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

• insertion [74] with ketone 91 and deprotection of the dithiane group delivered alleneketone 92. Sequential treatment of 92 with TsNHNH2 and NaH, the trimethylenemethane (TMM) diyl-mediated cycloaddition via intermediates 93 and 94 proceeded uneventfully to form the tetracyclic product 95. Next, reductive

• observed that the early-stage application of desymmetric enantioselective reduction could efficiently provide access to enantiomerically enriched intermediates with multiple stereocenters containing an all-carbon quaternary chiral center. Taking aforementioned advantages of this strategy, the synthetic

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

• our third-generation strategy featuring the employment of benzyl ʟ-valinate as the coupling component [63], tripeptide derivative 28 was synthesized in three steps. Exposure of 28 to DMDO in acetone followed by treating the resulting intermediates with Na2SO3 produced the proposed structure of aspera

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

• chiral allenes [15] is defined as [60] (Scheme 4A), while the desymmetrizing reactions of allenes [16] (Scheme 4B) and anthracenylidene [17] (Scheme 4C) are both classified as [54]. In the cases of Scheme 3A and 3C, the reaction intermediates (i.e., the p-quinone methide and the carbopalladation

• biphenyl ether backbone (H vs Me, highlighted in grey), which is reflected by the relatively large values of the index [74]. Although we intend to avoid reaction intermediates in the assignment of the stereocontrol connectivity index, we recognize the limitations in cases that chemical bonds are cleaved

• and restored in the course of the transformations (e.g., Scheme 4A and 4C). Such limitations become obvious in the cases of multistep, multi-intermediate reactions [32][33], particularly in the case of helical chirality where chirality transfer of intermediates is common [34][35][36][37][38][39]. In

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

• stabilized allyl cation intermediates that undergo regioselective trapping by internal O- and N-nucleophiles furnishing functionalized heterocycles. This method provides access to tetrahydrofuran or pyrrolidine frameworks, each bearing a trifunctionalized (E)-configured vinyl side chain. The use of a shorter

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

• offer many synthetic advantages while the wide availability of chiral NHCs can also allow for high levels of enantioselectivity. As effective enamine and active ester derivatives, Breslow and acylazolium intermediates A and B typically react via classical two-electron polar mechanisms, however, recent

• research has demonstrated that NHCs are also capable of stabilizing radical or excited-state species [12][13]. In 2020, our group reported the concept of photo-NHC catalysis where direct excitation of acylazolium intermediates generated from o-toluoyl fluoride substrates with UV-A light resulted in a novel

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• optically pure intermediates in total synthesis. This section focuses on applications of lipase-catalyzed acylation of prochiral 1,3-diols in total synthesis. Porcine pancreatic lipase (PPL) PPL, a commercially available lipase isolated from fresh porcine pancreas [26], is one of the most widely used

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• , phosphine oxides, and bisphosphonates, allows for tailored modifications that enhance selectivity, bioavailability, and reduce potential side effects [8][9][10][11][12][13]. This versatility makes them valuable not only as drugs but also as intermediates in synthetic organic chemistry, facilitating access

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• . This trend suggests that the lipophilic surfaces may destabilize hydrophilic intermediates, promoting faster conversion of HPMM to BMN, similar to the ground-state destabilization of polar substrates observed in enzymes with lipophilic pockets [54][55]. It should be noted that this result is in

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• styrene, leading to the in situ generation of two valuable intermediates that act as dual synthons for the synthesis of 2,4- and 4-substituted quinolines. As part of our ongoing efforts to develop innovative C–C and C–H activation strategies for constructing nitrogen-containing heterocycles [55][56], we

• herein report the first example of the earth-abundant iron-catalyzed oxidative cleavage of C(sp2)–C(sp2) bonds of styrenes and further utilization of the intermediates as dual synthons for the synthesis of two essential quinoline moieties as shown in Scheme 1b. Results and Discussion To validate our

• corresponding imines I and I′, as supported by the detection of imine I during GC–MS analysis. Both imines coordinate with the Lewis acid FeIII forming intermediates II and II′ with enhanced electrophilicity, respectively. Another equivalent of styrene (2a) attacks the electrophilic carbon, leading to the

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• amino alcohols derived from furfural and ʟ- or ᴅ-valinol were subjected to Torii-type ester electrosynthesis to obtain the corresponding unsaturated esters. These served as key intermediates to prepare (S)- and (R)-enantioenriched unsaturated amides by N-Alloc deprotection which induced concomitant

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• synthetic approaches (see Figure 1e) toward BINOL macrocycles had successfully used either Williamson-type reactions or Suzuki couplings for the synthesis of intermediates. Thus, we chose to compare the use of two-fold Suzuki coupling or two-fold Williamson reaction for the synthesis of macrocycles M1. For

• (in a two-fold Suzuki coupling) or with the BINOL-derived diol Me-2 (in a two-fold Williamson reaction) gave no meaningful yields of the desired intermediates Me-36 or Me-46, respectively. For this reason, we resorted to an alternative synthesis of the BINOL-based bistosylates Me/H/iPr-36. For the

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• dramatically, and the number of nitrogen-containing compounds continuously increased. These compounds find broad applications in synthesizing energetic materials, dyes, flavorings and fragrances, pharmaceutical and pesticide intermediates, as well as specialty chemicals [2]. As delineated in Figure 1, a

• multifunctionality stemming not only from its strong proton-donating capacity but also its unique capability to stabilize reactive intermediates through preferential solvation effects. The optimal solvent choice must balance multiple factors: substrate solubility, nitrating reagent compatibility, temperature control

• nominal operating parameters (e.g., elevated temperatures approaching the decomposition threshold of nitro compounds, prolonged residence times that may promote polynitration, or extreme reagent stoichiometries that could generate unstable intermediates) while monitoring key performance indicators such as

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• ), K2CO3 (0.181 mmol, 0.125 equiv), H3PO2 (0.725 mmol, 0.5 equiv.), neat, 110 °C. Yield was determined by NMR, isolated yield in parentheses. a48 h. Reaction profile and DFT energies of intermediates and transition states. M062X functional with the basis set 6-311+G(d,p) on the model reaction between

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• comparison with previous, traditional, and time-consuming synthesis of PI-88 glycan components, the one-pot glycan assembly strategy has some advantages, including: 1) acceleration of glycan synthesis, 2) avoidance of purification of intermediates during glycosylation intervals, and 3) reduction of chemical

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

•  1) [6][7][8][9][10][11][12]. Nevertheless, partially fused macrocyclic intermediates are also important as they exhibit structural strain associated with both the polycyclic segments and the inherent strain stemming from the macrocyclic structure. For instance, cyclic chrysenylenes [13][14][15][16

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• intermediates in the synthesis of several derivatives with important applications in medicinal chemistry. Furthermore, many marketed drugs feature the enaminone structural moiety. In this context, we have developed a photoredox and nickel catalytic system to rapidly forge the enaminone scaffold from 3

• ; enaminones; nickel; photocatalysis; Introduction Enaminones are relevant intermediates in organic chemistry and the pharmaceutical industry [1][2][3][4][5][6]. These enamines have a carbonyl group conjugated to a carbon–carbon double bond, owing its great versatility in organic synthesis to its ability to

• (Figure 1). In view of the important biological roles of enaminones and their relevance as synthetic intermediates, it is not surprising that there has been a continuous focus on developing general, straightforward, and efficient strategies for their synthesis. Enaminones are usually accessed by

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• of non-concerted, step wise cycloadditions leading to mixtures of five- and seven-membered heterocyclic products (cycloadducts), and respective zwitterionic intermediates were postulated to explain the unexpected reaction pathway [11]. Due to the practically equal electronegativity of carbon and

• ,d, respectively, as the expected reactive intermediates after N2 elimination from 2c and 2d. Trapping of transient thiocarbonyl S-methanides 1 with enolizable 1-substituted 5-mercapto-1H-tetrazoles 4 Adamantanethione S-methanide (1a) is considered as a prominent representative of the ‘sulfur

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• intermediates. (c) All 8 states are accessible reversibly even at lower sample voltages, indicating that switching can be performed between any given state at a low threshold voltage. That is, all states are accessible and are remarkably stable at all sample voltages. It is concluded that the high energy

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• that bulky isonitriles effectively shield the radical or cationic centers in intermediates X1 or X2, thereby preventing multiple additions of isonitrile to give the highest yields for benzamides 2be and 2ge among the scope of isonitriles. In the final step of the reaction, the addition of a water

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• transfer. In the second protocol, the β-lactone intermediates 7 are reduced to a diol and a subsequent Williamson etherification affords the oxetanes. Since both protocols consist of two steps and give only moderate yields, the overall oxetane yield and synthetic efficiency are rather low. In 2019, Marini

• -, particularly 2-methylideneoxetanes have become valuable intermediates in oxetane chemistry as they readily undergo a variety of chemical transformations, including ring-opening reactions with nucleophiles, epoxidations, cyclopropanations and [3 + 2] cycloadditions with nitrile oxides [51][52]. In addition

• potentially reactive functional groups such as alkenes, alkynes, halides or azides. In 2023, Coote et al. developed a synthetic approach to functionalised spirocyclic oxetanes 83 by combining a Paternò–Büchi reaction with succinic anhydride opening and esterification (Scheme 22) [63]. The key intermediates 82

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• structurally diversified target molecules 65–68 under optimized reaction conditions. In these cases, the high polarity of the radical intermediates of CF3CH2OH and 4-methylbenzonitrile, combined with the poor solubility of adamantane, may explain the possible reasons behind the reaction process [91]. Amidyl

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• single-electron-transfer (SET) process, leading to the formation of hybrid alkyl–Pd radical intermediates. The optimized conditions employed cesium carbonate as the base in 1,4-dioxane, under blue LED irradiation at room temperature, affording the desired products in moderate to good yields. The

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• from in the process. For suppressing the formation of side products by self-condensation of S,N-ketene acetal intermediates the reaction temperature has to be kept as low as possible for assuring kinetic control. Therefore, in contrast to the standard protocol [5][6] (Scheme 2), reacting aroyl

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• be predicted by calculation and comparison of the relative energies of the proceeding palladacycle intermediate, as postulated in the Bell–Evans–Polanyi (BEP) principle [10][11]. Focussing on the intermediates allows for easier automation of the calculations since a minimum instead of a saddle point

• electrophilic aromatic substitution and a proton abstraction mechanism via CMD, where they calculated the relative energies of the intermediates. Using their workflow, they were able to predict correctly the regioselectivity for 18 tested substrates. The main limitation of this work is the computational cost

• module [18]. Similarly to previous works [9][14], we focus on the CMD step, the first and commonly the rate-determining step in C–H activation, and consider the prototypical Pd(OAc)2 catalyst. Using a selective approach, we calculate the relative energies of all relevant palladacycle intermediates using