Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• . This method allows for the hybridization of complex bioactive and fluorescent-labeled carboxylic acids with diaryliodonium(III) salts. Keywords: auxiliary ligand; diaryliodonium(III) salts; hybridization; hypervalent iodine; organocarboxylates; Introduction Hypervalent iodine compounds are an

• -arylation using aryl(2,4,6-trimethoxyphenyl)iodonium(III) acetates [13]. In this process, the acetate ligand acted as a base to activate the phenol group and positioned it in proximity to accomplish the smooth SNAr reaction. The synthesis of diaryliodonium(III) salts with various counterions, such as

• reported [18][19] (Scheme 1). The importance of the trimethoxyphenyl (TMP) group as an auxiliary (dummy) ligand on the iodonium salt has prompted researchers to synthesize aryl(TMP)iodonium(III) trifluoroacetates via oxidation of iodoarene with m-chloroperbenzoic acid (mCPBA) in the presence of

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• protocol the use of a Lewis base such as SnCl2 was not required and the reaction took place under milder conditions using Pd(OAc)2 as catalyst and PPh3 as ligand. The reaction was performed at 70 °C for 15–48 hours, under 4 bar of CO in a DMF/MeOH 2:1 mixture giving the indole derivatives without obvious

• second case the reactions were catalyzed by 6 mol % of Pd(OAc)2 and carried out under 4 bar of CO. The fused indoles were obtained when adding 24 mol % of dppp (1,3-bis(diphenylphosphino)propane) at 120 °C for 70 hours in DMF. Instead, in the other case, PPh3 was used as ligand at 70 °C for 17–46 hours

• as ligand, because it was already known that catalysts derived from palladium(II) salts and bidentate nitrogen ligands were highly reactive systems for the reduction of o-nitrostyrenes [28][29][30]. The catalytic system Pd(OAc)2/1,10-phen worked better than Söderberg´s one (Pd(OAc)2/PPh3) under mild

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation

• -lactam ring is a privileged scaffold widely present in drugs and natural products [12][13][14], as shown in Scheme 1. Herein, we report the effective desymmetrization strategy of N-protected 2,5-dihydro-1H-pyrroles using aryldiazonium salts and the chiral N,N-ligand (S)-PyraBox (Scheme 2). The obtained

• the palladium source in combination with the pyrazinebisoxazoline ligand, (S)-PyraBox (L1), zinc carbonate as base, and methanol as solvent at 40 °C. These initial conditions furnished 2-methoxypyrrolidines arylated at the 4-position, compound 3, as Heck products as illustrated in Scheme 3. The

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• validation report is the beginning of the carbohydrate information, listed as ‘glycans’ in the JSON format. Within this ‘glycan’ scope, information is segmented into glycan types, that is, ‘n-glycan’, ‘o-glycan’, ‘s-glycan’, ‘c-glycan’, and 'ligand'. Each of these glycan types contains an array of individual

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• both gave cyclized product 6a in 70% yield (Table 1, entries 3 and 4). An increase of the reaction time to 12 h did not improve the yield (Table 1, entry 5). The reaction was further evaluated in the absence of ligand which afforded the product in 35% yield (Table 1, entry 6). Screening of ligands, e.g

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

• low yield of the first approach. Replacing the catalyst and increasing the temperature or the amount of boronic acid proved to be unsuccessful. With entry 6 (Table 1) it was shown that similar yields could be obtained by removing the ligand and using higher amounts of catalyst. Therefore, no

• additional ligand was used in the next attempts. Additionally, it was observed that by replacing the less polar solvent by a mixture of a more polar solvent and water in a 5:1 ratio, yields could be significantly improved. Therefore, sodium hydroxide was used as the water-soluble base, which also proved to

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• benzenes that have more than one substituent; for example, the ortho-, meta-, or para- relative substitution of a disubstituted benzene should ideally be replicated in the saturated bioisostere to ensure ligand–protein binding is conserved through the bioisosteric swap. Bioisosteres of para-substituted

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• (Scheme 1) [20][21]. Vs NnlA contains a Per-Arnt-Sim (PAS) domain – protein domains that often bind heme and function as gas or redox sensors [20]. Indeed, Vs NnlA was shown to contain a heme cofactor [21]. Mutagenesis of a predicted histidine ligand to this heme resulted in loss of the heme and the

• [32]. We sought to identify the heme binding site, but AlphaFold does not model this. However, this AlphaFold model was predicted to bind a heme cofactor by the consensus modeling tool COACH [33]. This protein–ligand model exhibited steric clashes with the heme and protein side chains (data not shown

• ), limiting the use of this model to predict the heme environment. Nevertheless, this protein–ligand model heme binding between the β-sheet and an α-helix based on similarity to the oxygen-sensing dimeric DosH protein [34]. DosH is also a heme-binding PAS-domain containing protein, further validating the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• and 3 in Table 7). The reaction with only oxidized ligand (dppeO2) also works indicating that structure 103 could also be the active hydrochlorination complex (compare entries 4 and 5 in Table 7). The applicability of the reaction is confined to highly reactive 1,1-disubstituted or trisubstituted

• functional tolerance of this methodology is striking. Especially examples with sensitive aldehyde (175), nitrile (176), N-Boc (177), furan (178), thiophene (179), and even tertiary alcohols (180 and 181) are impressive. The primary drawback of this methodology lies in the synthesis of the ligand L3

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• depends on the relative configuration of the ligand used; cis-configuration of ligand affords the nitroaldols with major enantiomer S- (up to 97% ee), whereas the application of ligands with trans-configuration led to nitroaldols with major R-enantiomer (up to 96% ee). The “proline-type” ligand IV was

• ; Introduction The application of chiral metal complexes as enantioselective catalysts is among the fundamental strategies for preparing compounds in non-racemic forms [1][2][3][4]. These complexes typically comprise a chelating chiral ligand capable of coordinating with a metal ion; otherwise, a metal atom

• itself constitutes a stereocentre [4]. The specific pairing of a chiral ligand and a metal ion is essential for the catalytic characteristics and its effectiveness of the complex in asymmetric syntheses [1][2][3]. In recent years, our research group has synthesised a series of chiral ligands based on 2

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• started our studies with the palladium-catalyzed MCR of ethyl diazoacetate (1a), 1,3-butadiene (2a), and 1-phenylpiperazine (3a) in the presence of 5 mol % Pd(OAc)2 and 10 mol % Xantphos as ligand. To our delight, after irradiation with blue LED light in dimethylformamide (DMF) for 12 h at room

• experiments indicated that ligand, palladium, light and argon atmosphere were necessary for this transformation (Table 1, entries 2–5). Heating conditions could not facilitate the reaction instead of light conditions (Table 1, entry 6). The efficiency was maintained with another Pd(II) catalyst Pd(PPh3)2Cl2

• of the hybrid α-ester alkylpalladium radical generated from the diazo ester (Table 1, entry 10) [53]. Replacing Xantphos with rac-BINAP or DPEphos gave very low product formation, indicating that the type of ligand was crucial for this transformation (Table 1, entries 11 and 12). Changing the

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• -step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions. Keywords: annulation; carbene; gold

• secondary gold-ligand interactions [8][9][10], chiral environments [11][12][13] including those enabling secondary interactions with substrates for asymmetric catalysis [14], cooperative and bimetallic catalysis [7][15], and redox-enabling function for Au(I)/(III) cycles [16][17]. Such L-shaped ligands

• provide scope to influence the reactivity profile of their resulting metal complexes through steric shielding, direct stabilising interactions with the metal, or by proximal effects to reactive species. Given the sensitivity of metal catalysis to even subtle steric and electronic changes in the ligand

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• treatment of acute severe pain) [29] and an investigational drug NOP-1A (a ligand for the nociceptin/orphanin FQ peptide (NOP) receptor which is thought to be involved in several central nervous system disorders such as anxiety, depression, drug abuse, and seizures) [30]. A wide range of biological

• properties are exhibited by compounds based on a THF and THP core spiro-conjugated with the pyrrolidine ring. These frameworks are present in a number of synthetic biologically active compounds (such as NaV1.7 blocker XEN907 for the treatment of pain [31], σ1 receptor ligand 6 [32], histamine-3 receptor

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• particularly evident for metal complexes, where the system's geometry can be finely tuned to modulate its response based on the selection of metal and ligand components. This aspect has been extensively explored by Schmittel and co-workers in a recent review [17]. Molecular tweezers have been developed in this

• -workers introduced a switchable system based on a terpyridine (terpy) ligand (Figure 8), which is structurally similar to the diphenylpyridine units used by Zimmerman in rigid clips, but can change their conformation upon complexation by a metal cation [32][33]. When substituted at the 6 and 6" positions

• system and enable dynamic ligand formation due to the reversibility of the hydrazone bond formation [40]. More recently, Vives and co-workers have developed a family of terpyridine-based tweezers bearing metal–salphen complexes as functional units (Figure 9). Using metal complexes as arms brings

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• out under a variety of conditions with cationic gold catalysts supported by phosphine ligands. The impact of ligand on gold, protecting group on nitrogen, and solvent and additive on reaction rates was determined. The most effective reactions utilized more Lewis basic ureas, and more electron

• both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls. Keywords: alkene hydroamination; general acid catalysis; gold catalysis; isotope effect; phosphine ligand effect; solvent effect; Introduction

• undertaking a 1H NMR spectroscopic kinetic survey of solvent, ligand, and substituent effects on the general reaction 1 → 3 (with a variety of N-protecting groups), to supplement known qualitative observations. We found that, (1) electron-withdrawing phosphines accelerate hydroamination, (2) reactions are

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• previously described an activity-based protein profiling (ABPP) strategy for NRPSs using ABPs that target A-domains (Figure 2b) [13][14][15]. The probes comprise an aminoacyl-AMS ligand and a photoaffinity group with clickable alkyne functionality appended to the 2′-OH group of adenosine. A complex structure

• probes (AA-AMS-BPyne) can selectively label the A-domains corresponding to the amino acid of the ligand in both recombinant enzymes and proteomes. We recently reported that these probes can be used to label the A-domains of endogenous NRPSs in live bacterial cells [17][18][19]. The intracellular labeling

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• derivatives (Scheme 1b) [21]. In the course of this reaction 20 mol % of Pd catalyst, 50 mol % of phosphine ligand and 30 equiv of DBU as base were used to afford the desired fluoranthene derivatives. 1-Naphthylboronic acid and 1,2-dibromobenzene in the presence of Pd2(dba)3 (20 mol %) and PCy3 (80 mol

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• [20][21]. More recent approaches have leveraged photoinduced ligand-to-metal charge transfer to generate radicals from aliphatic [22] and aromatic [23][24] carboxylic acids. However, more broadly used approaches involve carefully designed activated esters. Barton esters 2 emerged in the early 1980s

• -halides [115]. Their optimized reaction conditions required a NiII precursor, 2,2’-bipyridine (bpy) as ligand, silver nitrate (AgNO3) as an additive and the combination of a magnesium (Mg) sacrificial anode and a RVC cathode (Scheme 35A). A crucial discovery in advancing this methodology was the in situ

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• binding in solution and a further confirmation of the binding specificity obtained by the array experiments. We note that the functional activity of bacterially produced CMA1 indicates that potential modification by glycosylation is not required for ligand binding. Next, we set out to quantify the binding

• arrangement of the ligand in the binding site (Figure 4c,d). While lectins such as CMA1 typically can present three binding pockets in their CBM13 domain, we hypothesized that the N-terminal half of CMA1 would in fact only exhibit two functional binding sites. However, only the alpha site was found occupied

• (BioRad). 0.6 mg/mL protein in PBS was mixed with SYPRO Orange (Sigma-Aldrich, Merck, #S5692) and glycan ligand (10 mM GalNAc; Carbosynth, #MA04390; 10 mM GlcNAc, Carbosynth, #MA00834; 10 mM blood group H type-2 tetrasaccharide; Elicityl, GLY032-2) in a total reaction volume of 25 µL. The temperature was

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• group was substituted by a mesyl substituent and BIPHEP was used as a model phosphine ligand instead of Tol-BINAP to reduce the computational cost. The calculations, conducted at the B3LYP-D3/cc-pVTZ-PP(SMD=o-DCB)//B3LYP-D3/cc-pVDZ-PP level (see full computational details in Supporting Information File

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• ; multi-step reactions; multicomponent reactions; one-pot synthesis; organocatalysis; tandem reactions; transition-metal-catalysis; The synthesis of pharmaceutical ingredients, natural products, agrochemicals, ligand systems, and building blocks for materials science has reached a high level of

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• (entry 1, Table 1). Next, the same procedure was carried out in the presence of molybdenum hexacarbonyl (Mo(CO)6, 2 equiv) as CO surrogate, under the previous conditions, but again we only observed the formation of intermediate 3a in 21% yield (entry 2, Table 1). Changing the ligand to triphenylphosphine

• effective ligand in a variety of highly efficient aminocarbonylation reactions with Mo(CO)6 due to its strong basicity and accelerated release of CO from this reagent [21]. The reaction was then screened using two different bidentate ligands, XPhos and XantPhos, and using the previous reaction conditions

• -step synthesis of DBDAPs, we embarked on an in-depth study of the B–H coupling/carbonylative cyclization in a step-wise fashion. Our first attempt was conducted using the previous conditions, which led to the desired compound 3a in 15% yield (entry 1, Table 2). Changing the ligand to PPh3 under the

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• wormlike nanoparticles. In rotaxanes, the utilization of metal–ligand bonding involving CuI is a common strategy for immobilizing a thread moiety within a macrocycle. However, the efficacy of such a bonding is compromised when catalysts are used in stoppering reactions, e.g., the copper-catalyzed azide

• –alkyne cycloaddition reaction. Consequently, a [2 + 2] CA–RE reaction that can yield push–pull chromophores without the use of a catalyst is exceedingly valuable as a stoppering method, even for systems featuring metal–ligand bonding. Accordingly, Diederich et al. demonstrated the synthesis of a CuI bis

• room-temperature solution (dichloromethane) and as a frozen matrix at 77 K [123]. This is in contrast with the typical homoleptic phenanthroline-based CuI complexes renowned for their emissions from a triplet metal-to-ligand charge transfer excited state. The absence of luminescence may be attributed

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

• organic solvents (78–20% in MeCN). The quinolizinium derivatives bind to DNA by intercalation with binding constants of 6–11 × 104 M−1, as shown by photometric and fluorimetric titrations as well as by CD- and LD-spectroscopic analyses. These ligand–DNA complexes can also be established in situ upon

• 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

• efficient fluorescence quenching (Figure 5), which is commonly observed with this class of cationic ligands [3][70], mainly as a result of a photoinduced electron transfer from the excited, DNA-bound ligand with the DNA bases [71]. The binding isotherms obtained from the titration data were used to

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• Bremen, Germany 10.3762/bjoc.20.2 Abstract N-Acyl carbazoles can be efficiently produced through a single-step process using amides and cyclic diaryliodonium triflates. This convenient reaction is facilitated by copper iodide in p-xylene, using the commonly found activating ligand diglyme. We have

• [33][34]. Results and Discussion Initially, we investigated the synthesis of N-acyl carbazole by treatment of diaryliodonium salt 1a with valeramide using Cu(I) catalysts [18]. The results are shown in Table 1. In the first experiments in p-xylene at 120 °C with DMEDA as N,N-ligand, only modest