Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• reactions have the advantages of high atom economy, simple operation, clean and green, and have become a research hotspot [31][32][33][34][35]. Cyclometalated iridium complexes with good catalytic efficiency and selectivity are very effective catalysts in ADC reactions. Moreover, these catalysts are easy to

• secondary alcohols 2 that allowed for the efficient synthesis of a series of quinolines 3 (up to 95% yield and >99:1 selectivity) (Figure 2). A preliminary evaluation of the compounds’ potential antibacterial activity was also performed. Results and Discussion We started our research with the ADC reaction

• the other hand, when no catalyst was added to the reaction system under the above conditions, the reaction also proceeded, but the chemical selectivity and yield were significantly lower (Table 1, entry 7). In order to obtain optimal conditions, the bases, reaction medium, and temperature were also

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

• array because it is the nature of those molecules that defines the biological interactions that can be studied [10][11]. As discussed below, such efforts need to not only control the selectivity of the reactions for specific, predetermined sites on the array, but also control the surface concentration

• complex molecule, the synthesis of a complex, two-dimensional addressable surface requires a new type of selectivity – "site-selectivity". The use of electrosynthesis is essential for obtaining this selectivity. With the substrate on the surface of the array, a hydroquinone/quinone redox couple was then

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• substrate(s) and potentially the transition state is essential in supramolecular catalysis. Supramolecular catalysis finds inspiration in natural enzymes, which show catalytic features such as substrates and products selectivity, efficiency, geometric control, and acceleration of chemical reactivity [1]. If

• catalysts were designed that showed substrate selectivity, turnover, regioselectivity, and stereoselectivity [5][6][7][8][9][10][11][12][13][14]. Supramolecular architectures with an internal cavity are potential candidates to work as supramolecular catalysts [5][6][7][8][9][10][11][12][13][14]. The first

• whose geometry, in low-polarity solvents, is controlled by the 1,2,3-alternate conformation of the calix[6]arene skeleton. These catalysts can tune the selectivity of the catalytic cycloisomerization of 1,6-enynes in response to the relative orientation of the coordinated gold(I) atom with respect to

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

• -aryloxy alcohols were thereafter synthesized through the KR of epichlorohydrin with different phenols using chiral Co–salen catalyst 2f (Table 3). meta-Substituted methylphenol showed less reactivity and selectivity (Table 3, entry 2), while tert-butyl monosubstitution at the para-position on the phenol

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

• chances of being identified in the course of screenings. In 2004, the Molecular Library Initiative sponsored by the NIH also tried to address such issues and provide probes to determine the function and therapeutic potential of all the human genes. Aside from considerations on the selectivity and drug

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• that are different from those found in solution. Computational studies have been a key to understand the role of mechanical force in such reactions and to explain the changes in selectivity under force [42][43][44]. For example, experimental results have demonstrated that ball milling in a planetary

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• . Under these experimental conditions, we did not detect the formation of the sulfonamide derivative, preserving complete selectivity towards the target formamide (Table 2, entry 4). Remarkably, the results remain unchanged regarding yields and purity by shortening the reaction time (Table 2, entry 5

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

• (BINAP)-assisted hydrogenation with H2 pressure up to 50 bar was also found to be ineffective. By changing the metal complex to Rh(COD)2BF4, we successfully realized the saturation of the double bond. Chiral ligands (R)-BINAP (L1) and (R,R)-phenyl-BPE (L4) gave unsatisfactory selectivity (Table 2

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• proposed based on computational results and the main product is formed favorably following the PES via the lowest ΔG# pathway in both the gas-phase and an ethanol solvent model. DFT calculations showed that kinetic selectivity is more significant than thermodynamic selectivity for forming main products

• IS5, in good agreement with the experimental results. Besides, the kinetic selectivity is more significant than the thermodynamic one for forming the main product 10ab with a rate constant ≈ 103–106 times higher (from the first step to the final step) in ethanol solvent (also in chloroform, DMSO) as

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

• 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

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• reactions (Figure S1, Supporting Information File 1). Due to the high reaction selectivity that the enzyme active site offers, these enzymes provide biocatalytic means for the biaryl linkage formation, and recent enzyme engineering efforts also demonstrated selective and efficient production of unnatural

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• with Ru catalyst (Table 3, entry 3). Similarly, both 2a and 3a were obtained with Ir and Pt catalyst (Table 3, entries 4 and 5). In particular, 3a was obtained preferentially with the Ir catalyst. These results revealed that the cathode catalysts strongly affected the selectivity between 2a and 3a. Pd

• was the best catalyst for the selective synthesis of 2a, and Ir catalyst should be suitable for the formation of 3a, regarding the current efficiency and selectivity (Table 3, entry 4). We also observed reaction profiles of the hydrogenation of 1a with the use of a Pd/C and Ir/C cathode catalyst

• the circulating system until 1a was consumed, the ketone 2a, obtained by the exclusive reduction of the C=C moiety, was obtained in 81% yield with a chemoselectivity of 92%. Similarly, cyclopentanone 2b was obtained from the corresponding enone 1b in 74% yield (88% selectivity). Substituted

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• good yields [29]. In this reaction system, the use of a quasi-divided cell enabled DMF to be oxidized with high selectivity at the anode even in the presence of carboxylate and bromide ions, which would generally be oxidized more easily than DMF. Accordingly, we tried this electrolysis system using a

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• secondary amines), carboxylic acids and isocyanates. Besides, an interesting reduction selectivity was observed. Exploration of the reaction process shows that it undergoes a two-step pathway via a formamide intermediate and the reduction of the formamide intermediate to monomethylamine as the rate

• by step-by-step methylation. Employing the mono-methylated products 1c and 8c, N,N-dimethylamine 6c and 12c can be obtained, respectively, via repeating our synthesis procedure. In order to understand the reduction selectivity of the method, the substrates bearing acetamide groups (19b and 20b) were

• reduction, and our method showed interesting reduction selectivity. To gain some preliminary insight into the reaction process, two representative intermediates for the synthesis of aliphatic methylamine 1c and aromatic methylamine 8c had been isolated and identified as corresponding formamides (see

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• of N-halosuccinimides (NXS, X = Br, I, and Cl). It was observed that PEG-400 plays a key role in controlling the reactivity of the substrates and to afford better regioselectivity. Almost exclusive para-selectivity was observed for the aromatic substrates with free o- and p-positions for mono- and

• in good yields (product 2ai and 2aj, Scheme 3). It is worthy to note that PEG-400 as the grinding auxiliary not only expedited the reaction but also played a key role in availing better regioselectivity. A very high para-selectivity was observed for both phenols and aniline substrates with free o

• observed in the case of salicylic acids or anthranilic acids leading to 2,4,6-trihalo derivatives when 3 equiv of NXS were used. PEG-400 plays a key role for faster reaction kinetics and to afford better regioselectivity. Almost exclusive p-selectivity was observed for the aromatic substrates with free

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• recycle them, good stability, low flammability, good solubility ability for many molecules, salts and gases, the possibility to use them as reagents and/or solvents, large electrochemical window, good electrical conductivity, their ionic nature sometimes increases the reactivity and the selectivity of

• as slow rates of conversion, low selectivity and reproducibility [26]. As a matter of fact, these problems can be addressed by using flow electrochemistry, usually achieving higher rates of conversion of reagents to products [27]. Moreover, electrochemical flow cells can have a very small gap between

• /trans mixture), the potential of the recycled BMImBF4 to function as a N-heterocyclic carbene precursor was demonstrated. Interestingly, the reaction selectivity is completely lost using the recovered IL, and experiments are undergoing in order to understand the cause of this selectivity loss. Batch vs

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• and successive treatment with 1 M HCl gave 2-cyanonaphthalen-1-ols or 3-(3-cyanoethyl)phthalides. On the other hand, the reaction of 2-acylbenzoates with methyl vinyl ketone under the same conditions produced 3-(3-oxobutyl)phthalides as the sole products. What determines the product selectivity was

• context, we report here that the electroreduction of o-acylbenzoates 1 with acrylonitrile (2a) in the presence of TMSCl and subsequent treatment with 1 M HCl gives 2-cyanonaphthalen-1-ols 3 or 3-(3-cyanoethyl)phthalides 4 (Scheme 3). The product selectivity depends on the position of the methoxy

• 2 and subsequent rearrangement to 3 are also discussed. In particular, the latter mechanism was studied using density functional theory (DFT) calculations and it was suggested that the ΔG for the cyclization step of an intermediate enolate anion determines the product selectivity. Results and

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• methodology is decorated with several advantages like scalability and selectivity. Additionally, no column chromatographic purification was required at any stage and each step was high yielding. After the synthesis of starting materials, the Morita–Baylis–Hillman reaction was explored for C-3

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• HDAC proteins, gives them good biological activity in inhibiting these proteins. To date, three HDAC inhibitor drugs containing this functional group in their structure have been approved [6][7] (Figure 1). However, the main disadvantage of many HDAC inhibitors is their low selectivity: most of them

• increase in the overall yield (from 52 to 71%) and selectivity (from 1.4:1 to 2.5:1) in favor of the O-isomer 24a were observed (compare entries 5 and 6 in Table 1). The best alkylation results were obtained when the alkylation reaction was carried out at 50–60 °C. These reaction conditions proved to be

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• photocyclization reaction sites of 5 were predicted by the orbital-weighted Fukui function in Multiwfn using Gaussian 09 [31][32] at the B3LYP/6-31G** [33] level of theory to verify the reaction-site selectivity of oxidative photocyclization further. Results showed that the conformations of 5a are varied, but the

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• cycloadducts in moderate to good yields with high diastereofacial selectivity. Moreover, several unstable 1,2-disubstituted cyclopropenes were successfully trapped by the stable 1,3-dipole under mild conditions. The mechanism of the cycloaddition reactions of cyclopropenes with PRP has been thoroughly studied

• -substituted cyclopropene 2c [32] with PRP (1) also proceeded with full diastereofacial selectivity, giving the corresponding cycloadduct 3c in acceptable yield (72%). On treatment of cyclopropenes 2d [32], 2e [33] both containing multiple bonds with stable azomethine ylide 1, the 1,3-DC reaction occurred in a

• studied in the reaction with 1 to determine whether these 1,3-DC reactions would similarly proceed with high diastereofacial selectivity. The reaction of 3-methyl-3-phenylcyclopropene (2j) [36] with ylide 1 resulted in the formation of a 1:1 adduct and the cycloaddition with cyclopropene 2j occurred at

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• of hydrogen with a pressure of 1 bar, a good selectivity for the hydrogenation of the external alkene is achieved providing enone 27. The reaction mixture containing enone 27 is then mixed with tosylhydrazone and passed through a column with sulfonic acidic resin Amberlyst-15 to catalyze the

• Lindlar catalyst containing toxic lead salts, selectivity is achieved by the improved reaction control in flow. A solution of alkyne 31 in methanol is mixed with a stream of hydrogen and pumped at room temperature and 2.5 bar through a tubular glass column containing a Dowex-supported palladium catalyst

• . Optimization of process parameters revealed that at a conversion of 75% a good selectivity of 89% for hydrogenation of alkyne 31 to alkene 32 is achieved affording a mixture of (Z)- and (E)-isomers in a ratio of 80:20 [37]. Floral odorants Floral notes, such as rose, jasmine, orange blossom, or lavender, are

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• its synthetic utility were investigated employing various dienes such as furan (18), 1,3-diphenylisobenzofuran (24) (DPIBF) and substituted anthracenes 31, 36 and 39 (Figure 3). Exclusive norbornene exo-π selectivity [24] was observed in all cycloadddition reactions. Selected five-membered dienes were

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• pressure, much higher temperatures around 950 °C are actually required. At these high temperatures, the selectivity of the process is a challenge. Possible side reactions such as hydrogenation of CO and CO2, decomposition of CH4, and the Boudouard reaction lead to the formation of elemental carbon [31

• series of promising systems have been produced for this purpose. These include (Fe2.2C) NPs [39], (ICNPs@Ni; 29 wt % Ni), and (ICNPs@Ru 1 wt % Ru) on a silica-alumina support (SiRAlox). The Ru nanoparticles far outperformed the previously known catalysts. A methane yield of 93% with complete selectivity

• 56% (87 + 88) was obtained for the Diels–Alder cycloaddition, and suppressed polymerization at room temperature. This mixture was then converted in a second step and an Amberlyst 15TM-catalyzed cyclization at 60 °C gave 88 with a selectivity of 95%. Reactions such as polymerizations that inhibit the

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

• alternative to conventional solvent-based protocols, offering unique advantages in terms of sustainability, reaction times, yields, reactant solubility, selectivity, and chemical reactivity. Although ball milling methods are widely used for the synthesis of various classes of compounds [26][27][28][29][30][31

• azobenzenes in MeCN [52], we investigated how substituents of different donor strength affect the selectivity, reactivity, and reaction pathways of halogenation of azobenzene substrates under mechanochemical conditions. Halogenation of azobenzenes with strong electron-donating substituents In contrast to the