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

• benzotriazole-adduct formation proceeds poorly with sterically demanding secondary amines and fails with primary amines. However, the latter may be overcome by adding a temporary benzyl group on the amine which can be subsequently cleaved by hydrogenolysis as demonstrated by the authors. Finally, it was shown

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

• electron-withdrawing groups on the aromatic ring were well tolerated (19a–c), although substrates with strong electron-withdrawing groups, such as nitro (–NO₂), resulted in no product (19d). Additionally, alkyl, phenyl, and benzyl substituents on the nitrogen atom of N-arylacrylamides were compatible (19e

• benzyl methyl malonates (35d, 35e) and a malonate derived from (−)-borneol (35h), were all compatible with the reaction conditions, providing the final products in moderate to good yields. However, using the sterically hindered 2-fluoromalonate as a substrate led to a reduced yield of product 35f. A

• -substituted acrylamides. Compounds such as N-methyl, N-ethyl, N-isopropyl, N-phenyl, and N-benzyl-substituted acrylamides were efficiently transformed into products 37a–e under the optimized conditions. However, substrates with strong electron-withdrawing groups, such as those bearing nitro substituents (37f

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

• ; condensation; Einhorn-type acylation; 2-methyl N-benzyl benzothiazolium salts; Introduction Aroyl-S,N-ketene acetals, in particular N-benzyl derivatives 1, are very short donor–acceptor chromophores that have recently found a renaissance due to their peculiar intense solid-state emission and significant turn

• ) and electron-donating (-OMe) substituents were used. Additionally, a heterocycle could be incorporated. Different benzyl substituents were employed, and substitution at the benzothiazole core was also tolerated (Table 1). As an alternative to 1,4-dioxane, 2-methyltetrahydrofuran was tested the solvent

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• previously isolated in crystalline form in two different molecular conformations [18]. In conformer I (Figure 2, bottom), all three benzyl groups are oriented towards the interior of the macrocycle. In contrast, conformer II (Figure 2, top) features two benzyl groups projecting inward and one benzyl group

• projecting outward denoted by an asterisk. Furthermore, the resulting crystal structure reveals that 1 is also a distorted planar macrocyclic system consisting of the amino acids carbonyl oxygens facing inside the ring. All three benzyl groups are located above a single plane (more figures are provided in

• projected benzyl groups. For the 1/NaBArF24 complex, the repeating unit shows that both phenylalanine HIMs exhibit the same conformation (e.g., I) where all three benzyl groups are oriented toward the interior of the macrocycle (Supporting Information File 1, Figure S9). From the single crystal data set, we

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• reactions, have also been explored, thus boosting sustainability value. For instance, Wang and co-workers (2019) synthesized benzyl cinnamate (166) from cinnamaldehyde (162) catalyzed by an NHC catalyst (cat 4) in the presence of the low-cost oxidant CCl3CN. The reaction involves formation of acyl azolium

• and using ylide 397 altered the stereoselectivity to E-isomeric products 400 and 401 [144]. Wu and co-workers (2020) employed Pd to mediate the cross-coupling reaction of sulfoxonium ylide 402 and benzyl bromides to give the corresponding (Z)-ethyl cinnamates 403–406 in good yields via carbene

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• , probably due to the formation of a more acidic cationic gold complex. Following this annulation, reduction of the amide in 20, catalytic hydrogenation of the alkene and the N-benzyl group, and subsequent nitrogen acylation yielded chloride 21 in a 42% total yield, setting the stage for the Witkop

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• hydrogenation of the C=C double bond in the side chain gave brevicarine (2). The first total synthesis of brevicarine is shown in Scheme 3 [2][20][21]. Condensation of indole (11) with 1-methylpiperidone (12) gave compound 13 [22]. N-Alkylation of 13 with benzyl bromide, followed by treatment of the quaternary

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• alkene side product, presumably arising from mesylate elimination (Table 4, entry 4). In general, the functional group tolerance of the reaction was good, and aryl halogens, aryl CF3 moieties, and benzyl ethers were fully compatible (Table 4, entries 7 and 8). Where applicable, stereoarrays could be

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• reorganization likely involves the cleavage and re-formation of the dynamic Ctriazine–OAr bonds, and the presence of an excess of base could facilitate the formation of the thermodynamic-favored reorganized products [29][31]. The benzyl groups were subsequently removed under Pd/C and H2 conditions to afford the

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• efficiently constructed α-all-carbon quaternary centers on β,γ-unsaturated nitriles with excellent >98% regioselectivity and >98% (E)-selectivity. 1,1-Disubstituted allenes bearing silyl ether- and benzyl ether-tethered propyl groups were successfully converted into the desired nitriles 3a–c in yields ranging

• regioselectivity (>98%). Functional groups such as silyl ether, benzyl ether, and chloro moieties on allenes 4d–f were well tolerated under the reaction conditions, producing nitrile-substituted tertiary carbon products 5d–f in yields ranging from 73% to 85%. Moreover, aryl-substituted allene 4g was efficiently

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• mimics that of 2-benzyl-2,3-dihydrobenzofuran (overlaid in Figure 4), a structural motif that is commonly found within bioactive natural products. Having seen that the conformations of multivicinal fluoroalkanes can be altered by changing the stereochemistry, it follows that other physical properties can

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• 13a,d,e in 71–83% yield (Scheme 4). Carboxylic acid 13a could be reacted with glycine benzyl ester in the presence of HATU and Et3N to form dipeptide 16 (66%). In contrast, N-unprotected 2-aminoprolines are unstable and could not be isolated. Thus, the cleavage of the N-Cbz protecting group in 6b

• ester moiety with LiBH4. In the meantime, the hydrogenolysis of the benzyl ester in dipeptide 16 proceeded smoothly and afforded carboxylic acid 17 in 81% yield (Scheme 4) [16]. Conclusion In summary, the developed electrochemical decarboxylative amidation of readily accessible malonic acid monoesters

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• product 35b was obtained, confirming that the dihaloalkane compound is the source of the methylene unit (Scheme 28c). Depending on the stability of the leaving carbocation, the selectivity of the R–N cleavage follows the decreasing order for the R groups: H, t-Bu, allyl, benzyl > methyl > primary

• amine with two methyl groups and a benzyl or allyl group, the cleavage of the N–CH2Ph and N–allyl bond takes place more selective (by 85% and 67%, respectively), instead of the cleavage of an N–Me bond. This explains the high selectivity observed for some examples in Scheme 27. Finally, this methodology

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• olefins with a wide range of nucleophiles, with many organocatalyzed asymmetric examples highlighted in the literature [23][24]. We have observed that the enantioenriched 1,5-dicarbonyl Michael adducts, synthesized via organocatalyzed reaction of cinnamaldehyde with benzyl phenyl ketone, undergo

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• triad (red) was hoped to activate the benzyl alcohol nucleophile, but it does not activate (polarize) the electrophile (substrate ester group). (B) One of Rebek’s “clefts” [108][109]. The rigidly organized carboxylic acids both bind the substrate and the transition state for hydrolysis of an acetal. (A

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

• the presence of Pd-C. This deprotection protocol also facilitates an orthogonal deprotection strategy in multistep oligosaccharide syntheses in the presence of benzyl (OBn) groups (Scheme 6). The benzyl and cyanopivaloyl-protected hexarhamnoside derivative 37 was completely deprotected by a single

• -2 position to obtain 1,2-trans glycosides showing orthogonal deprotection according to the need of the compound. They introduced (2-benzyloxyphenyl)acetyl (BnPAc, 43) as a versatile leaving group showing orthogonality to both acetyl and benzyl protecting groups [127]. This group, when placed in the

• of a mixture of 1,2-cis and 1,2-trans glycosides. In this respect ether-type non-participating protecting groups like benzyl (OBn), p-methoxybenzyl (OMBn), and allyl (OAll) are implemented as the temporary protection in the C-2 position in order to obtain 1,2-cis glycoside products. Moreover, the

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• to inhibit p38α MAPK and 0.5 µM for TNF-α [10]. Pyrazolobenzothiazines containing a triazole moiety have also been studied as potential antibacterial drugs [7]. Other applications of N-substituted benzyl/phenyl acetamide pyrazolobenzothiazines include superoxide anion and DPPH radical scavenging

• . Yellow-colored precipitates of product 5 were formed which were separated via filtration followed by washing with excess of water. After drying, recrystallization was done with ethanol. Mp 265–266 °C; yield: 221 mg (88%). Synthesis of pyrazolo-1,2-benzothiazine-N-aryl/benzyl/cyclohexylacetamides 7a–h

• Dried acetonitrile (10 mL) was used to prepare a solution of compound 5 (251 mg, 1.0 mmol) followed by addition of anhydrous K2CO3 (173 mg, 1.25 mmol) under continuous stirring and heating. After 30 minutes, the solution of the respective 2-chloro-N-aryl/benzyl/cyclohexylacetamide 6a–h (1 mmol) in dry

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

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

• reaction was also fruitful to obtain 1,2-dihydroisoquinolines 25 starting from 2-alkynylbenzaldehydes, primary amines and allylic or benzyl bromide, in the presence of zinc and using the combination of Mg(ClO4)2/Cu(OTf)2 as catalyst. The use of a mixture THF/DCE 1:20 as solvent was mandatory, because THF

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

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• across various applications. In this study, we present a comprehensive methodology for synthesizing, self-assembling, and transforming polysarcosine-poly(benzyl glutamate) block copolymers, resulting in the formation of bowl-shaped vesicles, disks, and stomatocytes. Under ambient conditions, the shape

• broadening their potential applications in drug delivery and nanotechnology. Our findings shed light on the unique capabilities of polysarcosine-based polymers, paving the way for further exploration and harnessing of their distinctive properties in biomedical research. Keywords: biodegradable; poly(benzyl

• functionalities of naturally occurring amino acids, synthetic polypeptides offer a robust platform for designing drug delivery systems that meet the criteria of biodegradability and biocompatibility [13]. The present study focuses on a polysarcosine and poly-ʟ-(benzyl glutamate) block copolymer (PSar-PBLG), as it

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• ), and appetite suppressants (e.g., phentermine) [6]. Phenethylamines can be produced via numerous different procedures [7]. One of the oldest methods involves the reduction of benzyl cyanide with H2 in liquid ammonia with Raney-Nickel catalyst at 130 °C, and high pressure [8]. Another known method is

• ); 13C NMR (151 MHz, D2O) δ 122.41, 124.77, 129.01, 133.06; ESI-MS m/z: [M + 1]+ 171.0; found, 171.1; mp 190–191 °C. Benzyl alcohol (9b): The product formation was monitored by TLC using Hex/EtOAc (6:1). Once cooled to room temperature, the mixture was acidified with 20% HCl solution and extracted with

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

• primary amine-containing HIRs, or it might be due to the inability of the benzyl moiety to stabilize the sulfenate ion during the reaction. For tert-butyl 3-(p-tolylsulfinyl)propanoate (4a), and similarly to the outcome obtained for BBX 2a, sulfonamides 5ab and 5ac were obtained with moderate yields. The

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• in moderate yields (42–60%), high diastereoselectivities and good enantioselectivities (68–88% ee) (Scheme 6). The authors also attempted the reaction using N-benzyl-protected 3-chlorooxindole as a substrate. However, in this case, no reaction was observed, which indicated that the N–H group of the 3

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• benzyl azide and triethylgermanyl acetylene (see Supporting Information File 1). The most effective conditions were found to be based on the classical combination of CuSO4/NaAsc, with optimisation (see Supporting Information File 1) delivering the general conditions shown in Scheme 2. These afforded a

• and the starting material could be recovered in each case, consistent with observations by Lam and MacMillan [71][72]. Variation of the steric and electronic parameters of the germanyl acetylene was straightforward (14–17; Scheme 2b). Several limitations were observed (Scheme 2d): benzyl azides