(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• ), deprotection, decarboxylation, oxidation, nitrogen extrusion (to cyclobutadiene) and Diels–Alder reaction yielded annulated tricycle 164. Further intramolecular [2 + 2] cycloaddition formed cubane precursor 165. From diketone 165, 1,3-cubane 166 was obtained by Favorskii ring contraction followed by

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

• conversion in situ, triggered by thermal activation, photoirradiation or redox control. Beside well-established reactions involving the elimination of carbon-based small molecules, i.e., retro-Diels–Alder and decarbonylation processes, the late-stage extrusion of chalcogen fragments has emerged as a highly

• ultimate elimination of chalcogen fragments upon thermal activation, photoirradiation and electron exchange. Keywords: arenes; chalcogens; extrusion; fused-ring systems; precursor approach; Introduction π-Conjugated polycyclic compounds (π-CPCs), including polycyclic aromatic hydrocarbons and their

• π-CPCs relies on the extrusion of carbon monoxide (CO) from soluble precursors incorporating bridging ketone fragment(s). In contrast with the thermal activation required in retro-Diels–Alder reactions, photoirradiation of α-diketones triggers a Strating–Zwanenburg decarbonylation leading to the

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• -unsaturated phthalimide 33a. Simultaneously, radical III of the catalyst was also formed, accompanied by the extrusion of CO2. Subsequently, the alkyl radical A added to the carbon–carbon triple bond of enynal 32g, resulting in the formation of a vinyl radical intermediate B, followed by a 5-exo-trig

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• sulforhodamine B were purchased from Sigma-Aldrich, USA. 4-Amino-3-hydroxy-1-naphthalene sulfonic acid was purchased from Fluka, India. Sulfuric acid was purchased from ACROS Organics, Belgium and diethyl ether was purchased from VWR-Prolabo Chemicals, Belgium. Liposomes preparation, extrusion, and purification

• using a rotary vacuum evaporator (Heidolph, Germany). Then, the aqueous phase (SRB containing buffer) was added to the dry film and the mixture was sonicated at 60 °C under a nitrogen stream to generate vesicles. The SRB-loaded liposomes were subjected to extrusion through polycarbonate filter membranes

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• iodobenzene gave 19, and extrusion of SO2 gave 20. In 2010, Moriarty revisited their earlier transformation and reported that the metal-free intramolecular cyclopropanation of 10 to 11 could be achieved in an improved 95% yield by performing the reaction at room temperature rather than 0 °C [11]. The reaction

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• aldehyde with thioglycolic acid and aminopyrazole, followed by the extrusion of sulfur from the resulting thiazepine [20] (method C). The three-stage synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones, involving the preparation of 3-aryl-N-(1H-pyrazol-5-yl)propiolamides (method D), also leads to the

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• cyclization event would be triggered using their innate functionality, namely the α-amino carboxylate, through photoredox-mediated oxidative activation and CO2 extrusion, without the need for acid prefunctionalization to the redox-activated ester. Consequently, a technique involving direct generation of α

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• the ring strain involved in the enthalpy term disfavors it) shows the opposite trend. This means that the activation free energies are decreasing from 47 to 23 kJ·mol−1, respectively. Spontaneous co-catenation (or thiophile-assisted when a P(III) compound is added) extrusion of sulfur from thiirane

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

• cyclization (Scheme 51A) [93]. The reaction starts with the coordination of the Rh catalyst to the propargyl alcohol 198. In the presence of a base, the rhodium–alkynyl reagent is generated with the concomitant extrusion of benzophenone. Finally, the alkynylation of the enone is followed by the cyclization

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• adds to the diazo compound 5 under formation of zwitterionic Int1 (ΔG = 5.2 kcal/mol). Afterwards, copper carbene complex Int2 is formed after extrusion of nitrogen. The transition state of this metal carbene formation TS1 was calculated with an activation free energy of 16.4 kcal/mol (Scheme 5). Int2

• Int4_3 and Int4_4 without further intermediates (Scheme 7 and Scheme 8). Extrusion of a catalyst yields Pr1, Pr2, Pr3 and Pr4 as presented in Scheme 8. As shown in Table 2, the formation of the enantiomeric set Pr1 and Pr3 (ΔG = −44.6 and −44.1 kcal·mol−1) is slightly more favorable than the formation of

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• synthesis of combretastatin D-1 (1) using the flash vacuum pyrolysis (FVP) technique, which consisted on the contraction of 16-membered sulfone derivatives, by extrusion of sulfur dioxide [58]. The synthesis of the required sulfone was initiated by a Horner–Wadsworth–Emmons reaction between the aldehyde 52

• sulfone 134 using m-CPBA [63] followed by contraction of the macrocyclic ring by extrusion of SO2 using FVP gave compound 28 together with macrocycle 135, obtained from the simultaneous extrusion of SO2 and CO2. Cleavage of the methyl ether in 28 gave the desired product 2 in 0.6% overall yield after 10

• macrocyclization using SO3·pyridine [68] gave the corresponding thioether 151, which was oxidized to the cyclic sulfone 152 using m-CPBA. Extrusion of SO2 by FVP followed by demethylation of the formed macrolide furnished the compound 154 which can be converted in combretastatin D-1 (1) by known methodologies [43

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• , Colombia 10.3762/bjoc.18.150 In the past ten years, the use of mechanochemical techniques (e.g., grinding, milling, extrusion, pulsed ultrasonication, resonant acoustic mixing, etc.) have widespread in the field of organic chemistry, enabling the development of new and more sustainable protocols for

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• into new modes to activate matter by force (e.g., twin-screw extrusion [71], resonant acoustic mixing [72], vortex fluidic mixing [73], laminar flow [74], etc.) will continue to unveil similarities and complementarities, rather than disparities, between the ways polymer and small molecule

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• ; sulfonylation; Introduction Mechanosynthesis of organic molecules and materials using mechanochemical techniques such as ball milling, extrusion, grinding, etc. [1][2][3] have enabled the development of known and new chemical transformations in a more sustainable fashion [4]. Commonly, mechanochemical

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• [57][58][59][60][61][62][63][64][65]. Results are summarized in Table 2. Triphenylphosphine and triethyl phosphite could be used interchangeably in the sulfur extrusion step. However, in most cases the co-elution of enaminones 15 with phosphorus-derived byproducts during chromatographic purification

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• -catalyzed trifluoromethylchlorosulfonylation of unactivated alkenes 4 under photochemical conditions. When used in place of [Cu(dap)2]Cl, ruthenium-based, iridium-based, and eosin Y catalysts promoted the trifluoromethylchlorination of alkenes with the extrusion of SO2 (e.g., product 6). Studies were

• – is stabilized by the copper complex. The alkyl radical reacts with LnCuII-SO2Cl to deliver the target product 5. A mechanistic study demonstrated that [Cu(dap)2]Cl can coordinate with the reactive intermediate SO2Cl and suppresses the extrusion of SO2. Thus, [Cu(dap)2]Cl achieves a unique

An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone)

• Jochen Löblein,
• Thomas Lorson,
• Miriam Komma,
• Tobias Kielholz,
• Maike Windbergs,
• Paul D. Dalton and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2021, 17, 2095–2101, doi:10.3762/bjoc.17.136

• ], micro-extrusion [7] and selective laser sintering have all been used to fabricate clinical implants [6][7]. Other emerging 3D printing technologies can also fit the prerequisites described above, including melt electrowriting (MEW) [8]. This technology is based on the direct-writing of ultra-fine (800

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• alkyl radical with formaldehyde hydrazone, which resulted in hydrazide 74 that could afford formal hydromethylated compounds 75 after the extrusion of nitrogen and sulfinic acid (Scheme 28) [95]. The hydrazone was generated in situ due its instability, and a simple exchange of the solvent from THF to

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• more general route to [2.2]metaparacyclophane (3) derivatives involves synthesis of 2,11-dithia[3.3]metaparacyclophane followed by the extrusion of sulfur, or more commonly sulfur dioxide, and this has become the de facto route to these molecules [25][37][38][39][40][41][42][43]. Even though this

• but these are substrate specific [71][72]. Conclusion Currently, substituted [2.2]metaparacyclophanes are synthesized through a long sequence involving either high temperature extrusion of sulfur dioxide or photoextrusion of sulfur. We have found a serendipitous route to a disubstituted [2.2

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• % mortality rate with DOVLP28-mix. This protection is significantly higher compared to the first results using fish oil. Both treatments using commercial binders indicate that it is possible to administer it in the pellets. However, it is crucial to state that pellets usually undergo pelleting or extrusion

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• N2 extrusion. Therein, the formed [5,6]-opened adducts are transformed into [6,6]-closed isomers, which are more thermodynamically stable. While the range of reagents used in nucleophilic cyclopropanation with stabilized carbanions is mainly limited to malonates, the range of cyclopropanating agents

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• high amounts of the undesirable isoindigo 9a [32] (route c). In order to accelerate the Eschenmoser coupling reaction and to enhance the reaction yield (route b) an addition of a suitable thiophile assisting the sulfur extrusion should be beneficial [36]. Therefore, we tested two P(III) compounds as

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tricyclic compound 25, which led to the synthesis of (±)-hirsutene (14) [22] (Scheme 1A). Refluxing azo compound 22 in acetonitrile generated the proposed biradical intermediate 23 through nitrogen extrusion. This intermediate underwent isomerization to 24 and intramolecular diyl trapping through a [3 + 2

• trimethylenemethane diyl [3 + 2] cycloaddition of 40 led to the formation of angular fused triquinane 41 in 98% yield. The authors suggested that an intramolecular cycloaddition of the diazo group and allene 38 produces tetrahydrocyclopentapyrazole 39. Extrusion of nitrogen from the newly formed 39 produces diyl 40

• natural product syntheses that feature the all-carbon [3 + 2] cyclization as the key reaction, reported before 2011. (A) TMM cycloaddition of diyl 24 resulted from dinitrogen extrusion/isomerization is used to prepare tricycle 25, which is a synthetic precursor of (±)-hirsutene (14) [22]. (B) Synthesis of