Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• ; heterocycles; photocyclization; photosensitizer; styrylpyridines; Introduction DNA intercalators – most often represented by small planar heteroaromatic compounds – play an important role as chemotherapeutic agents [1][2][3][4]. Specifically, upon intercalation into the DNA double helix such ligands can cause

• delivered without effect to the binding site, where the DNA-binding benzoquinolizinium ligand can then be generated as needed upon irradiation. Notably, the use of light for the activation of photo-controllable DNA ligands offers several advantages because it is easy to apply, traceless, and non-invasive

• -based nanoparticles [58][59]. But although these classes of compounds have been intensively studied and already contributed significantly to the field of PDT, there is still a demand for novel DNA-photodamaging ligands that could be applied for specific purposes, e.g., to improve efficacy or to limit

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• candidates as well. Ortho-hydroxy-substituted phosphines have been mainly used as chelating ligands for metal complexes until recently [16][17][18]. Further, ortho-hydroxy phosphines have been used for the synthesis of probes in metabolic labeling [19], as a photocatalyst in the defluoroalkylation of

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• -heterocyclic carbenes (NHCs), extensively studied as organocatalysts as well as ligands for transition-metal-promoted synthetic methodologies [97][98][99]. Under anodic oxidation, the electrogeneration of boron trifluoride (BF3) from tetrafluoroborate ILs occurs [100][101]. Moreover, we have recently

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• heterocycles; zwitterions; Introduction Following the seminal discovery from the group of Arduengo, who isolated and fully characterized 1,3-di(1-adamantyl)imidazol-2-ylidene in 1991 [1], stable divalent carbon species have evolved from fleeting intermediates to ubiquitous catalysts, ligands, and reagents in

• of charges (Figure 1) [13][14][15][16]. Crabtree and co-workers first reported the abnormal binding of an imidazolium salt to an iridium hydride at the C4 carbon atom instead of C2 in 2001 [17][18]. Since then, many other metal complexes bearing imidazol-4-ylidene ligands (F) have been reported [7

• ][19]. These mesoionic carbenes (MICs), together with their pyrazolin-4-ylidene [20] and 1,2-isoxazol-4-ylidene cousins [21], are the strongest donors among the various types of carbene ligands known thus far [22]. A distinct class of mesoionic or abnormal carbenes based on the 1,2,3-triazole ring

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• in the 1BFC [12] and 2AXM [13] complexes and chondroitin sulfate-4 in the case of 3C9E [36]/4N8W [37]), where the length is dp6 (dp stands for degree of polymerization) and 2. an additional part with different degree of sulfation or sulfation pattern (in case of ligands 1 and 2 for 1BFC and 2AXM dp6

• 1C4 conformation for the IdoA2S ring was chosen as it was shown to be the essentially dominant conformation in the microsecond scale simulations performed by Sattelle et al. as it is energetically more favorable than the 2SO conformation [40]. Complex preparation The obtained ligands were docked using

• RS-REMD (replica exchange with repulsive scaling), an MD-based docking method [41], to assure proper binding poses of the whole ligand and ring puckering and to be consistent with further simulations. The docked ligands cover the binding site the same way as ligands in the experimental structures

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• , including both aromatic and saturated NH-substrates. This yields structures that are appealing for generating cereblon ubiquitin-ligase ligands and for potential use in crafting PROTAC molecules. Keywords: CRBN ligands; diazocarbonyl compounds; N–H insertion reaction; N-heterocycles; Rh(II)-catalysis

• strategies is cereblon (CRBN), the target focus of a collection of immunomodulatory drugs containing the glutarimide moiety such as thalidomide, pomalidomide, lenalidomide [12][13], and avadomide [14] (Figure 1). These ligands, although prevalent recruiters in PROTAC design, present several drawbacks

• space of cereblon ligands. Research teams and pharmaceutical companies worldwide are actively conducting studies to discover new CRBN ligands based on α-hetaryl-substituted glutarimides of general formula 1 (Scheme 1). Consequently, a significant number of patents describing the synthesis of new PROTAC

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• (26.6 ppm) in the Earth crust [26]. Although it should not be considered a cost-effective option at present, as several social and environmental concerns are associated with its extraction, the high stability of the Co(II) ion and the versatility of the ligands used for coordination offer some

• advantages for tailoring new catalysts to specific reactions and optimize selectivity [22][27]. Cobalt catalysts successfully employed in CO2 reduction are mainly based on macrocyclic ligands, such as tetraazacyclodecene and its derivatives [3][28][29], porphyrins [30][31][32][33][34], or phthalocyanines [35

• ) [39][40], and two thiocyanate ligands. As observed for other cobalt complexes [21], the photoinduced CO2 reduction gave preferentially molecular hydrogen, when performed in acetonitrile. Moreover, we targeted a photocatalytic system that is fully earth-abundant. For this reason, we selected the known

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• thus less side-effects in therapy [23]. In this sense, we have reported dicopper(II) complexes from different N-acylhydrazonic binucleating ligands with potent antiproliferative activity against a panel of cancer cell lines [24][25][26]. On the field of neurodegeneration, our research group was the

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• oligo(ethylene glycol) segment. These hybrid systems constitute a broad group of compounds, including crowned porphyrins, crownphyrins, and calixpyrrole-crown ether systems forming Pacman complexes with transition metals. Their unique nature accustoms them as excellent ligands and hosts capable of

• /electrostatic interactions [18][19][20]. Replacing oxygen atoms with other elements, such as nitrogen, sulfur, etc., alters the crown ethers' affinity toward cations, extending their role as macrocyclic ligands to transition metals [21]. One can say that in many aspects, porphyrins and crown ethers are

• laid the ground for a whole new research area of hybrid imine-porphyrinoids [52][53][54]. Bowman-James' work provided an exciting insight into accordion porphyrins' coordination chemistry, demonstrating the tremendous potential of iminoporphyrinoids as macrocyclic ligands. Independently the Sessler

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• caused by its structural features. NHCs constitute a well-established class of new ligands in organometallic chemistry. Although initially NHCs were regarded as pure σ-donor ligands, later experimental and theoretical studies established the presence of a significant back donation from the d-orbital of

• . A number of excellent reviews on different aspects of NHC chemistry has been published during this period [12][13][14]. NHCs have been widely employed in homogeneous catalysis [12] and as ligands for the preparation of coordination compounds of different metals [13]. The M–NHC bond is relatively

• ligands in organometallic chemistry. After the first synthesis of stable monomeric NHCs, spectroscopic studies promptly revealed their similarity with phosphines. Indeed, both these classes of ligands are σ-donor ligands with low π-backdonating character [16][17]. In the beginning, the NHCs were perceived

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• abstained from the conversion of compounds 24, 25 or 26 into their sulfated form due to the presence of the impurities in these samples. However, only the sulfated forms of this type of multivalent carbohydrate mimetics had earlier shown respectable biological activity as ligands of P- and L-selectins [44

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

• performance in OLED devices [1]. 4CzIPN is a donor–acceptor-type system where carbazole donor ligands are bound to the benzonitrile acceptor core moiety. In this work we have substituted the carbazole donors with 5H-benzo[d]benzo[4,5]imidazo[1,2-a]imidazole (benzoguanidine) ligands to give 4BGIPN, see Figure

• donor ligands above or below the central 4,6-dicyanobenzene ring. In the monoclinic form the two independent molecules of 4BGIPN are related by a pseudo glide plane that do not completely align when superimposed through a glide operation. There is no evidence for systematic absences relating to the

• experiment from 1.402(5) to 1.420(5), giving an average of 1.407(13) Å for 4BGIPN, which is closely similar to 1.405(8) Å reported for the benchmark 4CZIPN compound. Unlike carbazole, the benzoguanidine ligand lacks C2 rotational symmetry, thus enabling the benzoguanidine ligands to project above and below

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• demonstrated to be particularly privileged in delivery of various ligands to alkyl radicals (Scheme 2). These developments have been supported by discovery of the compatibility of RLT with many different reaction paradigms leading to alkyl radical intermediates under catalytic conditions, including radical

• functionalization via the canonical organometallic steps of oxidative addition/reductive elimination was ruled out via catalytic reaction of the macrocyclic Groves-type porphyrin catalyst V, a species that is unable to accommodate the mutual cis-orientation of ligands for metal-centered reductive elimination. The

• the dual catalytic ATRA-RLT cycle. III: Our lab and Xu reported photochemical diazidation of alkenes carried out using iron and trimethylsilyl azide. IV: The proposed mechanism for photoinduced LMCT between iron and azide ligands as well as RLT on azidoalkyl radical intermediates. Pioneering and

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

• generate intermediates 2 or 3, where the cis-oriented ligands may reductively eliminate to generate either a functionalized β-dicarbonyl (4, most common) or a substituted arene (5, rare). Interestingly, when the first iodonium ylide was synthesized by Neiland and co-workers in 1957, they also evaluated its

• analogous free-carbene mediated reactions, and they instead proposed iodine to have engaged with Lewis basic ligands and coordinated their coupling within its ligand sphere. An ylide’s positively charged iodine was consistently proposed to accept ligands, via either concerted or ionic steps, ultimately

• - and hydrogen intermolecular bonds. This adduct decomposed by reductive elimination of the iodoarene via a three-membered transition state (TS), coupling the syn thioamide and β-dicarbonyl ligands to give thiocarbenium ion 74. The authors determined similar activation energies (≈20 kcal/mol) when

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• phosphine oxide, and selenides to selenoxides. Sulfoxide, phosphine oxide, and selenoxide-containing molecules have diverse applications in the pharmaceutical industry [10], as chiral auxiliaries or as ligands for asymmetric metal catalysis [11], and in materials such as polymers [12][13] and flame

• retardants [14]. Sulfoxides are prominent pharmaceutical ingredients, while phosphine oxides improve solubility of corresponding compounds [15] and have applications in catalysis and materials science [16]. Selenoxides find use as oxygen transfer agents and donor ligands in metal catalysis and organic

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

• excited state lifetimes [95][96], most reactions employing such photocatalysts require special reaction design (e.g., coordination of substrates as ligands to enable intramolecular metal to ligand charge transfer (MLCT)). Only recently have a few examples been reported that observed bimolecular quenching

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• strategies for C–N bond formation have been extensively explored by various research groups for the N-arylation of amines. Specifically, seminal contributions by Buchwald [15] and Hartwig [16] involving the use of palladium complexes as catalysts in the presence of either phosphine or diamine ligands for C–N

• bond formation. However, these methods suffer from limitations such as moisture sensitivity, the requirement of specific ligands, and the use of expensive palladium catalysts [17]. Also, Chan Lam, Evans, and other research groups have developed copper-catalyzed C–N bond formation reactions by careful

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• reactions include mild reaction conditions and the use of a sole catalyst without the need of other chiral ligands [4][5]. In these reactions, stereoinduction in the products is achieved by the chiral environment present in the catalyst itself. Depending upon the reactivities, organocatalysts can be

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• method using a zinc catalyst. The synthesis of pyrrole derivatives 47 were achieved in moderate to excellent yields without using any co-catalyst, ligands or bases by stirring various aniline derivatives 46 with 2,5-dimethoxytetrahydrofuran (2) in the presence of 5 mol % of Zn(OTf)2 for 8 hours at 70 °C

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• reactivity of their alcohol functions. This allows regioselective chemical modification at either the primary or secondary rim [13]. As a result, these molecular hosts can be specifically linked either covalently or noncovalently to a wide variety of ligands. CDs are a significant part of almost all areas of

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• demonstrated that the reaction in the presence of cationic zirconium complexes derived from zirconium dibenzyl complexes bearing tridentate [ONO]-type amine-bridged bis(phenolato) ligands and [Ph3C][B(C6F5)4] (Scheme 5), gave rise to ortho-selective C–H alkylated pyridines 19 and 21. It was observed that the

• dialkylpyridines with alkenes. It is to be noted that the ligands’ backbones were found to be crucial for the regioselectivity of the addition to benzylic C(sp3)–H bonds, as N-arylamine-bridged bis(phenolato) Zr complexes provided branched products whereas N-alkylamine-bridged bis(phenolato) Zr complexes provided

• imines 25 (Scheme 6). The authors also demonstrated the enantioselective aminoalkylation, using chiral diamines as ligands. The introduction of chiral diamines in the metal complex produced the aminoalkylated products enantioselectivity with good ratio of enantiomeric excess. The plausible mechanism

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

• frameworks with dibenzo[b,f]azepine derived ligands have also been reported. This review provides a brief overview of the different synthetic strategies to dibenzo[b,f]azepines and other dibenzo[b,f]heteropines. Keywords: dibenzo[b,f]azepine; dibenzo[b,f]heteropine; dibenzo[b,f]oxepine; iminostilbene

• ; synthesis; Introduction The dibenzo[b,f]azepine (1a) scaffold (Figure 1) is featured in commercial pharmaceuticals [1] and other lead compounds [2][3][4], ligands [5][6] and in materials science with possible applications in organic light emitting diodes (OLEDs) [7] and dye-sensitized solar cells (DSSCs

•  31). The reaction conditions were screened with several biarylphosphine ligands and Pd sources. Excellent yields were achieved with a low catalyst loading of RuPhos (L6) fourth generation palladacycle precatalyst L6 Pd G4 (Scheme 31). The authors evaluated an extensive series of aryl halides. The

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• the catalytic antibody [24]. They are also potential chiral ligands in asymmetric catalysis [25] (Figure 1). Cyclizations and annulations are two major strategies for the synthesis of medium and large phostam, phostone, and phostine derivatives. The cyclizations have been applied in the construction

• –elimination. Both they are potential chiral phosphorus ligands (Scheme 20) [25]. When Fuchs and co-workers investigated the conversion of cyclic vinyl sulfones to vinylphosphonates, they found that the reaction of (1S,2R)-2-methyl-3-(phenylsulfonyl)cyclohept-3-en-1-ol (100) and diethyl phosphonate generated

• because the P–O bond is more stable than the corresponding P–N bond. Much attention should be paid to the synthesis of different ring size phostams in the future. Biologically active agents and chiral ligands containing medium and large phostams, phostones, and phostines. Synthetic strategies for the

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• (Scheme 16). Within the framework of these domino reactions, we have mainly employed ferrocenyl phosphane ligands such as Taniaphos or Josiphos. In collaboration with Prof. Schmalz from Cologne University, we have also tested phosphite-phosphine ligands (e.g., L15) from their lab. The advantage of these

• ligands is that they can also promote the conjugate additions of aryl-based or branched Grignard reagents (Scheme 17) [49]. Further extending this methodology, we have investigated formaldehyde imine equivalents. These kinds of imines are not readily available, but they are highly important synthetic

• ring, while flavylium triflate and 2,4,6-triphenylpyrylium tetrafluoroborate were not compatible with our reaction conditions. Heterodonor ferrocenyl phosphane–carbene ligands efficiently promote the conjugate addition of Grignard reagents to α,β-unsaturated lactones [58]. Building on this knowledge

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• (L1)3] (comp3) catalysts allowed to show, on the one hand, the absence of solubility problems, and to discover, on the other hand, that the presence of three L1 ligands (comp3) leads to a reaction rate clearly lower than that of a catalyst carrying one or two ligands (see p. S7 of Supporting

• Information File 1 for the reaction kinetic curves of catalysts). In addition, the catalyst with a single L1 ligand (comp1) was found to be more reactive than the one with two ligands (comp2), and was therefore selected for further optimization. In contrast, comparison of its reaction kinetic curve with that