-(4-(octyloxy)phenyl)-2-(2,3,5,6-tetrafluoro-4-iodophenyl)diazene as a photo-switchable halogen bond donor and investigated the light-induced phase transition of the complexes

• fluorine substitution of the aromatic halogen bond donor on the liquid crystallinity and the photo-response of halogen-bonded liquid crystals [12]. However, all reported halogen-bonded liquid crystals rely on the halogen-bond-acceptor capability of pyridyl units and so far, no study on the fluorescence

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• reactivity [25]. The triplet state energy of carbonyl compounds can also be transferred to halogen-containing compounds, leading to the homolytic dissociation of the carbon–halogen bond. This interaction has been studied for tert-butyl chloride, where the descendant radical is quite stabilized [26]. The

Halogen-bonding-induced diverse aggregation of 4,5-diiodo-1,2,3-triazolium salts with different anions

• Xingyu Xu,
• Shiqing Huang,
• Zengyu Zhang,
• Lei Cao and
• Xiaoyu Yan

Beilstein J. Org. Chem. 2020, 16, 78–87, doi:10.3762/bjoc.16.10

• dimers, respectively, while the former shows boat conformation and the latter forms rectangle conformation. Triazolium salts form a linear polymer with polyiodide. Keywords: aggregation; 4,5-diiodo-1,2,3-triazolium salts; halogen bond; non-covalent interaction; Introduction The halogen bond (XB) is a

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• , exemplified by partial agonist 1c and equal full agonists 1d and 1e (VUF11418, Figure 2A). A tentative explanation for this efficacy switch includes a variation of the dihedral angle of the biaryl moiety, an increase of the electron density in the biaryl unit and/or a postulated halogen bond of the halogen

• azobenzene analogue 2a, we explored the substitution pattern of the outer aromatic ring with chlorine atoms in the ortho, meta and para-position (compounds 2b–d, respectively) to also assess the possibility of agonism provided by a halogen bond. Compound 2e, which contains a bromine atom in the ortho

• –f with E values between 30–50% at 10 µM. Interestingly, one of these compounds (4f) includes a methyl group as ortho-substituent on the outer ring and its agonist effect at PSS amounts to 32%, possibly questioning one of our hypotheses that a halogen bond is involved in inducing CXCR3 agonism

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• -triazole units to more electrophilic 1,2,3-triazolium units by influencing both hydrogen bonding-like and anion–π interactions. Moreover, halogen bond (XB) and chalcogen bond (ChB) interactions (see Figure 1) also been applied for the selective detection of anions by exchanging C5–H protons with halogens

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• azobenzenes with different halogen bonding donor properties are discussed in relation to their changing photophysical properties, rationalized by DFT calculations. Keywords: azobenzene; DFT calculations; fluorine chemistry; halogen bonding; photochemistry; Introduction The halogen bond is an attractive

• noncovalent interaction between a polarized halogen atom (the halogen bond donor) and a Lewis base (the halogen bond acceptor) [1][2]. A prominent example regarding the origin of halogen bonding can be found in inorganic solid-state chemistry. The structurally diverse group of polyiodides, with its rich

• structural chemistry is governed by halogen bonding, where I− and I3− are considered the nucleophilic (halogen bond acceptor) and I2 the electrophilic (halogen bond donor) subcomponent [3][4][5][6][7]. Neutral halogen bonds on the other hand can be generally described by R–X···Y, where R–X is the halogen

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• chloride (2), and 1,4-diiodooctafluorobutane and accompanying small solvent guests (methanol, acetonitrile and water) are presented. The guests’ inclusion affects the geometry of the cavity of the receptors 1 and 2, while the divalent halogen bond donor 1,4-diiodooctafluorobutane determines the overall

• nature of the halogen bond assembly. The crystal lattice of 1 contains two structurally different dimeric assemblies A and B, formally resulting in the mixture of a capsular dimer and a dimeric pseudo-capsule. 1H and 19F NMR analyses supports the existence of these halogen-bonded complexes and enhanced

• halogen bond acceptors [29][30][31][32][33][34]. We have previously shown that N-alkylammonium resorcinarene bromides (NARBrs) can form various halogen-bonded assemblies with the classical organic halogen bond donor 1,4-diiodooctafluorobutane (DIOFB) depending on the solvent, the presence of potential

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• reagents and frequently these reactions are carried out at room temperature and at atmospheric pressure, etc. [16][17][18][19]. The electrochemical behavior of halogenated compounds has been extensively investigated [20][21][22]. The cleavage of the C–halogen bond, yielding (via a radical intermediate) the

• corresponding carbanion and halogen anion, can be achieved by a bielectronic cathodic process (Scheme 2). The electrolysis is carried out at a suitable controlled potential, i.e., at a potential that is negative enough to achieve the selective fission of the envisaged C–halogen bond [23]. Therefore, the

• = 25 °C; solvent left: DMF/Et4NBF4 0.1 mol dm−3; right: ACN/Et4NBF4 0.1 mol dm−3. Variation of the amounts of 1a, 2a, and 3a with the number of Faradays of 1a. The Corey–Fuchs reaction. Electrochemical reduction of a carbon–halogen bond. Electrochemical synthesis of vinyl bromides [25]. Scope of this

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• allylic halides were also subjected to these conditions. It is notable that the trifluoromethyl group was introduced at the α position of the carbon–halogen bond with complete regioselectivity. Later, they extended these conditions to propargylic halides [27] and succeeded in synthesizing the

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• carbon–halogen bond known [1]. Its low reactivity, in comparison to other C–X bonds, means that it is inert to all but the most harsh reaction conditions, and fluorine can generally be carried through multistep syntheses without concern over side reactions (the exception being SNAr reactions). In recent

Conformational preferences of α-fluoroketones may influence their reactivity

• Graham Pattison

Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284

• -haloacetophenone, calculating the energy of each compound as the carbon–halogen bond is rotated through 10° increments in both the gas phase and in ethanol as reaction solvent (Figure 1) [10]. The fluorinated acetophenone showed significant differences in conformational energy to the chlorinated and brominated

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• of an halogen bond between the positive electrostatic potential on the outer side of the chlorine atom and the lone pair of the phosphorus atom of the phosphine. This phenomenon indeed triggered the cleavage of the S–Cl bond, producing chlorophosphonium sulfinate 40, which was then readily converted

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• observed in the molecular structures of the metallocene–nucleobase derivatives [24][29]. In addition, each molecule of 2 in the dimer is further involved in a Cl···O halogen bond with an adjacent molecule of chloroform (Figure 3). Further details of intermolecular interactions present in the crystal

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• bands at 1099 (Cl), 1077 (Br) and 1064 (I) cm−1 which are assigned to vibration of the phenyl ring that contains the carbon–halogen bond. Characteristic C≡C alkyne band at 2133 cm−1 along with the band at 1258 cm−1 of the triazole products are appropriate for monitoring of the reaction progress. In situ

Detection of therapeutic radiation in three-dimensions

• John A. Adamovics

Beilstein J. Org. Chem. 2017, 13, 1325–1331, doi:10.3762/bjoc.13.129

• consistent with the bond energy of the carbon–halogen bond. The observed sensitivity was in the order R3C–I > R3C–Br > R3C–Cl [42][43][44]. Due to the high electron density of radical initiators containing iodine even at relatively low concentrations (100 mM) result in dosimeters that are not tissue