Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• . Results and Discussion First, optimization of the reaction conditions was conducted using substrate 1a as a model according to Table 1. The molar ratio of 1a, the catalyst, the base, and the ligand used in Table 1, entry 1 was adapted from the literature [25]. The reaction mixture was stirred for 5 h at

• show the presence of the product 2a, but it showed the presence of 91% of the starting hydrazone (Table 1, entry 8). To evaluate the effect of the base, K3PO4 or Cs2CO3 was used, but the yield was lower than 60% (Table 1, entries 9 and 10). The influence of the catalyst/ligand molar ratio (Table 1

• ligand (Table 1, entry 22), but the product could not be detected by TLC analysis. In order to compare the efficiency of the optimized conditions with the one-pot approach, a reaction was carried out starting from o-chlorobenzaldehyde and phenylhydrazine under the conditions shown in Table 1, entry 3

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• associated biological activities and relevance to the naturally occurring alkaloids [1], 1,4-dihydro-3(2H)-isoquinolones (1,4-DHIQs) undoubtedly represent a privileged scaffold [2] for drug design considering such diversely bioactive compounds documented in the literature as ligand for serotonin 5-HT1A

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• tumor necrosis factor-α (TNF-α) and C–C motif chemokine ligand 2 (CCL2) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, using NF-κB inhibitor BAY-11-7082 as the positive control. Compound 3 displayed promising dose-dependent anti-inflammatory activity with the inhibition

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• intermediate A to form a π-complex B, and a ligand exchange reaction from B occurs to produce intermediate D, together with the elimination of selenol C. The selenol C is oxidized to diselenide 2. Finally, the intermediate D undergoes a reductive elimination to form the desired product 4, with the regeneration

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• halides in a test tube [15]. They found that a Pd(dba)2/DPEphos catalytic system was effective for aryl bromides, and aryl chlorides reacted more efficiently when XPhos was used as the ligand [15]. Although their achievements are remarkable, this protocol is only applicable to liquid substrates, which can

• ). When the reaction was stopped after 5 min, only a 26% yield of 3a was obtained (Table 1, entry 2). The use of 1,1'-bis(diphenylphosphino)ferrocene (dppf), which is the optimal ligand under the original conditions for the solution-based protocol [8], provided only trace amounts of 3a (1%, Table 1, entry

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• Fe(III)-OH species can be exchanged with the solvent water [76]. Therefore, the fact that almost all of the oxygen atoms in the Fe(III)-OH species exchanged with the solvent in the enzyme reaction of NvfI suggested the presence of a long-lived C3' radical and the hydroxy ligand during the reaction

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• ; N-halosuccinimide; palladium(II); Introduction Electrophilic aromatic substitution [1][2][3] and ligand-directed transition-metal-catalyzed reactions [4][5][6][7][8] are among the most widely used synthetic approaches for the preparation of halogenated arenes. They are important precursors in cross

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• from supramolecular protocols in catalysis [9]. Metal–ligand-based 2D and 3D self-assembled architectures have been extensively studied over the past decades [15][16][17][18][19][20][21]. While in the early years, the focus has been on the exploration of structural features, more recent advancements

• have led to a multitude of extremely useful functional applications (molecular recognition, ion sensing, catalysis, etc.) [9][22]. Since most of these structures are homoleptic in nature, i.e., they are constructed from a single type of ligand [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19

• multicomponent ATP synthase motor [23], a more detailed and refined configuration of purposeful machinery [24]. For the preparation of heteroleptic aggregates, one must differentiate between dynamic (rapidly exchanging) and kinetically inert heteroleptic metal–ligand interactions. While the inert heteroleptic

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

• ]. The template complex (S)-3 was assembled by mixing the macrocycle (S)-1 (containing both a phenanthroline ligand and a BINOL unit) with [Cu(CH3CN4)]PF6 and the acyclic phenanthroline precursor 2. Then, the BINOL-based diiodide (S)-4 and Cs2CO3 were added successively over 18 hours. This resulted in

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• (Scheme 24). Tang and co-workers described the synthesis of thiosemicarbazone 80 from menadione (10) through a condensation reaction with thiosemicarbazide (79), which was used as a ligand in the synthesis of metal complexes using different transition metals, in refluxing ethanol (Scheme 25) [125

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• , the approach presented herein avoids the use of the significantly more expensive reagents such as the arylboronic acid derivatives and the (t-Bu)3P ligand. To add to that, the latter is also highly air sensitive and thus requires special handling, but it is essential for a reasonably efficient Pd

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• metallic ions depends on the presence of suitable ligand groups. Hydroxamates, 2,3-dihydroxybenzoates, and α-hydroxycarboxylates make excellent bidentate ligand groups, as their negatively charged oxygen atoms can maintain strong interactions with ferric iron [3]. But there are also many siderophores

• featuring ligand groups with nitrogen or sulfur as donor atoms [4]. The siderophore–iron complexes are recognized by highly selective microbial transporters. Following their translocation into the cell, the bound iron is released via a reductive or hydrolytic mechanism [2] Members of the genus Nocardia are

• structural features of these molecules. Amamistatin B (5) exhibits three bidentate ligand groups and can thus form an octahedral complex with ferric iron. The removal of one of these groups (e.g., the hydroxamate function at the ε terminus of the lysine residue) already leads to a considerable loss of iron

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• structures endowed with catalytic features are full covalent units (e.g., cyclodextrins, cucurbiturils, pillararenes and other derivatives) whose synthesis can be sometimes time consuming. Alternatively, supramolecular catalysts can be obtained through self-assembling units [18][19], metal-ligand components

• tetrahedral polyanionic metal-ligand capsule as supramolecular catalyst, observing lower catalytic activity and product distribution favoring isopulegol but also with large amounts of neoisopulegol and neoisoisopulegol (52%, 32% and 11%, respectively) [51]. More favorable selectivity towards isopulegol was

• obtained by the same group with a larger tetrahedral capsule using pyrene in place of naphthalene units observing isopulegol, neoisopulegol and neoisoisopulegol with 71%, 24% and 4% selectivity [52]. The comparison between the metal-ligand tetrahedral capsules and the H-bonded 16 shows a common trend of

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• environment inside the container. The containers include supramolecular structures self-assembled through metal/ligand interactions or hydrogen bonding and open-ended covalent structures such as cyclodextrins and cavitands. Challenges and prospects for the future are also provided. Keywords: confinement

• accommodated in the cavity of A through π–π stacking interactions between the naphthalene ring of 3 and a triazine ligand of A from the X-ray crystallographic analysis. In the control experiment, without host A, only 44% yield of the conventional 9,10-adduct 4 was produced without any 1,4-adduct product

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• of water to the minimum necessary to solubilize the copper sulfate. Thus, performing the reaction in toluene/water 100:1, ketimine hydrolysis was almost entirely prevented and the yield of compound 2a raised to 52% (Table 1, entry 6). With regard to the ligand (Table 1, entries 7 and 8), PPh3 behaved

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• [Pd(C3H5)Cl]2 and ligand L1 (Scheme 2) [11]. The reaction, that could also be considered as Friedel–Crafts type, intramolecular allylic alkylation, delivered nine-membered ring bearing 3,4-fused indoles 2 in moderate to good yields. In the asymmetric version of the reaction catalyzed by [Ir(cod)Cl]2

• (4 mol %) and ligand L2, the ring closure also took place regioselectively at the indole C3 position, albeit the products 3 were embedded with a seven-membered ring instead of a nine-membered one. The absolute configuration of products 3 was proposed to be S, based on the general rule of

• diastereo- and enantioselectivities (up to >20:1 dr and >99% ee) (Scheme 8) [18]. The optimized reaction conditions for the annulation reaction were as follows: [Ir(cod)Cl]2 (4 mol %), Carreira’s P/olefin ligand (S)-L3 (16 mol %), Zn(OTf)2 (100 mol %), and 4 Å MS in CH2Cl2 at rt. The synthetic protocol

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• ligand 2,2’-bipyridyl (Scheme 1). The reaction utilizes KOH as the base, since it provides the suitable deprotection of arylynols 3 during the synthesis of the terminal arylalkynes. The optimized conditions revealed that 10 mol % of Fe catalyst/ligand at 140 °C for 48 h afforded the maximum yields of the

• steric effects. Anilkumar and co-workers reported an iron-catalyzed Sonogashira coupling of aryl iodides with terminal alkynes in the presence of a catalytic system made up of the greenest solvent, water, in the presence of 10 mol % FeCl3·6H2O and 20 mol % 1,10-phenanthroline as ligand under aerobic

• , but their efficiencies were found to be lower than that of 1,10-phenanthroline. Metal impurities in FeCl3·6H2O were detected by using ICP mass spectrometry. Lipshutz and co-workers prepared nanoparticles from inexpensive iron(III) chloride containing reusable palladium in ppm level and XPhoS as ligand

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• dummy ligand present on the active iridium species, tetrabutylammonium salts were added (Table 1, entries 4 and 5); however, these were not as efficient in the reaction. Other iridium sources (Table 1, entries 2 and 3) proved to be not as effective in promoting the reaction, with Vaska’s complex failing

• its derivatives were used in all calculations rather than the experimentally used precatalyst [Ir(COD)Cl]2, as ligand exchange with the hydroxide ions present likely generates the [Ir(COD)OH]2 species in solution. Upon monomerization of [Ir(COD)OH]2, either through solvolysis or coordination of the

• over endo-η2-coordination, as the less congested convex face would impose reduced steric requirements. There are two potential isomeric intermediates following η2-coordination to the exo-face of MeOBD concerning the relative orientation of the COD ligand, acyl group, and C1-substituent on the

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• phosphine ligand implanted on the aromatic ring (entry 5, Table 1). Interestingly, this effect was substantially improved with the use of the calix[6]arene-based complex C(AuCl)2 (entry 6, Table 1). Overall, the ortho-substituted macrocycle C(AuCl)2 displayed an enhanced selectivity, with respect to the

• ’, 69%); ii) (Me2S)AuCl in DCM, 0 °C to rt (A’(AuCl), 94%; B’(AuCl), 92%; C’(AuCl), 96%). Ligand effect in gold(I)-catalyzed cycloisomerization of 1a. Supporting Information Supporting Information File 18: Experimental procedures, characterization data of compounds and copies of NMR spectra

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• Pd source together with the water-soluble Buchwald ligand sulfonated SPhos (sSPhos) and potassium fluoride as a base. The reaction was performed in a solvent mixture of dimethoxyethane, ethanol and water (DME/EtOH/H2O 9:9:2) at 120 °C under microwave irradiation for 30 min (Scheme 1) [78]. The

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• diphosphine ligand. Preliminary results demonstrated the chiral iron species moderately controlled the enantioselectivity of the aryl Grignard cross-coupling. This work provided a proof-of-concept towards the use of vinylcyclopropanes as useful 1,5-synthons in asymmetric Fe-catalyzed cross-coupling reactions

• ligand and its appropriate steric properties are thought to be crucial to the success of the reaction [71]. The authors showed the in situ-formed 1,3-dienylmagnesium species 33 can also be trapped by a variety of electrophiles, demonstrating the synthetic utility of the reaction. In 2016, Fürstner and

• to trisubstituted (E)-alkenylboronates 55, acting as a 1,5-synthon, similar to Gutierrez‘s vinylcyclopropanes (Scheme 4) [66]. Based on mechanistic investigations, Koh proposed the catalytically active iron-boryl species 57 is generated through the ligand exchange of 56 with B2pin2 which can undergo

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• influence of the strength of the ligand and the metal cation sphere (together with small molecules coordinated in its outer sphere) are crucial points to study the structure–activity relationship (SAR) onto a fixed biological target [10][11][12]. In particular, N-benzoylthiourea derivatives are versatile

• , antitumoral, antimalarial, antifungal, or antiviral activities [14]. In this study, as a continuation of our work related to organometallic compounds with very low/modest amphiphilic character [15][16][17], we propose the incorporation of a 3-indolylmethyl group in the ligand and compare the bioactivity

• ligand rotamers were considered during the optimization process. Only one enantiomer was selected for running the calculations for simplicity. The obtained results are gathered in Figure 1 and Figure 2. These calculations show that for ligands L1 and L3, conformer A and conformer B, resulting from a free

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• be prepared by asymmetric C–H activation. The C–H activation or functionalization can be achieved by a metal-catalyzed chiral phosphoric acid ligand-assisted method, which offers distinct possibilities to provide various chiral biaryl compounds by changing different directing groups (DGs) [46]. Since

• density functional theory calculations [46]. Recently, Shi, Lin and co-workers reported the atroposelective synthesis of axially chiral biaryls by Pd(II)-catalyzed free amine-directed atroposelective C–H olefination using chiral spirophosphoric acid CPA 5 as an efficient ligand and Ag2CO3 as the oxidant

• interactions with the substrates. Moreover, the SPA ligand loading of 1 mol % is effective for this reaction under mild conditions [50]. Moreover, Shi, Lin and co-workers reported the first Pd(II)-catalyzed directed atroposelective C–H allylation of 2-(naphthalen-1-yl)aniline derivatives 14 with methacrylates

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• 43 Prague 2, Czech Republic 10.3762/bjoc.17.179 Abstract The stereoselective Suzuki–Miyaura cross-coupling of (Z)-β-enamido triflates is demonstrated. Depending on the nature of the ligand in the palladium catalyst, either retention or inversion of the configuration during the synthesis of β,β

• (Z)-β-enamido triflates could, during the Suzuki cross-coupling, undergo isomerization of the double bond, similarly to enones, and thus serve as starting materials to either (E) or (Z)-isomers of enamides depending on the conditions used. Here we present a study of the effect of ligand on the

• configuration of the double bond were formed preferably. Both conditions were applied to a range of arylboronic acids and (Z)-β-enamido triflates. A: Synthesis of (Z)-β-enamido triflates and subsequent stereoselective cross-coupling reactions. B: Ligand-controlled stereoselective synthesis of β,β-diaryl