1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• at room temperature to form the expected Diels–Alder adduct 32, while non-cyclic vinyl disulfones require heating to 80 °C for 20–48 h. Deoxygenation of the epoxide and desulfonylation with sodium amalgam affords barrelene (33) in an excellent overall yield from oxepin. The chlorinated 1,4-dithiin

• carbons of the diene to allow a Diels–Alder-type reaction. Chou and co-workers developed an elegant synthesis of a 1,4-dithiane-fused sulfolane 45 (Scheme 9b) [56]. Oxidation of the 1,4-dithiane-fused sulfolane 44 to the hexoxide and heating to 130 °C afforded the pure 1,4-dithiane-tethered diene 45 via

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• heating module was used for the preparation of isocoumarin products 3.) Significance of isocoumarins (a), classic methods for the synthesis of isocoumarins (b) and reaction design (c). Scope of enaminones. Scope of iodonium ylides. Gram-scale reaction (a) and synthetic transformation (b). Proposed

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• of tubes and sheets. For these particular samples, the freeze-dried mixtures produce a spherical material in the heating step, covered by a fragile and brilliant layer but possessing a highly porous inner structure. This thin layer is more evident for the β-csp sample produced using the liquid path

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

• , screening a variety of conditions including the use of stoichiometric and substoichiometric amounts of Lewis acids such as AgOTf and BF3·OEt2 with and without heating (23 and 80 °C) did not afford any targeted aza-Nazarov product 30 (for details see Table S1 in Supporting Information File 1). The reactivity

Modern flow chemistry – prospect and advantage

• Philipp Heretsch

Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3

• stage in the last decades [1]. Originating from the petrochemical industry, where it enabled high productivity and scalability even for the most standard processes of heating, cracking, and refining of crude oil to bulk chemicals [2], it has since entered the production of pharmaceuticals and other fine

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• feature a bicyclo[3.1.0]hexene core which photochemically arises from 1,3-cyclohexadiene precursors, tridachiapyrone A or 9,10-deoxytridachione, as demonstrated by Ireland [16][17]. In turn, the ring system arises from α-tetraenyl-α’-methoxy-γ-pyrone precursor 1a upon heating through 6π-electrocyclization

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

• was selectively reduced in the presence of LiEt3BH, while the Peterson adduct was eliminated concurrently, upon heating. Finally, treatment with H2SO4 allowed total deprotection of the MOM ethers, leading to the formation of principinol D, in complete correspondence with reported spectral data

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

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

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• cyclohexanone (as well as other cyclic ketones) which delivered spiro-annulated 2-benzoxepines (such as 2a) along with a minor byproduct 3a identified by 1H NMR as the product of formal insertion of the rhodium(II) carbene species into the O–H bond of cyclohexanone enol form. This minor byproduct, on heating at

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. The use of homopropargylamine (18) in the reaction of 1 with aldehyde 3a abolished the facility of the intramolecular azide–alkyne click reaction which now required heating at 120 °C for 2 hours for the eight-membered (1,5-diazocane) ring to form (notably, the presence of the azide–alkyne

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• (Table 1, entries 2–4) superior to 86% yield for 3 h (Table 1 entry 1), and followed by decarboxylative [3 + 2] cycloaddition with the second equivalent of compound 1a and olefinic oxindole 4a under reflux heating for 12 h. It indicates that the one-pot reaction process with EtOH and iPrOH afforded the

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

• to decreased reaction yields (Table 2, entries 2–5). The reaction with diazooxindole 2b having an electron-withdrawing group (-Br) in the C(5) position (Table 2, entries 2 and 3) required additional heating to obtain the product 3ab. On the other hand, the reaction of diazooxindoles 2c and 2d (Table

•  2, entries 4 and 5) bearing an EDG (electron-donating group) in positions N(1) (Bn-) or C(5) (MeO-) did not require heating and proceeded under conditions similar to the ones with unsubstituted diazooxindole 2a. Next, we investigated the substrate scope using different FPDs 2 (Table 3). FPDs 1а–f

• the yield of the target reaction product, without affecting the reaction rate (Table 3, entry 7). Quinoxaline-annulated FPDs 1h–j required heating, as these compounds reacted too slowly at room temperature (Table 3, entries 8–10). It should be noted that FPDs 1h–j gave yields of the target products

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

• derivatives involves the intramolecular cyclotrimerization of C=N bonds in a suitable trisimine precursor (Scheme 1). Previously, 3O-TAADs 2 were prepared by cyclization of corresponding trisoximes 1 [21]. However, this reaction is slow and reversible (upon heating adamantane structure 2 reverts to the tris

• 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

• , treatment of adamantanes 4a and 4b with excess hydrazine (100–200 equiv) upon heating did not lead to any conversion. Also attempts to deprotect Boc-derivatives 4c, 4e, 6a, and 8a with trifluoroacetic acid or hydrochloric acid (in water or dioxane) were not successful and led to complex mixtures of products

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• . Oxidation of the latter compound to the α-keto-β-hydroxy ester IV using DMDO and subsequent heating in PhCF3 triggered an α-ketol rearrangement which led to ketol V. Diastereoselective reduction gave α,β-dihydroxyester 35 which was converted to (−)-jiadifenoxolane A (36) in five further steps. Palau’amine

• was synthesized by a Horner–Wadsworth–Emmons reaction of phosphonate 48 with aldehyde 47. Enantiopure aldehyde 47 was easily accessible from oxazolidinone 46 via Evans-aldol chemistry [23]. Heating of the α-ketoester 49 led to the highly substituted cyclopentanol 50 in a good dr of ≈5:1 (minor

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• kinetically controlled product when no Et3N is added into the solution (entry 5, Table 2). In contrast, pure (R,S) diastereomer was obtained when the solution containing 1 mol equiv of Et3N was kept for 72 h under slight heating (40 °C, entry 6); though in the expense of the yields decrease (a significant

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

• structures of the obtained compounds were elucidated by NMR and mass spectrometry. The reaction between 1,5-diphenyl-4-acetyl-3-hydroxy-3-pyrrolin-2-one (4a) and 4-methoxybenzylamine (9a) was chosen to optimize the reaction conditions, such as the reactant ratio and solvent. Heating 2-pyrrolidinone

• yield. The yield of 10aa could be increased to 62% when substrate 4a was reacted with the amine 9a in DMF at 95 °C (Table 4), meaning that the reaction does not require an acidic medium. Ethanol was also used as green solvent to test the above model reaction. As compared to CH3COOH, heating compounds 4a

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

• catalysts (Pd, Rh, Fe, etc.) were employed to boost the reactivity of NXS (Scheme 1b) [32][33][34][35][36][37][38][39][40][41][42][43]. However, the use of toxic and expensive metals, high catalyst loading, and heating conditions are some sheer hurdles to achieving sustainability. Among notable other

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• (Scheme 7) [27]. Synthesis via P–N bond formation Since 1980, new strategies for the synthesis of γ-phosphonolactams and γ-phosphinolactams have been explored via cyclization by P–N bond formation [28]. Kleiner prepared 1-aryl-2-methyl-1,2-azaphospholidine 2-oxides 46 in 40–78% yields by heating 3

• azaphospholidine 2-sulfide 52 in only 21% yield by heating at 200 °C for 60 h (Scheme 8) [28]. In 1982, Collins and co-workers prepared both 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 56 and 2-sulfide 60 through heating zwitterionic 2-aminobenzyl(phenyl)phosphinic acid 54 and 2-aminobenzyl(phenyl

• -dihydrobenzo[d][1,2]azaphosphole 2-oxide (55), which was further alkylated with alkyl halides in the presence of NaH, affording 1-alkyl-2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 56. Alternatively, under heating, methyl 2-aminobenzyl(phenyl)phosphinate (53) underwent a transmethylation from the O

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• starting bromoacetate at rt or on heating to 50 °C. The further substitution reactions, during peptoid elongation, were carried out in a 1:1 MeOH/H2O mixture (1.25 M) at 60 °C, using three equivalents of the Boc-protected hydrazine reagent. These distinct substitution conditions, together with standard

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• -methylthiopyrimidines with m-CPBA and oxone and found that oxone gave better results, so we have chosen it for this reaction. Thus, heating compound 3 in dimethylformamide at 40 °C for 0.5 h with oxone gave compound 5 in 80% yield. In the NMR spectra of compound 5, the peaks of the methylsulfonyl group are downfield

• shifted by 0.8 ppm and 24.8 ppm in the 1H and 13C NMR spectra, respectively, in comparison with the signals of the methylthio group of compound 3 (see Supporting Information File 1, Figures S1, S2 and S5, S6). Heating compound 5 with primary and secondary amines in dimethyl sulfoxide at 50–70 °C for 0.5 h

• gave the corresponding (2-substituted pyrimidin-4-yloxy)acetates 6–9. In order to replace the 2-methylsulfonyl group with a hydroxy group, we tested several techniques. It was found that heating compound 5 with water in dimethyl sulfoxide at 100 °C or boiling for 1 h in water led to hydrolysis of both

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• obtain the corresponding sulfinate in limited yield, the decomposition of this compound after several days at 4 °C, and within a few minutes under heating deemed its applicability impractical. After this first step, we proceeded to test the nucleophilic substitution between our perfluoroalkylsulfinate

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• was still not satisfactory. Therefore, not only the temperatures, but also the residence time was gradually changed (Figure 2). At 70–90 °C and a residence time of 50.0 min the best results were observed. However, heating to 80–90 °C provided increasing amounts of azoxybenzene, which is a known side

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

• tetrahydrofuran (THF), and the resulting mixture was maintained at reflux. After heating for 2 h, completion of the reaction was indicated by both the colour change of the reaction mixture and TLC (thin-layer chromatography) analysis. The proposed cycloadduct was isolated after recrystallization from methanol

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• synthetic organic chemistry. Advantageously, more difficult substrates or limitations of the conditions can be overcome by the change of the reaction methods. One of the emerging synthetic methods is mechanochemistry [4][5][6][7], a greener alternative to carry out synthesis which complements heating

• . Dibromide 42 was prepared by Diels−Alder reaction of anthracene (13) and 2,3-dibromo-N-methylmaleimide (41) (Scheme 3). Heating of the reactants at 180 °C for 10 min provided the required cycloadduct 42 (98% yield). When 42 was subjected to Zn/Cu debromination in a ball mill in the presence of anthracene

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• membrane-like environment. Along these lines, no product formation was detectable when UbiA-297 was denaturated by heating prior to the assay (control), nor when a MenA-1335 (Maribacter sp. MS6) homolog was tested. Furthermore, different pH values and extended incubation times were investigated, however

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• Conrad Kuhwald Sibel Turkhan Andreas Kirschning Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.18.70 Abstract Inductive heating has developed into a powerful and rapid indirect heating technique used in various fields of

• chemistry, but also in medicine. Traditionally, inductive heating is used in industry, e.g., for heating large metallic objects including bending, bonding, and welding pipes. In addition, inductive heating has emerged as a partner for flow chemistry, both of which are enabling technologies for organic

• synthesis. This report reviews the combination of flow chemistry and inductive heating in industrial settings as well as academic research and demonstrates that the two technologies ideally complement each other. Keywords: catalysis; enabling technologies; flow chemistry; inductive heating; multistep