Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• strategies and creative tactics, reflecting how emerging synthetic capabilities and concepts can positively impact natural product total synthesis. Keywords: biomimetic synthesis; C–H functionalization; complanadine; lycopodium alkaloid; skeletal editing; total synthesis; transition metal catalysis

• reaction to rapidly establish the tetracyclic skeleton of complanadine A and an iridium-catalyzed site-selective pyridine C–H borylation followed by a Suzuki–Miyaura cross coupling to forge the C2–C3’ linkage. Their synthesis achieves a high degree of synergy between classic transformations and modern

• with an Ir-catalyzed regioselective C–H borylation developed simultaneously by Ishiyama, Miyaura, Hartwig, and co-workers and Smith and co-workers [26][27]. First, the triflate group of 33 was removed by a Pd-catalyzed reduction with ammonium formate as the reducing reagent. The resulting Boc-protected

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• singlet state, which undergoes intersystem crossing (ISC) to form the excited triplet state B. An intramolecular 1,5-hydrogen atom transfer (HAT) then ensues, producing the 1,4-diradical C, which can be converted into diverse products such as alkenes and enols (Scheme 1a). Notably, the 1,4-diradical

• -hydroxy-β-lactams or 2-hydroxycyclobutanones can function either as inherent structural motifs in target natural products or as strained reactive intermediates, facilitating C–H functionalization via four-membered ring opening [6][7][8][9][10][11]. Quinones display distinct photochemical reactivities

• ]. In contrast to the direct radical coupling in Norrish–Yang cyclization, the distal biradical F, formed from quinone E through a pathway analogous to that of C in the photoredox process, subsequently undergoes intramolecular SET to generate a zwitterion G. This intermediate is then trapped by the

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• accord with the depicted C2v-symmetric structures. Figure 3 shows the 1H NMR spectra recorded for G2W1–G2W4 in DMSO-d6 at 400 MHz. As expected, all four hosts display two singlets for the equatorial CH3 groups (a, b), two pairs of doublets for the diastereotopic CH2 groups (c,c’ and d,d’) in the expected

• . Before use, samples of H2, G2W1–G2W4 were repeatedly washed with water to remove TFA (monitored by 19F NMR) and activated by grinding and heating overnight at 90 °C under high vacuum. Experimentally, we incubated equimolar amounts (7.2 μmol) of each host with aqueous solutions of each dye (240 μM, 1 mL

• ) for 1 hour using a ThermoMixer™ (T = 25 °C, 800–1000 rpm). For the experiments with acridine orange (100 μM, 2.4 mL) and methylene violet (38 μM, 6.4 mL) lower concentrations were used due to solubility issues. Following incubation, the samples were centrifuged (11,000 rpm, 10 min for methylene blue

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• influenza [7], while chlorinated analogues such as 3 have demonstrated activity against hepatitis C (Figure 1) [8]. Stereoselective methods to access halogenated γ-butyrolactones are therefore valuable, as they enable access to nucleoside analogues which have applications in treating cancer and certain

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• Anna C. Renner Sagar S. Thorat Hariharaputhiran Subramanian Mukund P. Sibi Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota, 58105-5516, USA 10.3762/bjoc.21.174 Abstract This perspective is focused on enantioselective free radical reactions. It

• obviating the need for both enantiomers of the ligand. Although chiral Lewis acid-mediated radical reactions were groundbreaking, they suffered from major disadvantages: (a) high catalyst loadings (stoichiometric or sub-stoichiometric), (b) large amounts of the radical initiator, (c) the need for a large

• demonstrated to forge C(sp2)–C(sp2) as well as aliphatic C(sp3)–C(sp3) bonds. The Fu group reported a nickel-catalyzed α-alkylation of racemic secondary α-bromoamides 18 using organozinc reagents 19 (Scheme 4A) [32]. A chiral nickel complex, obtained from the mixture of chiral pyridinebisoxazoline ligand L2

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• synthetic value of this method. In 2017, the Liu group established a precise control over cyclization sequences of 1,2-diphenylacetylenes by modulating the nitrogen-substitution patterns, enabling divergent syntheses of benzo[a]carbazole and indeno[1,2-c]quinoline derivatives (Scheme 9) [16]. When the

• intermediate 40 when using substrates with unsubstituted nitrogen. Concurrent oxygen-involved cyclization then furnished indeno[1,2-c]quinoline 41 (Scheme 9, path b). This work established a pathway-controlled strategy for efficient access to benzo[a]carbazole and indeno[1,2-c]quinoline derivatives. In 2019

• )-catalyzed transformation to afford tetracyclic products 99 (Scheme 20, path c). This allenylation reaction provided efficient access to functionalized indole derivatives by regulating catalyst systems and substituent patterns. In 2010, the Iwasawa group established a stereoselective synthetic strategy

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• positioned on the opposite lobe of the protein, as compared to lysine 241 of CLK3 (N-lobe for DYRK1A vs C-lobe for CLK3), but the docking experiment showed that a 180° rotation of the benzoic acid allowed the inhibitor to interact with lysine 175. In addition to molecular simulations, this salt bridge is

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• absolute configuration of scarce natural products, including heptavalinamide A [11] and poecillastrin C [12][13] by a combination of chemical degradation, chemical synthesis, and liquid chromatography–mass spectrometry (LC–MS) analysis. The 3-methylpent-4-en-2-ol (MPO) moiety is commonly found at the

• chiral HPLC columns and with various elution profiles, the four stereoisomers of 6 were successfully separated on a CHIRALPAK ID-3 column at 40 °C with aqueous MeOH gradient elution (Figure S3, Supporting Information File 1). The developed method for absolute configuration assignment of MPO was applied

• natural 1, showed a retention time identical to that of (2R,3S)-11 (Figure 2b), thus assigning the absolute configuration of the MPO moiety in 1 as (10R,11R) [29]. This assignment was consistent with prior reports, and the observed specific rotation of 1, measured as [α]D26 +12 (c 0.1, MeOH) closely

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• regioselectivity issues, multistep procedures, and limited applicability to tetra-ortho-substituted structures. Herein, we describe a direct, one-pot Pd-catalyzed dehydrogenative C–N coupling between aryl bromides and arylhydrazines to access non-symmetric azobenzenes. The use of bulky phosphine ligands and

• intricate and inefficient using these standard synthetic protocols. The transition-metal-catalyzed C–N bond formation has emerged as a viable route to access non-symmetric azobenzenes, owing to the broad functional group tolerance of Buchwald–Hartwig amination reactions [34][35][36][37][38][39][40]. Kong

• hydrazines. Their method involved a three-step process comprising Cu and Pd-catalyzed C–N bond formations followed by a dehydrogenative deprotection step (Figure 1b, top) [42]. This desymmetric approach was further employed by Oestreich and co-workers in 2022, who introduced silicon-masked diazenyl anions in

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• 1,1-dioxide structural element. Results and Discussion We synthesized target compounds 3 exhibiting new tricyclic (3a–c, 3f–h, Scheme 1, Table 1) and tetracyclic (3d,e,i,j) ring systems starting from 8-chloro-2,4-dimethyl-2H-1,2,3-benzothiadiazine 1,1-dioxide (4a) and 8-chloro-2-methyl-4-phenyl-2H

• were previously used for the synthesis of 7-nitroindole derivatives: heating in polyphosphoric acid (PPA) at 80 °C [24][25]. However, our attempt was not successful. Experiments with zinc chloride, the most commonly used Lewis acid catalyst in Fischer indole syntheses, also failed under various

• performed using the method described in the literature [18], i.e., by heating compounds 5a,b with ketones 6a–e in the presence of bismuth nitrate pentahydrate catalyst and PPA in methanol at 110 °C in a closed vial (Scheme 1, method B). In the synthesis of asymmetric hydrazones 7a,c,f,h, the major product

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• conjugates (S)-2a–e in CH3CN. The UV and CD spectra of the previously reported conjugates were measured in various polar and non-polar solvents, but the intensities and shapes were almost unchanged [41]. The conjugates (S)-2a–e are composed of two methoxy-biphenyl chromophores connected with a C–C single

• derivatives [41] the preferred conformation of (S)-2a can be proposed (Figure 2). In the case of the P conformer, a Newman projection along the C–N bond reveals that the bulkier substituent, the hydroxymethyl group (denoted as L), is close to a seven-membered ring, and is destabilized by steric repulsion with

• of all local minima employing DFT at the B3LYP/6-31G* level of theory [47]. Four low-energy conformers of (S)-3a were identified within 10.0 kJ/mol (Figure 3). Among them, conformers A and D exhibited an M twist between the long axes of the biphenyl chromophores, whereas conformers B and C displayed

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• ), tert-butyl isocyanide (3a), and TMSN3 (4) in 2 mL of MeOH. After heating the reaction mixture at 40 °C for 12 h, the solvent was removed and changed to 2 mL of MeCN followed by heating at 130 °C for 2 h (Scheme 3A). However, no desired product was detected in the reaction mixture. The functional groups

• introduce reactants in a sequential manner. Thus, we changed the reaction conditions by first reacting 0.2 mmol each of 1a and 2a in 2 mL MeOH at 40 °C for 40 min to form the Schiff base Int-I followed by the addition of 0.2 mmol each of 3a and TMSN3 (4) to obtain the desired 1,5-DS-T 5a as Ugi–azide adduct

• . After evaporation of the solvent MeOH, the residue was redissolved in 2 mL of MeCN and heated at 130 °C for 2 h in a sealed vial to give product 7a in 90% yield after purification via Cu-free intramolecular click reaction (Scheme 3C) [46]. This Cu-free intramolecular cyclization provides key practical

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• Lifen Peng Ting Wang Zhiwen Yuan Bin Li Zilong Tang Xirong Liu Hui Li Guofang Jiang Chunling Zeng Henry N. C. Wong Xiao-Shui Peng Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of

• -involved ureas, annulation of o-arylalkynylanilines, cyclization of 2-ethynylanilines, selenocyclization of diselenides with 2-ethynylanilines as well as C–H indolization of 2-alkynylanilines with 3-functionalized indoles. Isoindolones were synthesized successfully by electrochemical annulation of

• used as an inhibitor of cyclin dependent kinase (CDK8) [31]. Sulfonamide-N-benzoxaborole analog GSK8175 is an inhibitor against hepatitis C virus (HCV) [20] (Figure 1). The construction of five-membered rings obtained growing attention [32][33][34][35][36][37][38], and alkynes [39][40][41][42][43][44

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• catalysts including Ni/CeO2-γAl2O3, spinal NiAl2O4 and Ni/La2O3-αAl2O3, at 230 °C and 3.2 MPa. Using a chiral catalyst composed of [RuCl2(benzene)]2 and SunPhos, an effective asymmetric hydrogenation of α-hydroxy ketones was reported, yielding chiral terminal 1,2-diols in up to 99% ee. This Ru-catalyzed

• -proline as a catalyst (Scheme 25) [100]. The C–C-bond formation between biomass-based feedstock by aldol condensation reactions of furfural with 1-hydroxyacetone has been reported by Subrahmanyam and co-workers (Scheme 26) [101]. C4 biobased carbonyl platforms Acetoin Acetoin is a very important C4

• HFO with benzoic acid amide or furan-2-carboxamide in 1:1 molar ratio at 70 °C for 4–8 h (Scheme 42, path c) [132]. The reaction of HFO with 2-methylfuran in a 1:2.2 molar ratio in diethyl ether solution at room temperature in the presence of catalytic amounts of perchloric acid for 5 hours led to the

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• , (−)-glaucopine C, and (+)-allocyathin B2 The cyrneine diterpenoids represent an important subfamily of cyathane diterpenoids which possess a common 5-6-7 fused tricarbocyclic core with two all-carbon quaternary stereocenters. Many impressive syntheses have been reported to date [18][19][20][21][22][23][24][25

• ][26][27][28][29][30]. In 2018, the group of Han accomplished the total synthesis of (+)-cyrneine A (7), (−)-cyrneine B (9), (−)-glaucopine C (10), and (+)-allocyathin B2 (8) by a collective manner [31]. In their synthetic route, an enzyme-catalyzed desymmetric enantioselective reduction of 1,3

• (9). Secondly, a based-mediated concomitant double bond migration and deacetylation, and selective oxidation of allylic primary alcohol accomplished the total synthesis of (−)-glaucopine C (10). On the other hand, Barton–McCombie deoxygenation and isopropylation of 43 produced ketone 52. Subsequently

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• . The former was demonstrated by the synthesis of alkaloid 14-epi-isochaetominine C that was used to determine the enantiomeric excess of the synthesized natural product (98.7% ee), while the latter was illustrated by the synthesis of both enantiomers of the alkaloid isochaetominine. Additionally, the

• reported structures of alkaloids aspera chaetominines A and B have been synthesized. Moreover, the four-step synthesis of the reported structure of aspera chaetominine B generated another diastereomer that was converted in one-pot to (–)-isochaetominine C, which turned out to be the revised structure of

• Aspergillus nidulans [24]; 3) (–)-isochaetominines A−C (4 - 6) and (+)-14-epi-isochaetominine C (7), isolated from the solid-substrate culture of an Aspergillus sp. Fungus [25], and from other sources for (–)-isochaetominine C (6) [26][27][28][29]; 4) isochaetominine (8) from Aspergillus fumigatus, an

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• Street, Moscow 11991, Russia 10.3762/bjoc.21.161 Abstract Indolo[1,2-c]quinazoline derivatives have emerged as promising chemotype in drug discovery due to their versatile biological activities, including antimicrobial and antiviral properties. In this study, we report the design, synthesis, and

• biological evaluation of novel indolo[1,2-c]quinazoline derivatives, with a particular focus on their antiproliferative potential against human cancer cells. We introduced structural modifications at positions 5, 6, and 12 of the indolo[1,2-c]quinazoline core to explore the structure–activity relationships

• polycyclic structures, DNA was not the primary target for their antiproliferative effects, as confirmed by FID assay and fluorescence titration studies. This study represents the first comprehensive evaluation of indolo[1,2-c]quinazolines as potential scaffold for the development of antitumor agents

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• reported. A bioinspired approach represents many advantages to bring benefits to total synthesis. It could rapidly achieve complexity of the target molecule from a much simpler precursor in diverse forms of transformations such as cascade reaction, cycloaddition, and C–H functionalization, thereby, shorten

• propose the biosynthetic pathway, which has not yet been reported in Duh’s isolation report (Scheme 1a). In our proposal, the linear sesquiterpenoid trans-nerolidol (1) with a chiral tertiary alcohol undergoes dihydroxylation to generate triol 2, which further proceeds a C–C bond cleavage to afford

• evidences of chemical transformations. Thus, a bioinspired total synthesis was investigated (Scheme 1b). Synthetically, we did not start from trans-nerolidol (1) to construct a C–C bond cleavage. Instead, a convergent coupling approach was selected to quickly access the aldehyde precursor. Phenyl sulfide 5

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• light-harvesting carbazole units with photoresponsive azobenzene units in a unique macromolecular architecture (Figure 4c) [48]. The resulting cross-linked polycarbazole structure led to a high solar thermal storage capacity of 179.9 J/g and an extended half-life at 60 °C, increasing from 7 min for the

• azobenzene small molecules into polymer fibers [65], enabling solvent-free charging and discharging under visible light (Figure 6a). This material exhibited good capacity for releasing high-temperature heat (80–95 °C) at room temperature and in cold environments, along with an energy storage lifetime

• charged solar thermal fuels for deicing tests [74], showing effective ice removal capability under green light irradiation (Figure 7a). Wang et al. developed a photostimulated self-heating wristband [94] that elevates surface temperature from 29 °C to 44 °C upon blue light irradiation, protecting users

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• at reflux in acetic acid for 3 h for aminotriazole 1a or in n-BuOH for 7 h in case of aminotriazole 1b led to the formation of oxygen-bridged 2-(methylthio or methoxy)-11,12-dihydro-5H-5,11-methanobenzo[g][1,2,4]triazolo[1,5-c][1,3,5]oxadiazocine-5-carboxylic acids 4a–j (Scheme 2, Table 1). It should

• trace amounts of Schiff bases between amino-1,2,4-triazole and salicylaldehyde as well as with impurities of the reagents. This is most likely due to the electron-withdrawing nature of the substituent at C(3) in these 5-amino-1,2,4-triazoles that do not favor the proceeding of the MCR in contrast to 5

• -aminotriazoles 1a,b having pronounced electron-donating substituents (methylthio- and methoxy groups). On the other hand, the MCR of the reagents 1a, 2a–c and 3 under ultrasonic irradiation for 2 h at room temperature (25 °C) (Scheme 3) afforded a mixture of 5-(2-hydroxyphenyl)-2-(methylthio)-7-((3-(methylthio

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• -ketoglutaric acid in the four-component Ugi reaction with equimolar amounts of the reagents. It was found that stirring of aromatic aldehydes 2a–d, aromatic amines 3a–d, KGA (1) and tert-butyl isocyanide (4) (in a 1:1:1:1 molar ratio) in methanol for 24 hours at 45 °C resulted in the formation of 5-((aryl)(1

• isocyanide (4) in a molar ratio of 1:2:2:2 in MeOH and subsequent stirring at a temperature of 45 °C for 24 hours led to the formation of N1,N5-bis(2-(tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)-N1,N5-bis(4-chlorophenyl)-2-oxopentanediamide (6a) in 55% yield (Scheme 2, pathway B; Table 2). Compounds 5

• contain a free carboxyl group and thus can also be used as an acidic component in the Ugi reaction. Indeed, it was established that the reaction of 5-((2-(tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)(4-chlorophenyl)amino)-4,5-dioxopentanoic acid (5a) with aldehydes 2a,c, amines 3a–c, and tert-butyl

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• calculations have provided valuable insights into the photochemical stereoselectivities of cyclic azoalkenes. In 1998, Yamamoto and co-workers investigated the reaction paths for α-C–N and β-C–C bond cleavage during the direct and sensitized photolysis of DBH [81]. The minimum energy geometries in S0, S1, T1

• , and T2, conical intersections, transition structures, and singlet–triplet crossing were computed using CASSCF(10,8)/6-31G(d)//MP2/6-31G(d) [81]. The results suggested a stepwise C–N bond breaking with the formation of the diazenyl diradical intermediate [81]. In 2003, Olivucci and his co-workers

• inverted housane [83]. Chen and Li explored the potential energy surfaces and surface crossing points of 2,3-diazabicyclo[2.1.1]hex-2-ene with CASPT2(12,10)/6-31G(d)//CASSCF(12,10)/6-31G(d,p) in 2006 and concluded that on the S1 surface one C–N bond is broken [84]. In 2011, Abe and co-workers investigated

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• molecule is characterized by the absence of mirror planes and centers of inversion. Central chirality arises when four distinct substituents (a, b, c, and d) are arranged tetrahedrally around a central atom (Scheme 1A). Non-central chirality – such as axial and planar chirality – are becoming increasingly

• can be generated from achiral starting substrates by various means that assemble the four distinct substituents (a, b, c, and d) (Scheme 1D). In the case of central chirality, the differentiating substituents are often directly attached to the newly formed stereocenter. By contrast, for non-central

• chirality, the pairs of substituents (a and b, c and d) are separated in space because the stereogenic scaffolds span multiple atoms. Consequently, bond cleavage and formation occur at positions that are distant from the stereogenic elements and remote from the actual points of differentiation among the

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• [14]. Interestingly, this also works for terminal alkynes, which are typically known to undergo direct C(sp)–H arylation instead [15][16]. In the context of 1,2-carbofunctionalization, terminal alkynes are more scarcely studied. Among those few examples is a trifluoromethylative thiocyclization

• on intermediate allyl cation (Scheme 1C). The obtained tetrahydrofuran and pyrrolidine derivatives with highly substituted vinyl side-chains are regarded as privileged structures in medical chemistry [23][24]. Moreover, the resulting styryl functionality (Ph-C=C-) is often found in drug molecules as

• )dimethylsilane (7a) – and analogous aliphatic chain-containing propargylsilanes 7b,c were obtained from the commercial hept-1-yne [26]. While searching for appropriate arylation conditions (Table 1, entry 1) we observed the formation of both the arylated diene 10a and silylindene 11a (≈75:25). Both products are

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• catalytic photoenolization/Diels–Alder (PEDA) reaction [14][15]. In this process, the NHC fragment present in the acylazolium species influences the absorption wavelength and fundamental photochemical reactivity of the C=O bond, enabling a “ketone-like” photoreaction from otherwise unsuitable carboxylic

• species C benefitting from additional stabilization by virtue of electron delocalization onto the NHC-derived azolium ring [17][18][19][20]. Similarly, the cationic azolium fragment in acylazolium salts can effectively lower the carbonyl reduction potential relative to the starting material with single

• -electron reduction delivering the same stabilized radical C. Beginning with a seminal report by di Rocco and Rovis in 2012 [21], the combination of NHC and photoredox catalysis has recently been the subject of intense research activity [22][23][24][25][26][27][28][29][30]. Employing the latter reductive