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

• ] as catalyst to achieve an NH-indole–C–H carbonylation [57]. A base was added to improve the efficiency of the process and an oxidant to restore the catalytic active species. The reaction was carried out under a low pressure of CO (1 bar) at 110 °C in xylene for 24 hours (Scheme 26). In 2018, the Zhou

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• of the de novo approach and furthermore provides an extra efficiency, complexity and diversity in the same number of steps (Figure S1, Supporting Information File 1). Also, it offers a flexibility of placement of the tetrazole moiety in the scaffold and enables additional facile post-modifications

• -effective and readily available materials not only simplifies the process but also opens up avenues for gram-scale production. This method stands out for its efficiency, simplicity, and environmental friendliness, in contrast to previous syntheses. The incorporation of these tetrazole building blocks into

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• 2.0 equiv of diisopropylethylamine (DIPEA), 2a could be obtained in quantitative 19F NMR yield although a reduction to 1.5 equiv led to a significant drop in efficiency, delivering the acyl fluoride in only 30% 19F NMR yield together with 45% of thioester 3a (Table 1, entries 4 and 5). At this stage

• fluoride product (Table 1, entry 9). Although representing a considerable drop in efficiency compared to using 1.25 equiv of BT-SCF3, this observation provides an interesting insight into the reaction mechanism (vide infra). Changing the solvent from DCM to THF or MeCN resulted in no significant change in

• the efficiency of the reaction, whereas a 19F NMR yield of only 11% was achieved in DMF (Table 1, entries 10–12). Increasing the reaction concentration to 0.2 M in DCM led to a reduction in the 19F NMR yield of 2a to 74% (Table 1, entry 13). Finally, optimisation of the reaction time revealed the

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• . Keywords: annulation; arylocyclization; 3,4-benzocoumarin; diaryliodonium salts; naphthol; Introduction Diaryliodonium salts as electrophilic reagents have attracted significant attention in the field of organic synthesis owing to their efficiency and selectivity [1][2][3][4][5][6][7]. Particularly, they

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• 1990s when Kropp's pivotal paper on the surface-mediated hydrochlorination of unactivated alkenes reignited interest [10]. Since then, continuous efforts have been made to enhance the generality, efficiency, and functional group tolerance of hydrochlorination reactions. Recently, several groups reported

• thermally treated alumina and SOCl2 (2 equiv) as an ideal HCl precursor, affording the product 62 in a 94% yield with 100% conversion in only 18 minutes of reaction time (Table 4, entry 3). During their investigations, they discovered a correlation between the efficiency of the hydrochlorination reaction

• functional group tolerance. Yang reported a hydrochlorination promoted by visible light over platinum, gold, and palladium supported on zirconia [74]. The reaction demonstrated moderate efficiency, yielding an 85:15 mixture of products 100 and 126 with low conversion (Scheme 20). The use of hydrochloric acid

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• [8]. Further improvement of the PDT method requires the search for new photosensitizers having higher photoactivity, tumor selectivity, and high singlet oxygen quantum yield, as well as low in vivo toxicity [7]. Therefore, some strategies have been developed to enhance the therapeutic efficiency of

• )sensitizers that are efficient for both PDT and boron neutron capture therapy (BNCT) [27][39]. The preparation of compounds with dual therapeutic efficiency is of great importance since they improve the therapeutic effect of sensitizer by the action on the different cellular sites. Here, we report the

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• exhibiting high activation efficiency. The metabolites produced by the activation of silent genes are expected to be physiologically significant. In the case of high-temperature culture or co-culture methods, these compounds may play roles in thermotolerance or communication between different species

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• CsCCD2 that exhibits broader substrate specificity and higher catalytic efficiency through computational modeling. Heterologous expression of the S323A mutant of CsCCD2 in yeast led to a 4-fold enhancement in the production of 1, with a crocetin (1) titer of 107 mg/L in a 5-liter fed-batch fermentation

• duplication events during genome evolution [96]. When expressed in the callus of Nicotiana tabacum, GjCCD4a exhibited a higher efficiency in carotenoid cleavage than CsCCD4a [85]. ALDHs: ALDH utilizes NAD+ or NADP+ as cofactor to catalyze the oxidation of acetaldehyde into carboxylic acids. In 2018, Demurtas

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• efficiency of synthetic approaches, have already shown a growing influence in the synthesis of bioactive natural products, pharmaceutical components, and other valuable molecules with the development of microbial genetics and enzyme engineering [19][20][21][22]. The comprehensive investigation of TE domains

• -acetylcysteamine. Via bioinformatics analysis, Parkinson and co-workers most recently reported the characterization of Ulm16, the PBP-TE predicted to cyclize ulleungymycin. Compared with previously studied PBP-TEs, Ulm16 showed much higher efficiency and broader substrate scope, producing a variety of ullemgymycin

• functional group changes of its natural substrates. To increase the efficiency of pikromycins preparation, the Sherman lab developed a chemoenzymatic synthesis method through sequential propionate extension and marcocyclization catalyzed by fused PikAIII-TE and PikAIII-PikAIV modules. Based on this study

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• , reaction 2). Two classes of reagents are commonly used: ethynylbenziodoxolones (EBXs) [32][33] and alkynylsulfones [34]. A potential limitation of this method lies in the substitution of the transferred alkyne. The efficiency of the radical addition to those reagents is known to be highly dependent on the

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

• enhanced economic efficiency, eco-friendly practices, and reduced waste. Catalysts with the highest enantioselectivity have been employed in the synthesis of essential chiral intermediates for drug production, such as amprenavir [12], rivaroxaban [13][14], linezolid [13] and salmeterol [7]. Therefore

• with reduced efficiency in the absence of a second stereogenic centre at position 5. Nonetheless, IV proved to be an effective enantioselective organocatalyst in the asymmetric aldol reaction, matching the enantioselectivity levels of other proline-heterocycle derivatives [25]. Overall, our findings

Organic electron transport materials

• Joseph Cameron and
• Peter J. Skabara

Beilstein J. Org. Chem. 2024, 20, 672–674, doi:10.3762/bjoc.20.60

• soluble in ethyl acetate, a green solvent, and solution-processed for PM6:Y6 bulk-heterojunction solar cells with power conversion efficiency > 13% [6]. In addition to orthogonal processing, it has been shown that treatment with base [7] or photo-crosslinking [8] can insolubilise solution-processed layers

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

• . Multicomponent reactions (MCRs) by virtue of high efficiency for the construction of complex chemicals, have shown the superiority in high step and atom economy in organic synthesis [25][26][27]. Over the past two decades, our group and others have developed a transition-metal-catalyzed MCR strategy involving

• 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

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• green catalyst with greater chemical and thermal stability in comparison to other heteropolyacids [43]. HPW has been shown to catalyze MCRs in the synthesis of heterocyclic compounds with high efficiency and chemoselectivity (Figure 2), including functionalized benzo[c]chromeno[2,3-a]phenazine [44

• 1, aromatic/heteroaromatic aldehydes 2, and isocyanides 3 to obtain the imidazo[1,2-a]pyridine derivatives 4 (Scheme 2). In general, the efficiency of the HPW-catalyzed GBB reaction is very dependent upon the type of 2-aminopyridine or isocyanide compound used, and not influenced by different

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• is relatively high. However, this is similar to other myo-inositol dehydrogenases whose KM values are also in the mM range [12][16]. Hyg17 showed a higher catalytic efficiency of 366.7 ± 46.96 M−1 s−1 with myo-inositol as compared to the 29.6 ± 5.28 M−1 s−1 for scyllo-inositol. This reduced catalytic

• efficiency can be attributed to the reduced kcat and increased KM for scyllo-inositol over myo-inositol. We also found that the catalytic efficiency for NAD+ was 452.4 ± 54.49 M−1 s−1 (Table 1 and Figure 2f). Sequence similarity network We generated a sequence similarity network (SSN) for the protein family

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• herbicides remain the most effective solution for weed control due to the associated efficiency and simplicity, they face multiple challenges, such as the emergence and growth of resistant weed populations. It is therefore essential that crop protection research acts rapidly to provide farmers with new

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

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• 13C{1H} NMR spectra contained signals supporting the presence of ketone (e.g., δC = 185.6 ppm for 5a) and ester (δC = 161.9 ppm for 5a) functionalities. Difluoroketoester products were found to hydrate readily to give gem-diol derivatives during aqueous work-up [39], thus reducing the efficiency of

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• associated with low catalyst loading, extremely high efficiency and broad substrate scope and the possibility of use of both organic solvents or water, with the drawback however, of the employment of conventional heating [92]. In 2019, Toy et al. proposed an alternative approach for the Friedel–Crafts

• efficiency would not diminish even after 3 cycles [99]. Several substituted indoles, aldehydes and ketones reacted in good yields (74–98%), with ketones requiring longer reaction rates of 3 hours, due to their lower reactivity. The electron-donating or withdrawing effects of the substituents of the benzene

• yields of 85% after 20 minutes of stirring. The nano-TiO2 catalyst was easily recovered by centrifugation, where it could be reused up to four times, without any reductions in product conversion. What holds back the efficiency of this nanocatalytic protocol is the application of conventional heating, as

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

• chemistry is well documented [1][2]. Traditional approaches for radical generation relied on hazardous reagents and harsh conditions, resulting in low reaction efficiency and undesired byproduct formation [3][4][5][6]. As a consequence, the utility of radicals in organic synthesis remained limited for many

• resulting concentration of radicals. In such instances, opting for a stronger catalytic reductant or utilizing a stoichiometric electron donor can greatly improve the efficiency of radical generation. On the other hand, additional factors such as the ability of Brønsted and Lewis acid additives to promote

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• ). This has prompted an ever-increasing number of research groups to design new synthetic routes towards π-CPCs, aiming at i) new organic structures for improved performances, ii) higher synthetic efficiency and modularity, and iii) better processability of target compounds to build opto-electronic

• same protocol with a photoconversion of 4a thin-film instead of thermal conversion, a decrease of the charge transport efficiency was observed, with electron mobilities of 8.4 × 10−2 cm2 V−1 s−1, which can be ascribed to the lower quality of the PBI thin-film generated upon photoextrusion due to the

• of devices and in situ generation of the active material by late stage S-extrusion. Nevertheless, the synthetic route towards dinaphthothiepine bisimides initially reported suffered from several drawbacks: it had limited efficiency (1.2% overall yield over 8 steps for the synthesis of thiepine 3a

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• exclusively obtained, implying that the expected HAT at the 1’-C position to afford 2 (Table 1, entry 1) had not occurred. In contrast, the reaction efficiency was significantly decreased in the absence of the phosphate base (Table 1, entry 2), and electricity is necessary to proceed the reaction (Table 1

• amidyl radical generation through the PCET mechanism. The above studies provided us with valuable insights into the intriguing electrochemical behavior of 1 (Figure 3). Hydrogen bond formation between 1 and the phosphate base yielded small aggregates, the interaction efficiency of which with the

• was 0.01 M. A glassy carbon anode (φ 3 mm) and Pt cathode (φ 3 mm) were used. Scan rate = 100 mV/s. Plausible models illustrating the size effect of the hydrogen bond complex on the interaction efficiency with electrode surfaces. Plausible mechanism for the inter-/intramolecular hydroamination of 1

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• the resulting products (3ah–aj) can also be obtained with high efficiency. This underscores the viability of integrating this metal-free thioetherification method with other traditional cross-coupling reactions. Sterically hindered ortho-disubstituted thiophenol 2k is also compatible with this

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

• atom efficiency, step and pot economies, decreased number of purification steps, or protecting-group-free synthesis. Multi-step domino [1][2] and one-pot [3] reactions represent a new powerful toolbox in organic synthesis to install molecular complexity economically and sustainably, starting from

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• (2p). However, when using 3,3-difluoro-2-(naphthalen-2-ylethynyl)-3H-indole or 3,3-difluoro-2-phenyl-3H-indole as the substrate, the generated indoles underwent fast HF elimination/aromatization and finally gave indole derivatives (2q and 2r) in almost quantitative yields. To examine the efficiency