Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• and di-tert-butyl azodicarboxylate (Scheme 22) [45]. An added benefit to these products is that they possess an intramolecular hydrogen bond acting as a stabilizing factor and products 68 were prepared in good to very good yields and excellent enantiomeric purities. Based on the authors’ design

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• that the alkoxy groups in compound 10, which are positioned para or ortho to the reacting site, play an important role in the Scholl reaction to form compound 3. Similar substrates, where the alkoxy groups are replaced by hydrogen atoms or a 4-tert-butyl group, did not yield product 3 under similar

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• hand, we turned our attention to the synthesis of PhFlOP-based compounds through a Cs2CO3-facilitated nucleophilic substitution with substituted carbazoles as the nucleophiles (Scheme 2). For example, tert-butyl, bromo, carbazolyl, or phenyl substituents were introduced into the carbazoles. To our

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• salts [34]. Under these conditions, N-benzyl-4-methylbenzenesulfinamide (6aa) was not observed, and N-benzyl-p-toluenesulfonamide (5aa) was isolated in 29% yield (Table 1, entry 4). To prevent the regeneration of tert-butyl 3-(p-tolylsulfinyl)propanoate (4a) and employ milder conditions, a study was

• is more favorable at higher temperatures [4]. Due to the reversibility of the retro-Michael addition, an experiment was carried out using an excess of tert-butyl 3-(p-tolylsulfinyl)propanoate (4a) leading to an increase in the yield of the corresponding sulfonamide 5aa by 38% (Table 1, entry 6). A

• electrophilic amination reaction afforded sulfonamides 5aa, 5ba, 5da, and 5ea with moderate yields. However, no amination product was detected with tert-butyl 3-(benzylsulfinyl)propanoate (4c). This result suggests that aliphatic β-sulfinyl esters may not possess sufficient nucleophilicity to react with the

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• isoxazole ring, both with electron-donating and electron-withdrawing groups, and the tert-butyl-substituted isoxazole 1j, we proceeded to obtain dicarboxylic acids 6 (Scheme 2). The isomerization of isoxazoles 1 into diacyl chlorides 2 was achieved by applying the conditions for the isomerization of 3-aryl

• not isomerize at room temperature, which is typical for highly sterically congested isoxazoles containing a 3-tert-butyl substituent [26]. The mechanism of such isomerizations of isoxazoles has been previously discussed using DFT calculations [25][26], which revealed the formation of an isoxazole–Fe

• isomerization to 3-aryl-2H-azirine-2,2-dicarbonyl dichlorides followed by their fast reaction at the same temperature with O- and N-nucleophiles. 3-Aryl-2H-azirine-2,2-dicarboxylic acids were prepared in 64–98% yield, whereas 3-(tert-butyl)-2H-azirine-2,2-dicarboxylic acid could not be obtained by this method

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• instance, when the bulky tert-butyl ester sulfoxonium ylide was used, the fluoroalkyl product 3f was obtained in 82% yield. A 60% yield was obtained for 3g when the reaction was carried out with the cyclopentyl ester ylide derivative. The allyl sulfoxonium ylide reacted to produce 3h in an excellent 92

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• order to lead to the expected fluorinated tetrahydropyridazines (Figure 4). Results and Discussion First, the difluoro- and trifluoromethylated hydrazones 3a–f were synthesized by condensing the corresponding hydrazide with the fluorinated aldehyde hemiacetal 2a or 2b (Scheme 2). Benzyl and tert-butyl

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• , was not ruled out. In 2013, Nevado and co-workers used (R,R)- and (S,S)-tert-butyl lactate iodotoluene difluoride (8) for the aminofluorination of alkenes toward the synthesis of enantiomerically pure β-fluorinated piperidines 6 (Scheme 3) [28]. A range of enantiomerically pure fluorinated piperidines

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• different electronic properties (18, 25–41, Figure 6) were screened as catalysts for the sulfa-Michael addition of tert-butyl benzylmercaptan 42 to phenyl vinyl sulfone (43). Without the addition of a porphyrin, no product was formed. Among the non-alkylated porphyrins (18, 25–32) only the ones containing

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• studies, we employed benzaldehyde derivatives with various stereoelectronic decoration, excluding aliphatic ones due to their decreased reactivity resulting in failures to proceed [24][25][26][27]. Commercially available isocyanides utilized were cyclohexyl and tert-butyl isocyanide. Notably, an isolation

• importance of the tert-butyl and cyclohexyl substituents in the imidazole can be deduced. According to the IC50 results presented in Figure 1, it can be seen that all cyclohexyl-substituted derivatives tested show activity. In contrast, those carrying the tert-butyl group are inactive, except for 18i and 18a

• , which show moderate and low activity, respectively. The modification of this substituent is seen when comparing the analogous derivatives 18d and 18c; 18h and 18g; 18b and 18a; 18f and 18e, where the replacement of cyclohexyl by tert-butyl leads to a loss of activity in each case. Concerning the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• colleagues firstly demonstrated that the decomposition of tert-butyl hydroperoxide (TBHP) by Co(II) naphthenate proceeds via a chain mechanism, leading to the formation of tert-butoxy and tert-butylperoxy radicals (Scheme 4) [24]. When cyclohexene (1) and oct-1-ene (3) were added, the corresponding products

• , phenylacetonitrile (55), with TBHP under Cu-catalysis led to a mixture of the oxidation products 56–59 including tert-butyl perbenzoate (57, Scheme 21) [25]. This discovery was later used to develop the synthesis of tert-butyl perbenzoates 61 from phenylacetonitriles 60 and TBHP (Scheme 21) [64]. The process was

• carried out without solvent and at room temperature, using copper(II) acetate as the catalyst. The reaction pathway of tert-butyl perbenzoate synthesis from benzyl nitriles 60 involves the formation of intermediate D. The Kornblum–DeLaMare rearrangement of peroxide D gives benzoyl cyanide E, which is

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• reactions occurred under mild conditions and without any need of transition-metal catalysts. In 2023, Wu and colleagues successfully synthesized a range of meta-substituted biaryl ethers. The reaction involves phenols 61 and cyclic diaryliodonium salts 73, dissolved in tert-butyl alcohol, in the presence of

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• for this reaction. By replacing cyclohexyl isocyanide with tert-butyl- and isopropyl isocyanide, the corresponding products were obtained with similar yields. To investigate the reactivity of other cyclic imines in this protocol, we performed the reaction of triazolobenzodiazepine with gem-diactivated

• mass spectrometry. Taking 4h as an example for the analysis of its structure, in its 1H NMR spectrum, one singlet signal appears at δ = 0.67 (9H) corresponding to the three methyl groups in the tert-butyl substituent. A singlet at δ = 2.39 (3H) is assigned to the protons of the CH3-group on the phenyl

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• oxidize the substrate, which reacted with the 3-methoxyaniline and tert-butyl isocyanide affording the α-aminoamidine, albeit inefficiently. Besides, the role of GO in the 3C Ugi reaction remained unclear. Actually, the iminium ion formed after the oxidation is already quite activated to react with

• synthetic process in a one-pot manner, adding all the components from the very beginning. So, the blue-light-promoted reaction between N-Ph-THIQ, 3-methoxyaniline and tert-butyl isocyanide in the presence of BrCCl3 was extensively optimized by varying several parameters, such as solvent, relative quantity

• -methylaniline step by step (Scheme 4). While the 3C Ugi-type reaction between iminium ion 1a, p-methylaniline and tert-butyl isocyanide gave product 2p in good yield, when the α-aminoamidine was subjected to the oxidation–cyclization step, the starting material was completely converted, but 3p was not isolated

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• a methyl group, for instance, increased the barrier by 1.4 kcal·mol−1, a phenyl group by 1.7 kcal·mol−1, and a tert-butyl group by more than 2 kcal·mol−1 (Table S1, Supporting Information File 1). This observation is consistent with reports in the literature [24][53][54][55][56]. Based on this

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• , and 4ma. Whereas compound 4ja and 4ma showed an ideal single crystal behavior, compound 4fb showed a dynamic disordered structure due to intramolecular vibrations in the unit cells, particularly because of the presence of the tert-butyl group, which can assume any rotation angle [24]. Nevertheless

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• . For example, Liu and colleagues demonstrated the electrochemical oxidation of benzylic C–H bonds to ketones using tert-butyl hydroperoxide as the radical initiator [14]. This method was applied to functionalize bioactive molecules, with celestolide, ibuprofen methyl ester, and papaverine being

• oxidized at the benzylic position in good yields. A gram-scale test was conducted to confirm the potential for large-scale applications. According to the authors, the electrochemical oxidation of t-BuOOH at the anode leads to a tert-butyl peroxyl radical that activates the C–H bond at the benzylic position

• generated tert-butyl peroxide to form an allylic peroxide, which ultimately transforms into an enone upon elimination of t-BuOH (Scheme 24). One year later, they developed an electrochemical transformation closely related to their electrochemical allylic oxidation, i.e. the oxidation of unactivated C(sp3)–H

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• , enhances charge transfer by stabilizing the mesityl moiety. Conversely, the introduction of tert-butyl groups increases the life time of the excited state [52][53][54][55][56]. As a consequence, the PC IV is a strong oxidant in the excited state and displays unique oxidizing properties (E1/2[*PC+/PC

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• -triazole, thiazole, or pyridine were synthesized by the reaction of 3,5-di-tert-butyl-o-benzoquinone or 3,5-di-tert-butyl-6-methoxymethylcatechol with different heterocyclic thiols. The S-functionalized catechols were prepared by the Michael reaction from 3,5-di-tert-butyl-o-benzoquinone and the

• corresponding thiols. The starting reagents such as substituted 1,3,4-oxadiazole-2-thiols and 4H-triazole-3-thiols are characterized by thiol–thione tautomerism, therefore their reactions with 3,5-di-tert-butyl-6-methoxymethylcatechol can proceed at the sulfur or nitrogen atom. In the case of mercapto

• -derivatives of thiazole or pyridine, this process leads to the formation of the corresponding thioethers with a methylene linker. At the same time, thiolated 1,3,4-oxadiazole or 1,2,4-triazole undergo alkylation at the nitrogen atom in the reaction with 3,5-di-tert-butyl-6-methoxymethylcatechol to form the

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• proved by X-ray studies. Assuming the mechanism of addition is similar in the case of other nucleophiles, the configuration of others was assigned by analogy. More sterically demanding di-tert-butyl thiomalonate (2) reacted in a similar fashion as the dibenzyl thiomalonate (1), leading also to desired

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• N-tert-butyl-α-phenylnitrone (PBN) afforded the aziridine product 3b in 60% NMR yield (Scheme 4d), suggesting a radical pathway was unlikely to be operative. An 1H NMR experiment was carried out to probe the speciation of 2a in HFIP, and we observed that 2a underwent reversible ligand exchange with

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• dimethyl sulfoxide (DMSO), methanol (MeOH), methyl tert-butyl ether (MTBE), and n-hexane. Measurements in triplicates. 0.5–1% only for MC and CMC. PEG, MC, CMC: % % w/v. Other: % % v/v. Note: 2% PEG-8000 is present as a standard component in all reactions, unless otherwise stated. n.d.: not determined

• ), methylcellulose (MC), carboxymethylcellulose (CMC), choline chloride/urea (ChCl/urea), choline chloride/glycerol (ChCl/glycerol), and betaine/ethylene glycol (betaine/EG). The reference experiment is labeled as shaded bars. B) represents dimethyl sulfoxide (DMSO), methanol (MeOH), methyl tert-butyl ether (MTBE

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• azodicarboxylate reagents. In the attempt to recycle catalyst 28 for the reaction between ethyl 2-oxocyclopentanecarboxylate (25) and di-tert-butyl azodicarboxylate (26) (Scheme 8), a decline in catalytic activity was initially noticed. While this could be attributed to the nucleophilic deactivation of thioureas

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• )hydrazine ((Me3Si)2N–N(SiMe3)2, 10) undergoes ultraviolet light-induced homolysis of the N–N single bond of 10 to form bis(trimethylsilyl)aminyl radical ((Me3Si)2N•, 11). The aminyl radical 11 adds to tert-butyl isocyanide to form the corresponding imidoyl radical 2 (R = t-Bu, E = (Me3Si)2N), as confirmed

• yields. In the case of tert-butyl and benzyl isocyanides, the substituents on the nitrogen of imidoyl radical 2 (R = t-Bu or PhCH2, E = Et2P or Ph2P) were eliminated to give cyanophosphines (R’2P–CN, Scheme 7) [38]. On the other hand, we attempted a photoinduced addition of phosphorus–phosphorus

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178