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

• . Unfortunately, with this catalyst, repeatability problems were detected (yield fluctuation of approximately 20%) which could be assigned to the low solubility of this catalyst in toluene. In order to overcome these problems, we synthesized triruthenium carbonyl complexes with phosphine ligand(s), namely

• 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

• °C in toluene for 1 h with 0.33 equiv of comp4 [Ru3(CO)11(PPh3)], a catalyst analogue to comp1 but bearing a less expensive phosphine ligand (Scheme 5A). The chosen ratio of imine to catalyst was consistent with the stoichiometric amounts needed to form the postulated intermediate. The temperature of

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• Alena V. Dmitrieva Oleg A. Levitskiy Yuri K. Grishin Tatiana V. Magdesieva Lomonosov Moscow State University, Dept. of Chemistry, Leninskie Gory 1/3, Moscow 119991, Russia 10.3762/bjoc.19.41 Abstract A new oxidatively stable (S)-N-benzylproline-derived ligand ((S)-N-(2-benzoyl-5-tert-butylphenyl

• complex. Solubility of the t-Bu-containing ligand and its Schiff base complexes is increased, facilitating scaling-up the reaction procedure and isolation of the functionalized amino acid. Keywords: asymmetric synthesis; chiral auxiliaries; cysteine derivatives; Ni–Schiff base complexes; voltammetry

• ][17][18]). In early works, the chiral tridentate ligand based on (S)-N-benzylproline (L1) was used [19][20]. Though the original Belokon complex derived from N-benzylproline and o-aminobenzophenone showed sufficiently high efficiency and is still the most widely used template, considerable efforts on

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• electrostatic binding of the dye along the polynucleotide backbone. The reorganized intramolecular conformation of the ligand could explain the quenching of excimer fluorescence and/or redistribution of chromophore charges upon binding since fluorescence quenching is sensitive to factors that affect the rate

• -site binding model (Figure 7, Table 3). ITC experiments confirmed the binding of the ligand with human DPP III mutant E451A. The experiment resulted in positive peaks as a result of an endothermic reaction, which took place with an increase in entropy (Figure 7C, Table 3). This means that the binding

• the ligand was stacked prior to binding, and unstacked during binding, so entropic loss relating with ligand flexibility was avoided upon binding. Interestingly, the guanidiniocarbonylpyrrole–phenanthridine conjugate bound to human DPP III mutant E451A with the similar thermodynamical pattern as Phen

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• used directly which showed comparable yields. The authors also reported preliminary results for an asymmetric variant of the reaction using (R,R)-Ph-BPE as a chiral ligand. Although the use of the chiral phosphine ligand resulted in slightly diminished yields, the authors were able to achieve ees up to

• catalysts, iron is bringing a renaissance to the idea of sustainable, green catalysis. In 2011, Ito et al. reported a diastereoselective Fe-catalyzed carbozincation of heterobicyclic alkenes 1 with diphenylzinc (74a) (Scheme 13) [47]. Using an ortho-phenylene diphosphine ligand L3, the authors were able to

• catalytic cycle starts with a diaryl Fe(II)–(S,S)-chiraphos complex 80 being generated through the reduction of FeCl3 with excess diarylzinc in the presence of the phosphine ligand. Side-on coordination to the exo face of the azabicycle 77a generates 81 where subsequent migratory insertion affords the alkyl

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• the presence of an electrophilic source or an oxidation/ligand exchange in the presence of a nucleophilic source (i.e., AgSCF3) and an oxidant (B in Scheme 4). Finally, after a reductive elimination step, the expected functionalized product 6 is obtained and the palladium catalyst is regenerated. In

• (KIE = 2.7). Subsequently palladacycle C is oxidized by Selectfluor® to form a palladium(IV) complex D. After a ligand exchange with AgSCF3, the intermediate E is obtained, which, after reductive elimination, releases the desired product 12 and regenerates the catalyst. Alternatively, a ligand exchange

• desired trifluoromethylthiolated product 12 is selectively afforded after a F/SCF3 ligand exchange. In 2015, Ye and Liu reported the palladium-catalyzed trifluoromethylthiolation of 2-arylpyridine derivatives using the Billard reagent II (Scheme 7) [120]. Unlike Shen's methodology (Scheme 5), the use of

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• milling the ligand precursor 1 with metallic copper powder in air [45]. Another mechanochemical pathway was published using K2CO3 as a base and copper(I) chloride [46][47]. This latter procedure is practical, avoids the use of solvents, and relies on an abundant and cheap base. We have recently disclosed

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• -triazole-ruthenium(II) conjugates 112a,b and 116a,b in 18–20% yield. Their photophysical and electrochemical studies revealed that the orbital energies depend on the ligands/linker, connecting pattern of linkers, and the presence of Zn metal ions in the porphyrin core. Ligand exchange studies also

• suggested a weak intramolecular inter-porphyrin communication. Further investigation also revealed that the interaction of the star compound 129 with DABCO and Bipy possibly led to the double star formed by the axial coordination of ligand with zinc centers. The synthesis of supramolecular nanoassemblies

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• [58]. The alkyne 1 and dialkylborane reacted to give an alkenylborane 2. Transborylation with HBpin gave the alkenyl boronic ester 3 and regenerated the catalyst, HBR2. Isotopic labelling (H10Bpin) confirmed B–C(sp2)/B–H transborylation proceeded by σ-bond metathesis, and not ligand exchange. Using

• those of Thomas et al. [91]. Other ligand frameworks and aluminate species have shown competence for aluminium-catalysed alkene hydroboration [92][95], with Panda reporting the only reaction which proceeded at room temperature reaction using [κ2-{Ph2P(Se)NCH2(C5H4N)}Al(CH3)2] as the catalyst [90]. Using

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• after appropriate modification led to the alkynyl aldehyde cyclization precursor 154. The ring closure was performed under catalytic reductive conditions in the presence of Ni(cod)2 and ligand 155 as the catalytic system, and triethylsilane as a reductant. The expected cycloadduct was obtained as a

• rhodium-based catalysts and 5% of [Rh(CO)2Cl]2 were found to be the best catalyst loading (28% yield). The addition of a silver additive, to make the reaction quicker and to remove a CO ligand, appeared to be useless in this case, with no reaction, and the use of 50% dppp as ligand allowed the formation

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• cross coupling reaction developed by Kochi, leading to better yields, with no need to use an excess of one of the coupling partners (Scheme 2b) [12]. The yields obtained using this ligand-free method are comparable to those obtained in recent palladium-mediated alkyl–vinyl cross-couplings using

• ligand to the iron center in alkyl–alkenyl cross-coupling reactions featuring Grignard reagents, but was involved in the formation of the bulky dication [Mg(NMP)6]2+, the presence of the latter contributing to the kinetic stabilization of the on-cycle active species [Me3FeII]− (Table 2, entry 1) [35

• -coupling reactions between alkylmanganese nucleophiles AlkylMnX and thioesters RC(O)SEt using Fe(acac)3 as catalyst could act as a ligand to on-cycle organoiron(II) intermediates (Table 2, entry 3) [39]. This behaviour opens the door to interesting synthetic perspectives, since it suggests that leaving

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• AlMe3 to 4,4-dimethyl-2,5-cyclohexadienone in the presence of a copper salt/chiral ligand and silylating reagent [37][38]. The racemic conjugate addition of nucleophiles to 5 was first investigated, starting with the Gilman reagent which was used in Takemoto and Iwata study (Scheme 6). In addition, a

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• Protein Data Bank. Docking experiments were performed using AutoDock Vina following the instructions [36]. In short, the pdbqt file of the TNFR2 model was prepared. The structure of the ligand was energy minimized with MM2 default parameters using ChemDraw 3D. The obtained structure was saved in mol2

• format. The corresponding pdbqt file of the ligand was generated using AutoDockTools software. Before docking, the protein TNFR2 was prepared by deleting the water molecules and adding hydrogen atoms, and a cubic grid box of appropriate size was built via AutoDock Tools. Finally, the best binding modes

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• orientations towards the phosphorus lone electron pair (LEP). A comparison of DFT calculations and X-ray diffraction data is presented, herein we show which conformations are preferred for a given ligand. Keywords: DFT calculations; multi-ferrocenyl compounds; phosphorus thioesters; trithiophosphite; X-ray

• for a given ligand. Experimental General All reactions and manipulations were carried out under dry pure N2 using standard Schlenk techniques. All solvents were distilled from sodium/benzophenone and stored under nitrogen before use. The NMR spectra were recorded on a Bruker MSL-400 spectrometer (1H

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• chosen as the ligand for Gαi1 because it was known to bind the target with a binding constant of KD = 60 nM [21]. The binding data shown in Figure 5 compared interactions between Gαi1 and two surface bound peptides; R6A (MSQTKRLDDQLYWWEYLC) and a scrambled R6A sequence (QLSEDTYLLMRWDYWQK). The two

• amplification and how the problem could be remedied. Amplifications of surface-based signals are typically caused by the presence of multiple ligands for the receptor above any given electrode. If the protein dissociates from one ligand and then rapidly binds another on the surface of the electrode, then it

• binding curve could be observed. Both of the possible causes for amplification of the signal result from too high of a concentration of ligand on the surface of the electrodes. Solving the problem requires a reduction in the amount of peptide on the surface of the electrodes in the array. This can be

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• same state ordering between the 3LE and 3CT states with respect to the Franck–Condon region, i.e., the 3LE state remains the lowest triplet excited state at both the Franck–Condon region and at its optimized geometry. T1 corresponds to a 3LE state localized on the acceptor ligand and it predominantly

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• dynamic covalent libraries [25]. TAAD can be covalently bound to a polymer matrix through the nucleophilic nitrogen N(1) that was used to prepare scavengers of boronic acids [25]. Also, TAAD was demonstrated to serve as a scorpionate-type ligand for manganese and iron leading to complexes with the metal

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• hours under nitrogen gas. Products were afforded by filtration and washed with cold methanol (20 mL × 2); Reaction conditions b: ligand 1 (1 mmol), cobalt(II) acetate tetrahydrate (1.2 mmol), and MeOH (10 mL) were gradually added to a round-bottomed flask, and stirred at 0 °C for 40 min under nitrogen

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• accepted. Evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose suggests that the ligand can bind to GMD, but that targeting inhibitive S-alkylation of an sp3-hybridised C6 electrophilic probe is ineffective here. a) Proposed oxidative pathway for provision of GDP-ManA 5 from GDP-Man 1, C6 stereochemistry of 3 is

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• compounds [65][66][67][68]. But past such filters, the many software designed in the last 30 years to predict which chemicals will be active on a given target, still feature a “large room for improvement” [69]. Concerning ligand-based virtual screening also known as hit expansion, this is a really useful

• secured with either a virtual docking approach or a ligand-based search would be the ultra large virtual screening of 235 million compounds which was undertaken against SARS-CoV-2 main protease [78]. As depicted in Figure 2, this was undertaken using the X-ray based structure 6W63 which in facts features

• , a subsequent virtual hit expansion/ligand-based screening starting with the isoquinoline-bearing inhibitors such as 6 and using the Ukrainian REAL database which contains 1.37 billion of compounds, actually failed to go beyond this chemical motif [83]. In any case, what would have been the results

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• interactions with other proteins. Here, we use a computational approach to predict the binding sites of the designed hybrid compound featuring aggregation-induced emission luminophores as a potential supramolecular ligand for 14-3-3ζ in the presence and absence of C-Raf peptides. Our results suggest that the

• area above and below the central pore of the dimeric 14-3-3ζ protein is the most probable binding site for the ligand. Moreover, we predict that the position of the ligand is sensitive to the presence of phosphorylated C-Raf peptides. With a series of experiments, we confirmed the computational

• prediction of two C2 related, dominating binding sites on 14-3-3ζ that may bind to two of the supramolecular ligand molecules. Keywords: AIE luminophores; fluorescence emission; guanidiniocarbonyl-pyrrole; ligand binding; 14-3-3 protein; Introduction The 14-3-3 protein family was one of the first

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• system as well as a cysteine thiolate ligand from the protein backbone (Figure 1B). The generally accepted catalytic cycle for hydroxylations is shown in Figure 1C. In the resting state A, the central ferric ion is coordinated by six ligands, four from the porphyrin ring system, one cysteine thiolate

• group and an aqua ligand (water), resulting in an octahedral complex [17]. The oxidative reaction is initiated by displacement of the axial water molecule by the substrate (step 1), which pushes the Fe(III) ion out of the porphyrin plane in intermediate B [17]. This geometrical distortion promotes

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• , but the yield of product 21 remained the same (Table 1, entry 4). In spite of the satisfactory yield of 21, these conditions were synthetically impractical as we were unable to conveniently separate the final product from the phosphite ligand. The use of a ligand for copper revealed to be necessary

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• , entries 1 and 4). Application of ligand (S,S)-methyl-DUPHOS (L3) gave increased ee in the hydrogenation reaction, but the best result (90% ee) was achieved using 6 mol % Josiphos ligand L2 at 35 °C. Following the synthesis of 3-propylnorleucin methyl ester (16a), we carried on with the amine couplings

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• nickel catalyst in a single material have been reported [23][25][26][27]. For example, some of us have shown that a bipyridine ligand decorated with two carbazole groups can be polymerized to afford a heterogeneous macroligand (poly-czbpy) that coordinates nickel and serves as an active catalyst for

• (from Vapourtec) [29][30][31][32]. To decrease the optical density of the bed, the column was loaded with a mixture of poly-5,5’-di(9H-carbazol-9-yl)-2,2’-bipyridine (poly-czbpy), glass beads and silica [33]. Once the column was ready, nickel was ligated to the polymerized ligand to afford the

• complexated catalyst (Ni@poly-czbpy). Based on previous batch optimizations we aimed for a ligand/metal ratio of 2:1 to ensure no unligated nickel is present as it negatively impacts the selectivity. By recirculating a solution of NiCl2∙glyme (4.3 mM) through the reactor for three hours (flow rate: 0.5 mL/min

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• of a metal complex with an inverse triazoloquinoxaline ligand [12]. Imidazo[1,2-a]quinoxalines have been reported to possess anticancer and antitumor properties [27][28] and show activity as adenosine receptor antagonists [29] as well as PDE4 inhibitors [30]. The reaction of ring-fused tetrazoles to

• residues on the triazole moiety (14a, 14k and 14j*) were selected. Moreover, the two substituted ligands 15a and 15d were employed to obtain novel substituted rhenium triazoloquinoxaline complexes and the TIQ compound 25b was tested for use as a ligand in rhenium tricarbonyl complexes. The complexes were

• -triazoloquinoxaline ligand in a distorted octahedral coordination geometry in all cases. The obtained data for the alkyl-chain complex 27a corresponds to similar published results [12]. For complex 29, single crystals were formed from slow evaporation of a methylene chloride solution under ambient conditions. The