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

• aromatic Grignard reagents which do not bear ω-magnesium alkoxide functionalities: in that case, EtOMgX can be used as an external additive to enhance the cross-coupling selectivity, in line with the alkyl–alkenyl and aryl–alkenyl cross-coupling methods discussed earlier (Scheme 5) [32]. The beneficial

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• [14], we had undertaken some preliminary investigations into the use of commercially available Diversinate™ reagents and showed the bicyclic nitrogen-rich core of Series 4 was amenable to this chemistry, with radical sulfinate substitution occurring with high-selectivity at C-8 and in respectable

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• isolated in 34% yield indicating that steric effects play a role during the oxidation step. We further wanted to investigate different arenes, but due to the lack of selectivity of the primary benzyl acetates in the Friedel–Crafts step, we were limited to para-substituted arenes, which unfortunately all

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• platforms [66], the group considered a system in which a photoexcited catalyst oxidatively cleaves a siloxycyclopropane with endo selectivity [67], leading to aryl–nickel capture and reductive elimination. Thus, when substrates 121 and 122 were photoirradiated with blue LED light at 45 °C in the presence of

• drastically the radical stability, nucleophilicity, and selectivity of 139 [73]. Furnishing of the common scaffold 130 can be carried out via an attack of intermediates of this type (e.g., 139) on Michael acceptors. Tosyl group deprotection of 130, followed by selenium anhydride oxidation and catalytic

• process, two major families of natural compounds are formed, namely the aporphine and the morphinandienone alkaloids. Mimicking the selectivity of the natural process in laboratory setups commonly proves tricky, producing an irreproducible yield of isomers for both classes. Recently, Felpin’s group

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• IC50 0.96 µM) and 4.85 µM (amphotericin B IC50 4.87 µM), respectively. Furthermore, digyalipopeptide A (1) produced IC50 values of 10.07 µM (ampicillin IC50 0.18 µM) and 10.01 µM (ampicillin IC50 1.53 µM) for Staphylococcus aureus and Shigella sonnei, respectively. The selectivity and toxicity profile

• of compound 1 was investigated using normal cell lines, macrophages RAW 264.7. When tested against normal macrophages, compound 1 gave an IC50 value of 71.32 μM. Selectivity indices (SI) were obtained by calculating the ratio of the IC50 in RAW 264.7 to the IC50 in the respective microbe and

• 10.01, 18.71, and 10.01 µM, respectively. The laboratory standard itself produced IC50 of 1.53 µM for Shigella sonnei, Shigella flexneri 1.76 µM, and Staphylococcus aureus 0.18 µM, respectively (Table 3). The selectivity and toxicity profile of compound 1 was also investigated using normal cell lines

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• selectivity was achieved by chelation of the Sm(III) intermediate with hydroxy groups present on the structure. As the direct coupling with the A-ring precursor failed, a strategy to build this part was developed, starting with a sequence involving a protection of the alcohols as MOM ethers, lactone

• suitable starting material for the SmI2-promoted pinacol coupling, directed by the free hydroxy group, affording a complete selectivity in the formation of the 7-membered ring B. The synthesis of grayanotoxin III was then achieved by acetylation of the secondary alcohols, oxidative cleavage of the MOM

• , obtaining excellent selectivity in all cases. Alternatively, the same year, the authors published a vinyl radical cyclization occurring in presence of n-Bu3SnH, providing a stereoselective access to the bicyclo[3.2.1]octane unit corresponding to the CD rings [25]. Newhouse’s synthesis of principinol D In

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• oxidative coupling processes (also known as cross-dehydrogenative coupling), as well as late-stage CH-functionalization. Oxidation processes are recognized as a challenge in fine organic synthesis technology [10][11] due to selectivity problems and frequent need for toxic transition metal salts and

• stoichiometric oxidants. The development of organic chemistry is strongly affected by rising “green” demands to synthetic methodologies, including reduction of waste formation, low trace-metal content in drug compounds, high energy-efficiency and selectivity of processes. In the last decade researchers proposed

• that hydrogen bonding is considered as one of the key factors determining the selectivity of catalyst-free sulfoxidations [68]. In such reactions, the selectivity of sulfide oxidation by oxone (sulfoxide/sulfone ratio) was controlled by the solvent nature (deeper oxidation was observed in water than in

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• secondary metabolite biosynthetic enzymes are distant paralogs of enzymes involved in primary metabolism [63][71]. These NP biosynthetic enzymes are hypothesized to have undergone significant sequence and selectivity changes while still operating based on the same reaction mechanism (e.g., fatty acid

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• alcohol. We build on a commercially available imidazopyridine derivative and conceived a protecting group strategy to enhance solubility and selectivity to orchestrate the installation of the exocyclic amino and hydroxy groups. Results and Discussion 1-Deazaguanine Previously described syntheses for 1

• -1-deazapurine [16], the key reactions are copper-catalyzed benzyl ether formation and site-specific nitration. The application of protecting groups was necessary for reasons of solubility and to improve selectivity. The obtained heterocycles may serve as core compound for further structural

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ring smoothly, leading to the exclusive formation of biaryl intermediate 11 in a yield of 82%. It is worth noting that the methoxy substitution in the substrate played a crucial role in controlling the selectivity of the cycloisomerization according to our previous study [15]. It was rationalized that

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