Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• acryloyloxazolidinone 183, the reaction gave the expected aldol product 184 in good yields and diastereomeric ratios with a preference toward the syn-adduct (Scheme 47A). Interestingly, when they used methacryloyloxazolidinone 185 as a Michael acceptor, the X-ray analysis of the product showed a rearranged structure

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• configuration of each enantiomer was determined by single-crystal X-ray analysis. In addition, a one-pot synthesis of (±)-incarviditone has been achieved from rac-rengyolone by using KHMDS as a base. We have also assessed the anticancer activity of all the synthesized compounds in breast cancer cells

• structure of rac-incarvilleatone (1) was determined by spectroscopic methods and single crystal X-ray analysis. However, they were unable to obtain single crystals of either of the enantiomers (−)-incarvilleatone [(−)-1] and (+)-incarvilleatone [(+)-1]. (±)-Incarviditone (2), a novel benzofuranone dimer was

• 331.1150 corresponding to the C16H20O6Na [M + Na]+ ion. After some efforts, to our delight, we could obtain single crystals of (±)-4 using EtOAc as a solvent. Finally, the formation of heterodimerized dihydroxy RC product (±)-4 was confirmed by single-crystal X-ray analysis [16]. It is pertinent to mention

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• correlations and today preferentially done by NMR spectroscopy or X-ray analysis, is clearly evident from the fact that wrongly reported structures or structures assigned without any comprehensible basis lead to error propagations and highly confusing situations in the literature. Today many reports are only

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• -Nazarov cyclization of the allyl-substituted imine substrate afforded α-methylene-γ-lactam product 19m in 56% yield. In our previous study, the relative stereochemistry of a tricyclic aza-Nazarov product obtained from a 3,4-dihydroisoquinoline derivative was secured by single-crystal X-ray analysis [35

• X-ray analysis revealed that the relative stereochemistry of lactam 19l with the isobutyl and phenyl groups in a trans arrangement (Figure 1, CCDC 2116978). This finding confirms that both cyclic and acyclic imines undergo the aza-Nazarov cyclization developed in this work via the same

• -lactam heterocycles 19 in up to 76% yield and with good to high diastereoselectivities (4.3:1 to 16:1). We have demonstrated the scalability of the reaction with a gram-scale example. The relative stereochemistry of the α-methylene-γ-lactam products 19 has been determined via the single-crystal X-ray

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• (Figure S23 in Supporting Information File 1) indicating that the single crystal specimens selected for X-ray analysis are representative of their corresponding bulk materials. The crystallographic data for these complexes are summarised in Table 2. The hydrated CD inclusion complexes of 17β-estradiol and

• are isostructural, all of the salient structural features illustrated above and below for the γ-CD·PRO crystal are common to the γ-CD·BES crystal, which was not amenable to single crystal X-ray analysis. Solubility analysis Solubility determinations for the four native CD inclusion complexes (β-CD·BES

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• reaction conditions were not further optimized (Scheme 1). The structure of tetracyclic product 5a was unequivocally confirmed by 1H and 13C NMR as well as single-crystal X-ray analysis. Compound 5a is representative of the hitherto undescribed bistriazole benzodiazepine scaffold. However, 5,6,7,8

• intermediate before the click reaction was established by 1H NMR analysis of the reaction mixture). However, the product of this two-step, one-pot reaction (19) was isolated in respectable 61% yield. The structure of compound 19 was confirmed by the single-crystal X-ray analysis which demonstrated that the

• although the yield of product 21 was diminished compared to that of unsubstituted compound 5a. The structure of compound 21 was also confirmed by the single-crystal X-ray analysis (Scheme 3). All compounds were tested against lung cancer cell lines A549 and NCI-H460 and did not show any appreciable effect

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• crystal X-ray analysis (CCDC 2201614). As evinced by the NMR data, only one diastereomer of product 3aa was obtained. Contrary to the isoxazole-annulated products of a [3 + 2] cycloaddition of nitrones to FPDs [35], product 3aa appears to be stable on storage in solution, which was confirmed by the fact

• close to that of the products obtained from FPDs annulated with a benzoxazine fragment. The structures of products 3aa, 3ab, and 3ha were approved by single crystal X-ray analysis (CCDC 2201614, CCDC 2201616, CCDC 2201615). We also decided to study the effect the benzo-annulated moiety in FPDs has on

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• optimized ttg conformer (left) and for two neighboring molecules (right) from X-ray analysis data. Molecular structures in the solid state of a) (FcS)3P, b) (FcS)3PO [19], and c) (FcS)3PS [7] as established by single crystal X-ray diffraction analyses. C atoms – grey, Fe atoms – brown, O atoms – red, P

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• by X-ray analysis (vide infra). Unlike 3O-TAAD derivatives 2 [21], the obtained 3N-TAADs, 2N,1O-TAADs, and 1N,2O-TAADs are thermally stable and do not suffer from retro-[2 + 2 + 2]-cyclotrimerization to the open-chain tris-imines upon heating. Thus, the presence of at least one N-amido group

• the formation of host–guest complexes Several of the obtained TAAD derivatives were characterized by X-ray analysis (namely, 4a, 4a·HCl, 4b [35], 4c·HCl, Bn-4c, 8a, 19e·3HCl, 21 and 21·HCl, see Figure 2 and Supporting Information File 2). The geometrical parameters of the 1,4,6,10-tetraazaadamantane

• corresponding TAADs 4a,c–e in good to high isolated yields. Trishydrazone 3b with X = NHCO2Et was somewhat less reactive, and its conversion to heteroadamantane 4b required more harsh conditions (reflux in water). TAADs 4a and 4c were converted into their corresponding hydrochlorides, which were used for X-ray

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• care, because TDD easily undergoes racemisation under basic conditions. The X-ray analysis showed an interesting dimer interaction of the enantiomers in racemic TDD through hydrogen bridges, that may support its much easier crystallisation in comparison to enantiomerically pure or enriched TDD. In fact

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• of compound 9a, by single-crystal X-ray analysis. A curious and somewhat unexpected result was obtained when trying to employ N-formyl-N-methylaniline as an arene in the TfOH-promoted arylation of 10a. Instead of the anticipated product 9aa, 73% yield of predominantly trans-configured formate ester

• 16 was obtained and its structure was confirmed by single-crystal X-ray analysis. Presumably, the formation of ester 16 can be justified by the trapping of the carbocation intermediate 17 (vide infra) by the formamide carbonyl oxygen atom followed by hydrolysis of the iminium moiety (Scheme 4

• characterized). cCompound 14 was identified as the reaction product. Preparation of 4-diazo-3(2H)-isoquinolones 10. aConfirmed by single-crystal X-ray crystallography (see Supporting Information File 1). TfOH-promoted arylation of diazo substrates 10. aStructure confirmed by single-crystal X-ray analysis

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• the three components (Se powder, 1a, and 3a) in the presence of Na2CO3 at 130 °C, but unfortunately it did not proceed and gave a complex mixture (Table 1, entry 13). Single crystals suitable for X-ray analysis of 4aa were obtained by repeated recrystallization from dichloromethane/hexane as solvent

• single product, and the regiochemistry of 5-selanyltriazole 8 was confirmed by single crystal X-ray analysis (see Supporting Information File 3). The reaction performed using 10 mol % of CuI and PMDETA as catalytic system afforded only a small amount of product 8 (12%). Based on the results obtained in

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

• -hindered face of TPC (2a) is more favorable than the opposite diastereoisomer 3a' (Scheme 2). Subsequently, our hypothesis about the relative configuration of 3a was confirmed by X-ray analysis that was carried out for the related compound 3e (vide infra). Subsequently, our efforts focused on the

• underwent the cycloaddition reaction to azomethine ylide 1 to form bis-spiro 3-azabicyclo[3.1.0]hexane 3b in 78% yield (Scheme 3). Remarkably, the structure of cycloadduct 3b was additionally verified by X-ray analysis (see Supporting Information File 1, Figure S26 and Table S1). The reaction of 3-ethyl

• during protonation of Ruhemann's purple. Although there was conclusive evidence of the structure of PRP (1) in the Grigg's study (proven by X-ray analysis) [27], we aimed to establish a stability order of tautomers on the basis of calculated relative values of the Gibbs free energy. Upon treatment of

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

• % yields, respectively, as confirmed by NMR spectroscopy (Figures S82–S91 in Supporting Information File 1). Additional support for the formation of succinimide products was provided by the molecular structure of L4-III, resolved by single-crystal X-ray analysis (Figure 3 and Figure S33 and Table S1 in

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

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

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• corresponding quinoxalines 15a–l in good yields (Scheme 5). The structure of 15a was confirmed by single-crystal X-ray diffraction (Figure 2) as a representative example. It should be noted that X-ray analysis of the final quinoxaline unambiguously proves the conversion of the allomaltol fragment into the

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• , the formation of the spirocyclic benzoxepine was not observed. Instead, the principal product of the reaction was compound 2 (as unequivocally confirmed by the single-crystal X-ray analysis of a representative, compound 2a, see Supporting Information File 1), presumably resulting from the dimerization

• of DAS 1a in dichloromethane in the presence of Rh2(esp)2 (0.1 mol %) led to the formation of a mixture of the major product ‒ dimer 2a, and minor indene 3a (Table 1, entry 1). The target dimer was isolated in 74% yield as a single diastereomer. Its structure was reliably confirmed by X-ray analysis

• ortho-methyl substituent in the benzylidene fragment. In this case, along with conventional reaction products ‒ dimer 2r and indene 3r, unexpectedly the cyclobutane 5, a product of the formal [2 + 2] cycloaddition, was isolated in low yield (Scheme 1); its structure was confirmed by single-crystal X-ray

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -ray analysis revealed the presence of the expected [N–H···O] hydrogen bonds between the secondary ammonium station and the crown-ether macrocycle, but also additional [C–H···O] hydrogen bonds involving the benzylammonium methylene groups (see Figure 4). Interestingly, the presence of the directional

• -workers [46]. They reacted the amine axle 11 with the axially chiral macrocycle (rac)-12 in a mixture of dichloromethane and trifluoroacetic acid in order to generate the pseudorotaxane (rac)-13. Then, an isocyanate stopper was added for the formation of the [2]rotaxane (rac)-14 in a yield of 42%. The X

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• particular, compound 1 also has a tetracyclic skeleton with a methyl group at C-4. The absolute configuration of 1–3 was determined by X-ray analysis. Herein, we report the isolation, structure elucidation, and bioactivities of these compounds. Results and Discussion Compound 1 was isolated as a white powder

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• , and alkyl at the para-position of the phenyl ring and the corresponding oxyaminated products were obtained in excellent yields and good enantioselectivities (4a–f). The single crystal X-ray analysis of the product 4a established the absolute stereochemistry which was found to be S (Figure 1) [62

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• Information File 258: General information, synthesis procedures, and spectral data. Acknowledgements The authors are grateful to Mr. S. Belyakov (Latvian Institute of Organic Synthesis, Riga, Latvia) for performing the X-ray analysis. Funding This work has been accomplished with financial support provided by

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• resonating at 4.49, 1.53, and 2.02 ppm, respectively, in the COSY spectra of 10. The cross peak (δ 4.49 ppm) between H-6 and H-7 showed a strong correlation, which clearly supports the trans relation of the proton H-7. Furthermore, its structure was unambiguously confirmed by single crystal X-ray analysis

• reported. Supporting Information File 266: Additional experimental and computed data. Acknowledgements The authors are indebted to the Atatürk University for its support. We would also like to thank Professor Ertan Sahin for performing the X-ray analysis. Funding This study was funded by the Research Fund

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• of an unexpected rearrangement this structural assignment was still erroneous, and the correct structure 3 was finally established by X-ray analysis of its chromic acid diester [6]. The patchoulol synthase (PTS) has been purified from plant leaves and shown to convert farnesyl diphosphate (FPP) into

Host–guest interaction and properties of cucurbit[8]uril with chloramphenicol

• Lin Zhang,
• Jun Zheng,
• Guangyan Luo,
• Xiaoyue Li,
• Yunqian Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 2832–2839, doi:10.3762/bjoc.17.194

• consistent with our single-crystal X-ray analysis of CPE@Q[8] shown in Figure 2. IR spectroscopy Figure 6 shows the IR spectra recorded for Q[8] (a), CPE (b), a physical mixture of Q[8] and CPE {n(Q[8])/n(CPE) = 1:1} (c) and the CPE@Q[8] inclusion complex (d). By comparison, spectrum (c) is a simple

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• testing (IC50 values less than 10 μM are marked with an asterisk, while a dash denotes an IC50 value higher than 100 μM). Supporting Information Supporting Information File 348: Synthetic procedures, analytical data, X-ray analysis details, and copies of spectra. Funding The authors acknowledge the

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• were characterized by 1H NMR, 13C NMR, HRMS, and 19F NMR (5b, 5c and 5h) spectroscopy wherever applicable. The structures of compounds 3, 5c and 7b were unambiguously confirmed by single crystal X-ray analysis diffraction method. Single crystal X-ray structure analysis supported the formation of the

• . The structure of metronidazide 3 was unambiguously confirmed by single crystal X-ray analysis (Figure 3). The next step was carried out by using “click” chemistry involving the 1,3-dipolar cycloaddition reaction between metronidazide 3 and alkyne derivative 4a in the presence of CuI and Hünig’s base

• + H)+ supported the structure of 1H-1,2,3-triazole compound 5c. Single crystals of 1H-1,2,3-triazole compound 5c were grown from slow evaporation of MeOH. The structure of 1H-1,2,3-triazole compound 5c was unambiguously confirmed by single crystal X-ray analysis (Figure 4). Synthesis of carboxylate