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

• of Lewis acid–base bifunctional catalyst (Zr-β zeolite and K2CO3) in the Meerwein–Ponndorf–Verley reduction of a concentrated furfural solution (17.3–80.5 wt % in ethanol) combined with in situ cross-aldol condensation with acetaldehyde and crotonization. Ethanol was used as hydrogen donor for the

• Meerwein–Ponndorf–Verley reduction, while acetaldehyde is generated in situ by ethanol oxidation (Scheme 50). The equilibrium allows furfural to be simultaneously converted into furfuryl alcohol and 3-(2-furyl)acrolein in one pot through a redox reaction. The highest mass conversion rate of furfural can

• hydrolysis (Scheme 59). Furfural was employed as starting scaffold in a protocol developed to form acetals as fuel additives. The acyclic acetal is generated in situ from crude furfural with propanol in dimethyl carbonate using a nanoporous aluminosilicate material Al-13-(3.18) as catalyst, and then

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

• , protection of the resultant primary alcohol, and hydrogenation afforded ketone 65. The LaCl3·LiCl-promoted addition of 65 with Grignard reagent followed by TES protection of the resulting secondary alcohol, regioselective deprotection of the TES group and in situ oxidation provided aldehyde 66. Next, 66

• 77 and subsequent deprotection produced tertiary alcohol 78. Starting from this common intermediate, on the one hand, through successive manipulations by diazotization and in situ azide substitution, AgNO3-mediated aza-Cope/Mannich [62] reaction delivered ketone 79. Subsequently, a three-step

• operation including azide–alkene dipolar cycloaddition, irradiation of the resulting triazoline to aziridine 80 and in situ ring opening followed by deacetylation achieved the first total synthesis of (−)-hunterine A (14). On the other hand, aza-Cope/Mannich reaction of 78 produced imine intermediate 81

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

• synthesis of (–)-isochaetominine A was increased from 25.4% to 30.8% over five steps. Secondly, a new protocol featuring the use of an aged solution of K2CO3/MeOH to quench the DMDO epoxidation-triggered cascade reaction was developed, which allowed the in situ selective mono- or double epimerization at C11

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

• ) catalytic cycle [28]. However, in the case of Cu(OTf)2, the active catalytic species must be generated in situ. The highest diene 10a NMR yields (63–66%) were achieved by using 20 mol % of CuCl, 3.0 equiv of Ph2IOTf (I-2) and 1.2 equiv of 2,6-di-tert-butylpyridine (B1) in EtOAc at 70 °C (Table 1, entries 16

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

• ring was assembled via a one-pot mercuriocyclization/reductive demercuration of 153 followed by two-step diol-deprotection to access compound 154. Using trifluoromethylmethyldioxirane, which was generated in situ from trifluoroacetone, Oxone®, and disodium ethylenediaminetetraacetate dihydrate (Na2EDTA

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• significant attention in this context due to its flexibility, efficiency, and practical applicability. Since the late 1980s, many research groups have investigated the use of in situ-generated low-valent titanium [20][21][22][23][24][25] and niobium [26] reagents to promote the pinacol-type coupling of imines

• described a new electrochemical procedure to provide vicinal diamines involving the use of Sn electrodes as both anode and cathode in a divided cell, Mn(OAc)3·2H2O as additive and n-Bu4NOAc as electrolyte. Under these conditions, using aldehydes and amines as starting materials to form the imines in situ

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• an important class of compounds with significant biological activities. Spirocyclic derivatives are present in a variety of natural products. We describe here the formation of spirooxindoles using an intermolecular nitrone cycloaddition reaction. The nitrone dipole was prepared in situ by cyclisation

• of an oxime, itself prepared in situ from an aldehyde. The stereochemistry of one of the spirooxindoles was determined by single crystal X-ray diffraction studies via crystallisation using encapsulated nanodroplet crystallisation (ENaCt) protocols. The chemistry involves cascade or tandem

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

• during GC–MS analysis) and formaldehyde (2a′′) via C–C bond scission of styrene in the presence of FeIII/O2, possibly through a 1,2-addition of O2 to styrene [49][58][59][60]. This in-situ generated aldehyde species then undergoes condensation with the amine 1a, leading to the formation of the

• cleavage of styrenes, catalyzed by earth-abundant iron, followed by the in-situ utilization of the resulting cleaved synthon in a domino process to synthesize highly substituted quinoline derivatives. We have demonstrated that this process can efficiently convert readily available feedstocks, including a

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• , condensation of N-sulfonylated 1,2-diphenylethane-1,2-diamines and cyclohexane-1,2-dicarboxylic acid, and the final cyclization with the in situ generated Hendrickson reagent. Keywords: bisimidazoline; cyclohexane; cyclohexane-1,2-dicarboxylic acid; 1,2-diphenylethane-1,2-diamine; Introduction Chiral

• in the formation of cyclohexane-1,2-dicarboxamides 4 due to their poor nucleophilicity. Finally, (1S,2S)-N1,N2-bis((1R,2R)-2-(sulfonamido)-1,2-diphenylethyl)cyclohexane-1,2-dicarboxamides 4 were cyclized with the Hendrickson reagent (triphenylphosphonium anhydride triflate in situ generated from

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• coordination of the boron center with the remaining C2-OH group increases its acidity, thereby generating in situ an acidic catalyst for the activation of the glycosyl donor [62][63]. In this approach, the use of glycosyl phosphites of gluco- (35) and galacto- (38) configuration as donors, in combination with

• donors of gluco-, galacto-, and manno-configuration, using a sulfonium-type promoter generated in situ from dimethyl disulfide (Me2S2) and triflic anhydride (Tf2O) [66][70]. The use of common acid scavengers, such as DTBP (di-tert-butylmethylpyridine), was not recommended, as glycosylation reactions

• 3,4,6-tri-O-benzylated 1,2-anhydroglucose 129 using an organoboron catalyst (Scheme 11). In situ-generated tricyclic borinate complexes (formed between 1,2-glycosyl diols and diarylborinic acids) effectively promoted the glycosylation with glycosyl anhydro sugars, yielding the 1,1'-α,α-trehalose

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• same reaction mixture, in situ activation of disaccharide donor 8 and acceptor 9 using TolSCl/AgOTf reagent combination was introduced. This two-step, one-pot glycosylation gave a 42% yield of disaccharide 10, maintaining good β-stereoselectivity at the galactosyl linkage (α/β = 1:5.8). The 2

• position of the galactoside using 1.3 equivalents of bis(trimethylsilyl)amine (HMDS), concurrently leaving the 3-OH group at the non-reducing end available for glycosylation with the ᴅ-Galf donor 12 [47]. After the in situ activation with TolSCl/AgOTf, product 13 was obtained with a 76% yield and exclusive

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

• synthesis of esters of phosphonous or alkylphosphinic acids [33][34][35]. Only a single application of cesium hypophosphite was shown in the literature. CsH2PO2 was prepared in situ and used for formation C–P bond by radical addition to unsaturated carboxylic acids [36 ]To summarize the above, it is crucial

• to fundamentally study the influence of the cations in hypophosphites on this process. In this work, the hypophosphites of Li, K, Rb, and Cs were obtained in situ, the influence of alkali metal cations on the efficiency of reductive amination was assessed and the obtained results were compared with

• investigation of cation influence on the efficiency of reductive amination, a commercially available NaH2PO2, and in situ synthesized LiH2PO2, NaH2PO2, KH2PO2, RbH2PO2, and CsH2PO2 were compared. To account for the reactivity of H3PO2 as is, the reaction outcome both for the neutral XH2PO2 (where X is Li, Na, K

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• '-disubstituted ureas were initially reacted with oxalyl chloride to form imidazolidinetriones 1a,b, which were then added to an iminophosphorane formed in situ from an aryl azide and triphenylphosphine. As a result of the aza-Wittig reaction, 5-iminohydantoins 2a–i were then used as dipolarophiles in the 32CA

• carbethoxyformonitrile oxide (CEFNO) precursor. The nitrile oxides were generated in situ by the action of a base (Et3N) to compounds 4a–d in the dipolarophile-containing solution to prevent high concentrations of dipole molecules and to minimize the inevitable competition between the 32CA reaction and the isomerization

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 Lodz, Pomorska 163/165, 90-236 Łódź, Poland Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Łódź, Poland 10.3762/bjoc.21.113 Abstract The in situ-generated

• protonate this basic fragment, undergo 1,3-addition leading to corresponding products of S,S-, O,S-, or N,S-acetal type. For example, trapping of the in situ-generated adamantanethione S-methanide (1a) with tert-butylthiol or benzyl alcohol leads to the corresponding S,S-dithioacetal and O,S-thioacetal

• -established methodology, transient thiocarbonyl S-methanides 1 should be generated in situ by thermal decomposition of their precursors, i.e., spiro-1,3,4-thiadiazolines 2 [5][6]. In contrast to adamantanethione (7a), which reacts with diazomethane (CH2N2) yielding a mixture of regioisomeric 1,3,4- and 1,2,3

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

• and the resulting 1,3-acetyloxyiodides 37 were treated in situ with methanolic t-BuOK to promote the cyclisation. Best results for the oxetane formation were obtained for dimethylphenylvinylsilane, while alkenes without the silyl group afforded mainly homoallylic alcohols 39, presumably through an

• groups including esters, ketones, sulphones and heteroaryls. The mechanistic proposal, supported by DFT calculations, starts with an oxidative decarboxylation to give an aminooxetanyl radical 157. This species is in turn coupled with the aryl halide by the active Ni(0) catalyst (generated in situ by

• followed by an acid-catalysed intramolecular oxetane opening (Scheme 53) [107]. Although it is not a true domino process as the ring opening does not take place in situ, the work-up after the first step involves only a short column

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

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

• 1 suggests starting from aroyl chlorides 2 and 2-methyl-N-benzylbenzothiazolium salts 3 by a condensation transform (Scheme 1). The condensation essentially represents an addition–elimination sequence that starts with the nucleophilic S,N-ketene acetal 4, in situ generated from substrate 3 by

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

• situ formation of an active enol ester 26. The phenol was formed in situ during the second step from phenylboronic acid oxidation utilizing H2O2 (30%) as green oxidant (Scheme 8B) [40]. Sureshbabu and co-workers (2023) activated the carboxyl group of 4-hydroxycinnamic acid (1) by selectively reacting

• in situ nitro reduction using Mn powder to afford the amide intermediate 42. The acid halide once again was applied for cinnamic acid amidation. Xiao and co-workers (2021) performed a transesterification and aminolysis of the tert-butyl ester 43 simply by using PCl3 through in situ generation of the

• pentafluoropyridine (PFP) via in situ formation of an active acid fluoride 48 to afford the corresponding amides 13 and 47 in moderate yields (Scheme 15) [47]. In addition, the amidation process could be scaled up to a gram scale to give 47 in 90% yield. Maruoka and co-workers (2021) converted cinnamic esters into

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

• inconsequential due to the reversibility of hemiaminal. Consequently, further reduction of the amide could complete the total synthesis of (+)-fawcettimine with in situ adjustment of the hemiaminal configuration. The incorrect configuration observed in the Mukaiyama hydration also inspired the authors to develop

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• carbon monoxide were used as starting materials, and two natural product frameworks of phenanthridone and acridone alkaloids could be selectively obtained by controlling ligands. The reaction of o-iodoaniline with in situ-generated arynes under CO atmosphere under ligand-free conditions selectively

• utilizing in situ-generated π-allylpalladium complexes to capture strained cyclic allene intermediates (Scheme 4) [22]. By modulating the ligands in the reaction system, two distinct polycyclic scaffolds, 13 or 14, could be synthesized with high selectivity. Mechanistically, the Pd(0) catalyst coordinates

• formation of intermediate Int-87 via oxidative addition. Rapid coupling with the in situ-generated acyl radical produces copper-bound intermediate Int-88. Base-mediated anionic exchange then displaces the halide ligand with amine, yielding intermediate Int-89. Final reductive elimination from this species

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• . Access to vicinal boron scaffolds 4f and 4g provided conclusive evidence that sensitization of alkenylboronic esters is achievable using xanthone, with in situ oxidation enabling direct access to otherwise challenging to synthesize cyclobutyldiols. The lower observed diastereoselectivity may reflect

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

• for the in situ generation of hydrogen cyanide (Scheme 1a). This method achieved high regioselectivity and enantioselectivity, highlighting the potential of allene hydrocyanation for the synthesis of complex nitrile-containing products. In another approach, the Minakata group used electrophilic

• scope for the formal hydrocyanation with 1,1-disubstituted and 1,1,3-trisubstituted allenes was examined (Scheme 3). All reactions were performed in the presence of 5 mol % IPrCuCl to generate the allylaluminum reagents in situ, followed by cyanation at room temperature for 30 min. This method

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• reaction proceeded via an oxidative addition and reductive elimination processed in the presence of Ni(0), which was produced in situ from NiBr2 in the cathode. Palladium is one of the most important metals used as a catalyst in non-electrochemical reactions. In 2020, Budnikova et al. [58] reported a

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• , depending on the catalyst loading. This result underscores the importance of calcium in complex 4 for this particular transformation. We assume that the conversion of complex 4 to the active catalytic species might rely on the in situ formation of the cyanide species from the reaction between Ca complex 4

• our previous work [45], we carried out the enantioselective hydrocyanation of hydrazones using Ca–BINOL phosphate complex 6 at −10 °C in DCM for 72 h. In addition to those reaction conditions, we initially used t-BuOH as an additive [45]. The Ca–BINOL phosphate complex 6 was prepared in situ by

• hydrocyanation product with opposite chirality was obtained, in comparison to experiments with the in situ formed Ca complex (Table 2, entries 1–3). It appears that the way in which catalyst 6 is generated (pre-formed or in situ), has a major influence on enantioselectivity, while the addition of t-BuOH has