Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• reaction; the stereoselectivity of product 17j drastically dropped. The scope for the pre-nucleophile showed that phenyl-substituted 16b provided 17k in 94% yield with high diastereoselectivity, albeit with decreased enantioselectivities. Methyl ester 16c and tert-butyl ester 16d were also applied to the

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• -aminopyrazole 2. Compounds 3ab and 3ad were obtained in a comparable yield (54 and 46%) from 1,3-dimethyl-1H-pyrazol-5-amine (2b) or 3-methyl-1-(p-tolyl)-1H-pyrazol-5-amine (2d). On the other hand, 1,3-diphenyl-1H-pyrazol-5-amine (2c) provided the corresponding product 3ac in much lower yield (16%). If a tert

• -butyl group is present in the C-3 position of the pyrazole as in the case of substrate 2e, the reaction did not take place, likely due to a considerable increase in steric hindrance. We also attempted to synthesize 4-(alkenyl)-5-aminopyrazoles using an acyclic ketone, such as acetone, but unfortunately

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• macrolactamisation [21]. The syntheses of required unit A [28], C [29][30], and D [31] building blocks were accomplished as described previously. tert-Butyl-protected leucic acid 14 and Fmoc-β-aminopivalic acid (15) were connected by Steglich esterification (Scheme 2) and after cleavage of the tert-butyl ester group

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• except the preparation of the aminoaniline building block tert-butyl (2-amino-5-bromophenyl)carbamate (5), which was prepared by Boc-protection of the 5-bromo-2-nitroaniline (6) and subsequent reduction of the nitro group (see Supporting Information File 1, section II.1). Cross-coupling reactions Stille

• halogenated N-acetyl diazocines according to the procedure of Maier et al. [34] with tert-butyl carbamate resulted in the formation of Boc-protected amino-substituted N-acetyl diazocine 19 in a yield of 72%. However, the reaction only took place if iodo N-acetyl diazocine 3 was used as starting material

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• interaction of 2,3,3-trimethylindolenine with 3,5-di(tert-butyl)-1,2-benzoquinone leads to the formation of indolo[1,2-a]indoline derivatives [23], while the presence of a nitro group in 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone the reaction with 2,3,3-trimethylindolenine leads to an o-quinone ring

• reactions of 2-methylquinolines with 3,5-di-(tert-butyl)-1,2-benzoquinone [1] and benzophenones with o-chloranil [15]. The norcaradiene derivatives 5, formed in the next step by the intramolecular cyclization reaction of 4, undergo thermal isomerization into 2,3-dihydrotropolones 6. The formation of 2

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• yields. The single crystal structure of the compound 6e was determined by X-ray diffraction (Figure 3). The similar reaction of more nucleophilic tri(tert-butyl)phosphine and MBH carbonate of isatin resulted in a mixture of products. After carefully screening the reaction conditions, we found that DABCO

• successfully promoted reaction of tri(tert-butyl)phosphine and MBH carbonates of isatins in toluene at 80 °C for three hours. These conditions resulted in mixtures of conjugated triene cis/trans-isomers 7a–d and 8a–d with nearly 4:1 ratios (Table 2). It should be pointed out that similar conjugated trienes

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• well-structured absorption peaks clearly showing the vibronic progressions. BPP-OiPr 3 also exhibited a small peak located at 442 nm with the molar extinction coefficient (ε) of 1800 M−1 cm−1, which was similar to the previous observations of the dark S1 states for BPP 2 and its mesityl- and tert-butyl

• -butyl-substituted BPP (BPP-t-Bu, PLQY: 0.47) (Figure 2b) [21][22]. Considering that two tert-butyl groups should more effectively hinder the aggregation than one isopropyl group, we tentatively attribute the enhanced PLQY of 3 to the reduced molecular symmetry, which can relax the selection rule and

• exhibited similar emission spectra in toluene with maxima at 436 and 443 nm, respectively, with well-defined vibronic structures (Figure 2b). Notably, the absolute PLQY of BPP-OiPr 3 was measured to be 0.73, demonstrating a remarkable enhancement of the photoluminescence from BPP 2 (PLQY: 0.13) and tert

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• . For example, electron-donating groups (Me, tert-butyl, MeO, naphthyl) and electron-withdrawing groups (F, Cl, Br) attached to the benzene ring led to products 2a–i with yields ranging from 60% to 89%. Interestingly, products with strong electron-withdrawing substituents were obtained in moderate

• whether the reaction proceeded through a free radical mechanism, different free radical inhibitors were added to the reaction (reaction 7, Scheme 5). The addition of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) resulted in complete inhibition of the reaction, while BHT (2,6-di-tert-butyl-4-methylphenol

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• -fluorobenzofuran (1a) when reacted with phenylboronic acid (2a) as well as arylboronic acids containing electron-donating groups, such as a methyl group at the 3-position (2b), two methyl groups at the 2- and 5-positions (2c), and a tert-butyl group at the 4-position (2d). The reaction with 3,5

• -dimethoxyphenylboronic acid (2e), which has electron-withdrawing groups on the aromatic ring, also yielded a satisfactory result of 73%. Additionally, using 2-fluoronaphtho[2,1-b]furan (1b), the reaction with phenylboronic acid (2a) and arylboronic acids with a methyl group at the 3-position (2b) or a tert-butyl group

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• -difunctionalization of alkenes carried out with carbazates (N-aminocarbamates) and (hetero)arene nucleophiles or amines exploiting N-(tert-butyl)-N-fluoro-3,5-bis(trifluoromethyl)benzenesulfonamide (NFBS) as intermolecular hydrogen-atom-transfer reagent results in alkylarylation processes (Scheme 5) [19]. The

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