The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• (1–3 % spectroscopic yield) when BF3·OEt2 was added to the reaction mixture. X-ray crystallography and DFT calculations The solid-state structure of difluoroiodane 6 is shown in Figure 2 and displays the expected square pyramidal geometry around the iodine atom, with only minor distortion (τ5 = 0.191

• Supporting Information File 1). DFT calculations were carried out to gain further insight into the structures of iodine(V) fluorides 21 and 22 whose X-ray structures could not be obtained, and hypothetical iodine(V) amides 7a and 7b which could not be made. Comparisons were made with iodine(V) compounds 6

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• reaction step for the synthesis and purification of the starting azomethines 9, we cannot propose the Ugi-3CR approach as more suitable compared to the Ugi-4CR approach. The structure of the Ugi bisamides 5–8 were proved by X-ray diffraction study on the example of substance 8c (Figure 2), according to

• conventional thermal heating, amide 10a was isolated, albeit in a lower yield and accompanied with tar formation. In addition to the 1H, 13C NMR spectra and mass spectrometry data, the structure of compound 10d was established by X-ray diffraction analysis (Figure 3). It was also found that the substituents at

• case of bisamides 5d, 6a, 6c, 7b, 8a, and 8c (Table 2), additional transformation products were also isolated from the reaction mixture. According to 1H and 13C NMR, MS, and X-ray diffraction studies these were the corresponding ketobisamides 12, which are products of a nucleophilic substitution of the

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• cyclic imides. The solid-state structures of the N-phenyl derivatives, determined by X-ray crystallography, reveal changes in packing preference based on the number of aromatic rings in the core. The optical and electronic properties of the title compounds compare favorably with other previously

• evaporation of CH2Cl2/MeOH solutions and characterized by X-ray crystallography. 7-Ph crystallizes in the Pbcn space group into a solvent superstructure of π-stacked columns of 7-Ph. The imide groups are pointed in alternating directions within a stack. While this may occur in part as a consequence of the

• -Ph as determined by X-ray crystallography. Representative C=O···H–C and C–H···π interactions are indicated in teal and magenta, respectively. Top-down views of π-stacking modes in c) 7-Ph and d, e) 8-Ph. Hydrogen atoms have been removed for clarity in c–e. Atom color code: C = tan, H = white, Cl

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• single diastereomer (Scheme 5, Table 3), while N-phenylglycine afforded the enamine derivative 10 (Scheme 6, Table 4). Both structures were confirmed by single-crystal X-ray diffraction of compounds 9a and 10a (Figure 2). The diastereoselectivity observed in the hemiaminals and their stability can be

• further confirmed by single-crystal X-ray diffraction of compound 12c (Figure 3). Conclusion In this work, we have demonstrated the straightforward access to a variety of complex nitrogen heterocycles by using unprotected deactivated amines tethered to carboxylic acids combined with arylglyoxals in the

• functional group in the resulting Ugi adduct can be exploited in different post-condensation strategies to generate multiple fused nitrogen heterocycles in an easy manner. Fused heterocycles containing the piperazine and diazepine core. X-ray diffraction structures of pyrrolopiperazinones 9a (left) and 10a

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• subsequently overexpressed in insect cells and purified as soluble proteins, culminating in the elucidation of the X-ray crystallographic structure of MaDA (Scheme 5B, PDB: 6JQH). With these key enzymes in hand, Lei and co-workers conducted a chemo-enzymatic total synthesis of 3 and related natural products

• the Diels–Alder reactions (Scheme 6B). Notably, MaDA-3 exhibited high exo-selectivity (original MaDA: endo-selective) and enabled the enantioselective rapid total synthesis of guangsangon J (60) and mongolicin F (61), which are epimers of 58 and 3, respectively. Comparative analysis of the X-ray

• total synthesis of 3 utilizing an identified Diels–Alderase, MaDA. (A) Chemo-enzymatically synthesized natural products by using the originally identified MaDA. (B) MaDA homologue enzyme MaDA-3: X-ray crystal structure and synthesized natural products by leveraging this enzyme. Proposed biosynthetic

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• revealed by X-ray diffraction analysis. Upon visible-light irradiation, significant transformations of the DA geometry enabled transformations of the supramolecular assemblies on a microscopic scale, subsequently disassembling macroscopic soft scaffolds of DAs. The current work shows promising use for the

• investigated with through-view wide-angle X-ray diffraction (WAXD). The 2D WAXD image of the macroscopic soft scaffold of DA11 showed a diffraction ring in the region of q = 0.5–5.0 nm−1 (Figure 4c), which was similar to that of DA10 [37]. A low degree of angular dependency was observed in the macroscopic soft

• Rigaku NANOPIX equipped with a HyPix-6000 (Rigaku) detector. The scattering vector (q = 4⋅π⋅sin(θ)/λ), scattering angle θ, and the position of the incident X-ray beam on the detectors were calibrated using several orders of layer reflections from silver behenate (d = 58.380 Å), where λ refers to the

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• center. Under the disclosed optimized conditions, the product ent-3ba was isolated as white solid with 85% ee and the enantiopurity of the product could be enriched to 98% ee by single recrystallization. The absolute stereochemistry was determined to be “R” on the basis of single-crystal X-ray

• temperature. The crude reaction mixture was purified by silica gel (230–400 mesh) column chromatography (petroleum ether/EtOAc as the eluent) to give the product 3 or ent-3. Selected examples of drugs and bioactive molecules bearing a pyrazole core. Single crystal X-ray structure of ent-3ba (CCDC 2234286

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• residual water during column chromatography. Unfortunately, attempts to assign the absolute configuration of products 5 failed, as we have not been able to obtain any crystals suited for single crystal X-ray diffraction analysis. Finally, we also tested the suitability of products 5 to access acyclic α-AA

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• produced in the reaction, while the other diastereomers were not detected. In order to elucidate the relative configuration of the obtained compounds, the molecular structure of the compound 4a was determined by single crystal X-ray diffraction (Figure 1). From Figure 1, it can be seen that the fused

• can be performed with a wide variety of substrates. The molecular structure of the compound 6g was determined by single crystal X-ray diffraction method (Figure 2). The o-methoxyphenyl group exists on the trans-position of the fused pyrrolidine unit. The methoxycarbonyl group also exists on the cis

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• suitable for single-crystal X-ray diffraction could be obtained and confirmed the product structure with the presumed regioisomer (Scheme 3). A library of over 50 triazole products 21aa–vg was successfully synthesized with yields ranging from 28% to quantitative, combining four different pyrazole-carbon

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• types of aforementioned structures were proved by X-ray analysis. Keywords: allomaltol; Boulton–Katritzky rearrangement; hydrazones; pyrano[2,3-d]isoxazolones; recyclization; 1,2,3-triazoles; Introduction The Boulton–Katritzky rearrangement (BKR) also known as mononuclear heterocyclic rearrangement is

• spectroscopy and high-resolution mass spectrometry. Moreover, X-ray analysis was used for confirmation of structure of compound 4g (Figure 1). A plausible mechanism of the studied rearrangement is presented in Scheme 5. At first, anion A is generated from starting hydrazone 3 under action of base. Next

• obtained the recyclized product 6a (Scheme 6), whose structure was confirmed by 1H, 13C NMR spectroscopy, high-resolution mass spectrometry and X-ray analysis. Based on the aforementioned reaction we have synthesized a set of pyrazolylisoxazoles 6 (Scheme 7). The proposed mechanism of investigated

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• [22]. An X-ray structure of 9 allowed us to solve its absolute configuration and measure the C2–C7 distance to be 3.31 Å. This distance matches reasonably well with the calculated distance, 3.36 Å, of the lowest energy conformer of 9. Calculation of the proposed 6,7-epoxy derivative of 2, which was

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• in a much shorter time (Table 1, entry 4) when the temperature of the reaction medium was increased to 50 °C. According to X-ray and Raman spectroscopy techniques, triglyceride molecules in liquid form are arranged in a dynamic chain-like conformation [114][115][116]. As the temperature of the

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• -withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• group, could not be isolated at all, since the reaction resulted in an inseparable mixture of several products. The structure of 6b could be independently confirmed by X-ray crystallography (Figure 2). Both phenyl rings are found to be twisted in an angle of approximately 45° from the quinoline core. As

• the 6-position in comparison to the 8-position. The structure of product 9f was confirmed by X-ray crystallography (Figure 3). The thiophene ring in 4-position is in plane with the quinoline core, while the other ring is twisted in an angle of approximately 85°. This might be explained by an

• dehalogenation at position 3. In particular, the side-product 6b was isolated in 25% yield during the purification of 12b. The structure of product 12d was proven by X-ray crystallography (Figure 4). All three phenyl rings are found to be nearly in plane with the quinoline core, showing only a slight twist of 5

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• , and methyl anthranilate, with selenium dioxide in acetonitrile. A systematic analysis of the reaction products with the help of 77Se NMR and single-crystal X-ray crystallography revealed that the reaction progress follows three major reaction pathways, electrophilic selenation, oxidative

• electrons over the adjacent carboxylate function, which prompted the selenation pathway, leading to the formation of two of the isomeric diorganyl selenides of methyl anthranilate. The diaryl selenides were structurally characterized using single-crystal X-ray diffraction. Density functional theory

• with arylamines follows a complex reaction pathway, leading to a mixture of compounds. We established the possible reaction pathways using 77Se NMR spectroscopy and single-crystal X-ray crystallographic studies. Density functional theory (DFT) calculations were carried out to understand the relative

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• achieved with one-pot Suzuki–Miyaura coupling to arrange phenylene rings and pyridinylene rings in an alternating fashion. Analyses with UV–vis spectroscopy showed changes in the photophysical properties with nitrogen doping, and X-ray crystallographic analyses experimentally revealed the presence of

• biased charges on the peripheral nitrogen atoms. Keywords: cross coupling; macrocycles; nitrogen doping; UV–vis spectroscopy; X-ray charge density analysis; Introduction Graphitic carbonaceous sheets of graphene continue to attract considerable attention, which lead us to explore structural defects

• nitrogen-doped [n]CMPs (3) containing outward-radiating nitrogen dopants. The properties and structures were investigated with UV–vis spectroscopy and X-ray crystallography, which revealed the fundamental properties of the nitrogen dopants in the macrocyclic structures. Results and Discussion Nitrogen

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• 305-8577, Japan 10.3762/bjoc.20.100 Abstract The addition reaction of C60 with silylene 1, a silicon analog of carbene, yielded the corresponding bis-adduct 3. The structure of 3 was determined by single-crystal X-ray structure analysis, representing the first example of a crystal structure of a

• -silylene adduct 3 of C60 based on spectroscopic measurements, X-ray crystallography, electrochemical analyses, and theoretical calculations. Results and Discussion Synthesis of bis-silylene adduct 3 The synthesis of the silylene adduct was conducted using a modified literature procedure [15]. A degassed

• ions of 3. Finally, the structure of 3 was established by single-crystal X-ray structure analysis. The ORTEP diagram of 3 is presented in Figure 5 with the selected bond lengths and angles collected in Table 1. The cage C–C bond lengths of the addition sites are C1–C9: 1.623(2) Å and C21–C40: 1.6282(19

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• products (Scheme 5). Interestingly, the dearomatized intermediate resulting from the reaction of base and Mn3 was isolated and characterized by X-ray analysis during the mechanistic investigation. In 2018, Kempe et al. disclosed that the choice of the base plays a critical role in the BH method for the

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• inhibitor of homeodomain-interacting protein kinases (HIPKs) [32], and combretastatin A-4 analogs evaluated for their anticancer properties against a panel of 60 human cancer cell lines [33] (Figure 2). The structures of all new compounds were confirmed by 1H and 13C NMR and HRMS. X-ray diffraction studies

• -oriented heterocyclic systems. Some examples of biologically active isoxazolo[4,5-b]pyridines with antibacterial [8], anticancer [12] and cytotoxic [10][13] acitivities. Biologically active analogs of compounds 13. X-ray crystal structures of compounds 12c (top left; the second crystallographically unique

• . Yields of compounds 12 and 13. Supporting Information Supporting Information File 16: Experimental section, NMR spectra and X-ray analysis data.

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• ). Single crystal X-ray diffraction data could be obtained for three DPQDs. One reveals pairwise hydrogen bonding in the solid state as well as a herringbone packing arrangement rendering it a promising candidate for additional studies in the context of organic optoelectronic devices. Keywords: conjugated

• moderate to excellent hole transport mobilities (1.5 × 10−3 and 1.5 cm2/Vs, respectively) [21]. In 2012, Miao et al. reported an H-bonding capable 1,4-dihydropyrazinopyrazine fragment within N-heteroacenes [22]. The X-ray analysis of single crystals revealed the formation of highly-ordered ribbons

• exhibits a noteworthy impact on the thermal stabilities (analyzed by TGA) of the compounds. The single-crystal X-ray diffraction of DPQD 2b exhibits a desirable herringbone solid-state arrangement for a potential OFET application. Complementary gas-phase computational analysis has provided insight into the

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

• : Experimental procedures, spectra and X-ray data. Acknowledgements We thank Lucie Bednárová from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences for the help with the analysis of compound 13. Funding The work was supported by the National Institute of Virology and

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• (SQUID) [21][22] and X-ray magnetic circular dichroism (XMCD) spectroscopy [23]. However, only a tiny paramagnetic behavior of encapsulated ferrocene was observed, and no magnetic host–guest interactions were reported due to the diamagnetic nature of CNTs. Activated carbon fibers (ACFs) consist of a

• magnetic interactions between the nanographene host and FeCp2 guest molecules to achieve a ferromagnet using nanographene host–guest systems. In this study, we introduced ferrocene to ACFs and investigated the magnetic interaction between the host ACFs and ferrocene as magnetic guest molecule using X-ray

• surface of ACFs, which were removed by heating the FeCp2-treated ACFs at 150 °C for 3 hours without FeCp2 vapor. XPS spectra were recorded using a PHI-5600 (ULVAC-PHI) with an Al Kα X-ray source (1486.7 eV) for samples mounted on an indium film. Raman spectroscopy measurements were performed by LabRAM HR

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• complement the growing glycan content of the PDB. Keywords: carbohydrates; database; N-glycans; N-glycosylation; polysaccharides; validation; website; Introduction Carbohydrate modelling is an important but often cumbersome stage in the macromolecular X-ray structure solution workflow. The accurate