Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• his kind contributions for NMR analysis. Funding M.H.Ç. and B.N are grateful to The Scientific and Technological Research Council of Turkey (TUBİTAK) (Project number 2209-A) for financial support. Ziya Dağalan thanks to YÖK 100/2000 and TUBİTAK BİDEB 2211A program for their support.

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• insufficient evidence provided even by meticulous NMR analysis and eventually had to be confirmed by X-ray crystallography (Figure S1, Supporting Information File 1). Changing the ester function from an ethyl to an allyl group enabled a very mild cleavage using a Pd-mediated reaction with triethylsilane [28

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• data for the new compounds. Acknowledgements We acknowledge the Ph.D. student Otto Daolio Köster for the fruitful discussions and assistance with the experimental work, and Mr. Anderson S. Pedrosa for technical assistance with NMR analysis. Funding We thank the financial support of the São Paulo

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

• equiv of NaH in DCM under conditions similar to our previous reports on the deoxygenative trifluoromethylthiolation of carboxylic acids [31]. 19F NMR analysis of the crude reaction mixture after 2 h at rt revealed no conversion towards the desired acyl fluoride product 2a, however, 30% of thioester 3a

•  1, entry 9). To further investigate the potential for reducing the loading of the deoxyfluorinating reagent, 0.5 equiv of the carboxylic acid substrate 1a was reacted with 0.5 equiv of both BT-SCF3 and DIPEA in DCM for 30 min at rt. 19F NMR analysis of the mixture indicated the clean formation of

• product resulting from addition of 1 to thiocarbonyl difluoride. After a further 30 minutes at rt, 19F NMR analysis of the crude mixture indeed indicated the formation of 2a in an overall yield of 74%, implying both pathways are feasible and that sub-stoichiometric amounts of BT-SCF3 relative to the

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• indicated that CavA specifically oxidizes albicanol (5) and drim-8-ene-11-ol (6) to synthesize 7–9, while other substrates showed no reactivity with CavA (Figure 4c). Following this, we increased the substrate concentration to enrich and isolate these products, elucidating their structures through NMR

• analysis (Figure 4b). In these experiments, CavA was found to hydroxylate drim-8-ene-11-ol (6) at the C-3 and C-7 positions to produce 8 and 9, respectively, while albicanol (5) was modified only at the C-3 position. Compound 7 is a known natural product, and its chemical structure was determined by

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• . Purple arrows in (b) indicate the split peaks. The 1H NMR spectrum of purified 5b was measured in D2O with 2% NaOD (Figure S12, Supporting Information File 1). 13C NMR analysis of the same sample was not possible due to the high ionic strength of the solution. NMR characterization was performed using a

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• glutamate decarboxylase, and incubated with BaeJ-KS2. Substrate binding was demonstrated through 13C NMR analysis of the products against the background of various control experiments. Keywords: bacillaene; biosynthesis; enzyme mechanisms; isotopes; trans-AT polyketide synthases; Introduction Polyketides

• have established a new method based on stable isotope (13C) labelling to investigate the KS domain substrate specificity that makes use of simple 13C NMR analysis of protein preparations obtained by a buffer exchange after enzyme incubations with substrate surrogates (SNAC esters), and its application

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

• temperature (rt), the desired unsaturated ε-AA derivative 4a was obtained in 75% isolated yield (Table 1, entry 1). Isolation and NMR analysis demonstrated that this model reaction provided amino acid 4a with good E-selectivity and excellent regioselectivity (E/Z = 91:9, 1,4-/1,2-addition >20:1). Control

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• in 96-well plates (Iwaki) and cultured overnight. Various concentrations of compounds were then added, and cells were incubated for 72 h. Cell proliferation was measured by the MTT assay. Structures of compounds 1, 2, and 5. Planar structure of polycavernoside E (1) based on 2D NMR analysis. Relative

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• ). After large-scale cultivation, 3 was isolated and subjected to nuclear magnetic resonance (NMR) analysis, which suggested that 3 is the C-5′ desmethyl form of preterretonin A [17]. However, several missing signals in the 13C NMR spectrum, likely due to keto–enol tautomerization in the D-ring, hindered

• designated as 5′-demethylinsuetusin A1. Unlike compounds 3–7, the molecular formula of 8 was determined to be C25H38O5, which corresponds to the hydrogenated form of 7. NMR analysis revealed that the double bond at C-2′/C-3′ of 7 was reduced to a single bond in 8 and that 8 contained the enol functionality

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

• reproducible. Unsuccessful substrates for these reactions were also detected (Scheme 4). The use of 2-amino-3-hydroxypyridine provided a complex mixture of products (1H and 13C NMR analysis). When 6-amino-2-thiouracil was used, only the starting materials were recovered. Regarding the aldehyde component, the

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• IMS Q-Tof liquid chromatograph mass spectrometer. For NMR analysis, we utilized an AVANCE II 600 spectrometer, referencing residual solvent peaks at δH/δC 7.27/77.0 ppm in CDCl3 for chemical shift calibration. We utilized commercial silica gel from Yantai Xinnuo New Material Technology Co., Ltd

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

• reaction of compound 1a with Selectfluor in acetonitrile (MeCN) gave high yields of the monofluorinated product 2a with no difluorinated product being observed by 19F NMR analysis of the product mixture after 5 h (Scheme 1). In contrast, attempts to fluorinate 1a with one equivalent of fluorine gas in MeCN

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• monochloride (ICl). We found that olefins 1a and 1b reacts with ICl under the influence of sunlight to form previously unknown 2-chloro-3-iodo-1,1,1,4,4,4-hexafluorobutane (5, Scheme 4). Pure final product 5 was isolated by distillation at 112 °C in 85% yield. NMR analysis as in the case of bromo derivative 2

• distillation in 52% yield for 6a,b and 34% yield for 7a,b. NMR analysis showed the mixtures of (E)- and (Z)-isomers in both cases with the ratio E/Z = ≈4:5 for 6a,b and E/Z = ≈1:2 for 7a,b. The configuration of the isomers was determined by the 5JFFcis coupling constant in the 19F{H} NMR spectrum (ca. 0 Hz for

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• host–guest complex consisting of neutral [10]CPP and [5]CPP, [10]CPP⊃[5]CPP [31]. While the 1H NMR analysis also supported the closed-shell electronic structure of both the host and the guest, neutral [10]CPP and [5]CPP2+, respectively, a partial CT from the host to the guest was suggested by the

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• during purification by silica gel chromatography. On the other hand, NMR analysis of the crude reaction mixtures may be misleading due to possible overlap of the signals of H-3eq belonging both to disaccharide and monosaccharide derivatives sometimes present in such glycosylation mixtures. At low

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• manner, ultimately affording 27 with 90% yield. The formation of intermediates 24, 25, and 26 was elucidated through 1H NMR analysis, of which 24 and 26 were successfully isolated and characterized. A comprehensive analysis of the [2 + 2] CA–RE reaction activation parameters via 1H NMR spectroscopy

• yield for the ring-formation process was modest at 5% (see Scheme 16) [121][122]. The macrocycle in 46 was observed to engage with the peptide segment in low-polarity solvents. In contrast, 1H NMR analysis suggested that the macrocycle disengaged from the peptide segment and relocated along the alkyl

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• result indicated that CmaG is a component of Cma PKS. From NMR analysis and high-resolution (HR)MS analysis ([M + H]+ ion at m/z = 222.0766, which corresponds to C11H12NO4+, calcd. 222.0761) of purified 6, the structure of 6 was determined as N-acetyl-3-aminocoumaric acid (Figures S9–S13 and Table S1 in

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• spectrum) [106], we never detected such a peak in 19F NMR spectra of the neat IL, analysed after reaction work-up, keeping it under vacuum to completely eliminate diethyl ether traces before NMR analysis. It should be mentioned that the solution was kept in the NMR tubes only for the time necessary to

• the 19F NMR analysis of BMIm-BF4 after anodic oxidation in a divided cell, which shows a peak at −147.3 ppm (besides the peak at −150.6 due to BF4−) (see Supporting Information File 1, Figure S1e), which is replaced by a peak at −144.0 ppm (referred to −150.6 ppm for BF4−) when the electrolysis is

• . Therefore, while confirming the presence of the adduct, we could not quantify it. The next choice was DBU (1,8-diazabicyclo[5,4,0]undec-7-ene). The DBU-BF3 adduct is reported to be very stable in water and in air and not subjected to hydrolysis [115]. The DBU solubility in BMIm-BF4 was confirmed by NMR

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• yields (ca. 80%). NMR analysis showed that compounds 4a and 4c required further purification. Thus, they were recrystallized from acetonitrile, which led to a non-negligible loss of materials, thereby leading to final yields in the 50–60% range. Synthesis of MIC·CS2 zwitterions The synthesis of 1,4

• under high vacuum. 1H NMR analysis revealed that a significant amount of starting material was still present in most cases. Moreover, unidentified byproducts were also detected in some instances. Products 6a and 6b could be isolated in pure form and satisfactory yields upon recrystallization from

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• porphyrins were detected in the mass spectra of some of the products. 1H NMR analysis of the synthesized hexaphyrins proved that the spectra were in consistence with [26]hexaphyrin aromaticity [29]. Several other metal triflates such as Zn(OTf)2, Gd(OTf)3, and Yb(OTf)3 were also tested as catalysts in the

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• the R2 group. The stereochemistry of products 10 and 11 was confirmed by X-ray crystal structure and the 1H NMR analysis of both the major and minor diastereomers [69]. The first cycloaddition gives adducts 12 and 12’ as a diastereomeric mixture. At the second cycloaddition, both major and minor

• symmetry. The stereochemistry of the products was confirmed by X-ray crystal structure and NMR analysis. The reaction mechanism shown in Scheme 11 suggests that a semi-stabilized AMY 16 generated from the reaction of glycine and arylaldehydes undergoes a [3 + 2] cycloaddition with 14a via the favorable

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• spiroketals (1 and 2) with a tetrasaccharide moiety. For terpenoid glycosides, the 1H NMR spectrum becomes more complex as the number of sugar residues and their lengths increase, which complicates 2D NMR analysis. In such cases, commonly used TOCSY measurements can be supplemented by H2BC and HSQC-TOCSY

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• -substituted triazole 3’a (entry 1, Table 1), in 21% yield, using NiCl2(PCy3)2 as a catalyst and K3PO4 as a base. A methyl handle on the gem-difluoroalkene 1 was used to aid in 1H NMR analysis. The gem-difluoroalkenes were synthesized in one step using sodium 2-chloro-2,2-difluoroacetate and triphenylphosphine

• chemistry applications. In the reaction with piperidine, we observed unreacted organic azide 2b by TLC and 1H NMR analyses. Based on the 1H NMR analysis, 0.4 equiv of 2b had reacted to form the product, 0.9 equiv of 2b had decomposed to form aniline, and the remaining 0.2 equiv of 2b was unreacted

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• =CHC(=O)Me] with arenes in Brønsted superacid TfOH (triflic acid, CF3SO3H) furnishes 3-methyl-1-trichloromethylindenes (Scheme 1a) [11]. Based on NMR analysis in TfOH and theoretical DFT calculations, it has been found that the reaction proceeds through an intermediate formation of the O-protonated