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

• case of aldehyde 2b, the MCR always led to the formation of a mixture of products 5d and 6d. Attempts to synthesize 5d and 6d as individual compounds under various conditions were unsuccessful. In addition, it was found that compounds 5 can be converted into oxygen-bridged heterocycles 4 after 1 hour

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

• additional photocatalyst. Moreover, under the same photocatalyst-free conditions, UV-A-light-mediated reduction could be achieved using triethylsilane as the only reductant with subsequent desilylation and NHC elimination with fluoride delivering the corresponding aldehyde product. Keywords: carbenes

• transformations of carbonyl substrates with umpolung processes of aldehydes such as the benzoin condensation and Stetter reaction being particularly well studied [4][5][6][7][8][9][10][11]. In these processes, addition of the NHC to the aldehyde followed by proton transfer generates the enamine-like Breslow

• yield (Scheme 3c). The successful generation of the aldehyde from the azolium species derived from the corresponding carboxylic acid highlights the potential of this two-step sequence as a method for the partial reduction of carboxyl compounds. Such transformations can be challenging in organic

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• was initially investigated (Scheme 3). Chan’s diene (16) was subjected to condensation with freshly distilled aldehyde 17 in THF at room temperature, using a catalytic system comprising Ti(OiPr)4/(S)-BINOL complex (2.0 mol %). Subsequent deprotection with pyridinium p-toluenesulfonate (PPTS) at 0 °C

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

• Lewis acid-mediated semi-pinacol rearrangement, this work involved a CRL-catalyzed desymmetrization of prochiral diol 51 (prepared from aldehyde 50 in four steps), providing monoester 53 in 57% yield with 83% ee. Notably, 1-ethoxyvinyl 2-furoate (52) was selected as the acyl donor in this step to

• the cyclohexanone ring into 120, and the resulting hydroxy group was protected to give ketone 121. The γ-lactam moiety of compound 122 was then constructed in subsequent 12 steps. SmI2-mediated intermolecular Reformatsky-type reaction with aldehyde 123 yielded compound 124. Finally, salinosporamide A

• ) and the following acid-mediated cyclization formed another tetrahydrofuran ring. The resulting compound was then converted into lactone 174 via 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)-mediated oxidation. Lactone 174 was then converted into aldehyde 175 in three steps, which underwent Horner

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

• 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

• the presence of a Lewis acid. The use of BF3·OEt2 gave a low yield of the desired alcohol 2 [29]. This was improved slightly with Sc(OTf)3 as the Lewis acid, which could be used substoichiometrically [30]. The alcohol 2 was converted to the tosylate 3 and subsequent ozonolysis gave the aldehyde 4. The

• aldehyde 4 could now be tested in the cascade chemistry. This entails the addition of hydroxylamine to form the oxime, followed by cyclisation (with displacement of the tosylate) to give the nitrone for the desired dipolar cycloaddition reaction. Related chemistry (without the oxindole) with a halide

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• directly used as a planarly chiral primary amine catalyst in the asymmetric electrophilic amination reaction of aldehyde 34, which yielded the α-amination product 35 with high enantioselectivity. In 2022, our group disclosed an enantioselective macrocyclization protocol for the asymmetric synthesis of

• organocatalyst in the asymmetric amination of aldehyde 34, whereas inherently chiral aniline N-oxide 59 showed promise in the chiral recognition of mandelic acid. In 2024, Tong, Wang and co-workers disclosed an efficient method for synthesizing inherently chiral heterocalix[4]arenes through an asymmetric

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

• -triazoles 28 can be obtained by click chemistry (Scheme 6B) via one-pot deprotection of 26 and Cu(I)-catalysed reaction with an azide [43][44]. Heteroarylimines 31a,b can be easily obtained by condensation of a (hetero)aromatic aldehyde 30a,b with a (hetero)aromatic amine 29a,b [36][37][38] (Scheme 7). The

• choice of aldehyde and amine will determine the direction of the imine bond and the geometry of the Z-isomer. Examples Non-ionic bithienylpyrrole push–pull azo dye 32 was successfully introduced in liquid-crystalline matrices with thermal relaxation in the µs order, making them among the fastest liquid

• aldehyde and, if required, N-functionalisation via nucleophilic substitution (for aliphatic substituents) or palladium-catalysed cross-coupling (for aromatic substituents) (Scheme 25) [77]. Hemithioindigo can be synthesised by treating phenylthioacetic acid (83) with triflic acid. Then, the product is

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

• 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

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

• the DFT calculations (Scheme 5, Figure 2). Firstly, reductive amination of an aldehyde started from a nucleophilic addition of the amine to the carbonyl group of the aldehyde. In the presence of acid, this step could occur via acidic catalysis involving a protonation step of an amine (Step_2) or

• protonation of an aldehyde (Step_2’). Due to the higher basicity of the secondary amine compared with the carbonyl group of benzaldehyde, protonation of dimethylamine was the main reaction pathway (30.9 vs −2.6 kcal/mol). However, it was found that the protonation of the carbonyl group led to a great

• absence of an external hydrogen source. The alternative pathway to form a hemiaminal could not include the interaction of an acid with amine or aldehyde, nevertheless, the non-catalytic path had ΔEa = 32.1 kcal/mol (TS2→3'') which meant that hemiaminal definitely emerged faster via the amine protonation

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• condensation between 27 and the aldehyde afforded INT-A, which was activated by the CPA catalyst through hydrogen bonding interaction. The nucleophilic addition of isocyanide to Int-A produced INT-B bearing a stereogenic center. Subsequently, INT-B underwent intramolecular cyclization to generate axially

• bearing both C–C axial and central chirality (Scheme 9c) [57]. Key to this work relies on the implementation of an efficient Ag2O/L7-catalyzed desymmetric [3 + 2] cycloaddition of prochiral biaryl dialdehydes 62 with α-substituted α-acidic isocyanides. We have also demonstrated that the retained aldehyde

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• group in compound 10. Compound 10 can be realized by introducing an ester group in 9, which is the [3 + 2 + 1] cycloadduct from 8 and CO using a Rh catalyst. The [3 + 2 + 1] substrate of yne-vinylcyclopropane (yne-VCP) 8 can be synthesized by Wittig reaction from cyclopropyl aldehyde 7, in which the

• carbonyl group, giving 7 in 59% yield. Then, under basic conditions, the aldehyde group in 7 was converted into a vinyl group via Wittig reaction, affording yne-VCP substrate 8 in 90% yield. During this process, the TMS protecting group was lost. We then investigated the [3 + 2 + 1] reaction of 8 and CO

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• similar behavior was observed in the analogous aldehyde counterpart (cis-pent-2-en-4-ynal) whose cyclization proceeds with a lower barrier than the parent system (ΔE≠ = 30.3 kcal/mol) although the corresponding transition state is also non-aromatic (NICS(3, +1) = −1.5 ppm. Therefore, we found once again

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• under the Vilsmeier–Haack reaction conditions provided aldehyde 8 in high yield. To further assess the scope and limitations of the developed annulation protocol, we investigated the reactivity of aza-analogs of ester 1, indoles 9a‒c, toward azirine 2a under the same conditions. The reaction of N

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• thioamides 1h,i,k,n,o,s,t,v,w,y,z (general procedure). A mixture of the corresponding thioacetamide (1.0 equiv), aldehyde (1.1–4.0 equiv) and DBU (0.1 equiv or 1.0 equiv for 1h,o) in ethanol was stirred for 2–23 h at room temperature. For thioamide 1i, the reaction time was 96 h at 80 °C. The formed

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

• of oxetanes from epoxides using sulphur-stabilised carbanions such as dimethyloxosulphonium methilide (105) or S-methyl-S-(sodiomethyl)-N-(4-tolylsulphonyl)sulphoximine (106) (Scheme 26) [71][72]. Because these reagents are also known to induce epoxidation when reacted with a ketone or aldehyde

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

• versatility of photoexcited palladium catalysis in radical transformations. Furthermore, the method utilizes the readily available Pd(PPh3)4 complex as the sole catalyst, making it operationally simple and cost-effective. In 2021, Wang’s group introduced a novel transition-metal-free, aldehyde-free strategy

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• acid, and protection of the secondary alcohol as a TBDMS ether (Scheme 9). Intermediate 63 was planned to be derived from Evans’ amide 64 by reducing the amide moiety to a primary alcohol, oxidizing it to an aldehyde, performing a Wittig olefination to install an unsaturated ester, reducing the ester

• to a primary alcohol, and then conducting asymmetric epoxidation of the double bond. Evan’s amide 64 would be synthesized from primary alcohol 65 through a sequence of oxidation to aldehyde, Wittig olefination to an unsaturated ester, hydrogenation of the olefin, conversion of the ester to Evans

• alcohol in 66 was oxidized to its corresponding aldehyde using IBX. Subsequent the two-carbon elongation of this aldehyde yielded unsaturated ester 68 in 91% yield with an E/Z ratio of 90:10. The double bond in ester 68 was reduced using sodium borohydride in the presence of NiCl2·6H2O, affording ester 69

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• that contributes to the overall aqueous solubility and stability of AuCl4−. The precipitation method, according to the authors, is postulated to involve acid hydrolysis of the acetal group of thiolated β-CD to form a reactive aldehyde that takes part in the reduction of the Au3+ cations that get bound

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• enantioselectivities and high diastereoselectivities. A reasonable reaction mechanism was proposed and rationalized the experimental results. Keywords: aldehyde; annulation; aziridine; oxazolidine; ring expansion; scandium triflate; Introduction Oxazolidine derivatives are an important class of nitrogen and oxygen

• The reaction of diethyl 3-phenyl-1-(4-toluenesulfonyl)aziridine-2,2-dicarboxylate (1a) and benzaldehyde (2a) was first selected as a model reaction to optimize the reaction conditions (Table 1). When aziridine 1a (0.2 mmol) and aldehyde 2a (0.3 mmol) in dried toluene (1 mL) were stirred at 10 °C for

• solution of aziridine 1a (0.2 mmol) and aldehyde 2a (0.3 mmol) in dry toluene (1 mL) and the resulting mixture was stirred at 55 °C for 24 h. With the optimal reaction conditions in hand, the scope and generality of both aziridines 1 and aldehydes 2 were investigated (Scheme 2). Different aldehydes 2 were

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

• with nucleophilic cinnamonitrile 149 to give benzocyclooctene 150 via iodonium intermediate 151 (Scheme 46) [86]. 2.2 Oxidative acylations Cinnamic ester or amide preparation could also be achieved by oxidizing cinnamyl alcohol, aldehyde, imine, and ketone as an alternative to the traditional O/N

• Co/Cu nanoparticle-co-decorated nitrogen-doped carbon catalyst (CoCu@NCn) which was used to catalyze the oxidative esterification of cinnamyl alcohol (157) without the need of a base additive (Scheme 51B) [26]. 2.2.2 Aldehyde/ketone oxidation: By employing non-precious transition metals, Wei and co

• cinnamate (44) via an electrochemical method using TBAF as the supporting electrolyte (Scheme 56) [99]. Under these conditions, the aldehyde was oxidized to give an oxonium cation intermediate 176. Moreover, Babu and co-workers (2024) oxidized an imine, cinnamalaldehyde N-tosylhydrazone (177), by using TBHP

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

• the terminal alkene and the conformational strain of forming a bridge[3.2.1]bicycle might be responsible for a selective 6-exo-trig cyclization. From tricyclic compound 4, anti-Markovnikov oxidation catalyzed by palladium led to the formation of aldehyde 5. When treated with p-TsOH, the intramolecular

• presence of silyl and aldehyde groups on the tricycle, it is inconsequential as these groups are either removed or oxidized in subsequent steps. After adjustment of the oxidation levels, the cyclopentenone 45 obtained was subjected to an intramolecular Giese reaction, producing 46 with establishment of the

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• essential tertiary alcohol at C1. The β-hydroxylactone moiety (D ring) in 11 could be introduced through an intramolecular aldol condensation [35] of acetate 12. Ultimately, the preparation of 12 could be traced back to aldehyde 14 through 1,2-Grignard addition with an organomagnesium reagent [36] prepared

• achieved by using (R)-BTM (19), furnishing acetate 18 with satisfactory efficiency and enantioselectivity (37% yield, 85% ee). Finally, iodination of 18 employing Johnsen’s protocol (I2, pyridine) [39] provided α-iodoenone 13 in 89% yield. On the other hand, the synthesis of acetal aldehyde 14 commenced with

• -unsaturated aldehyde and synthesized from 26 via a four-step transformation sequence, including deketalization, reduction, silylation of the primary alcohol and oxidation of the secondary alcohol. For the disconnection of the C2–C7 bond, a two-step protocol involving Rubottom oxidation and PIDA-promoted

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• Scheme 1 and Scheme 2. The newly synthesized compounds were characterized by NMR spectroscopy as well as elemental analysis or high-resolution mass spectrometry. The experimental details and compound data are provided in Supporting Information File 1. Aldehyde 4, in which one of the formyl groups in

• napthalene-1,5-dicarboxaldehyde was protected as an acetal, was prepared through a 5-step reaction sequence. Phosphonium salt 5 [39] and the partly protected o-phthalaldehyde 6 [47] were obtained by previously reported procedures. The reaction of phosphonium salt 5 with aldehyde 6 in the presence of KOH and

• catalytic amount of I2 under an aerated condition. After the photolysis, the acetal moiety was partly cleaved to produce a mixture of acetal 9 and aldehyde 10. The obtained reaction mixture was treated with TsOH in acetone to afford desired fluorinated phenanthrenecarbaldehyde 10 in moderate yield (46% from

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• reagents in the procedures mentioned above. Amino acids can be procured from natural sources by enzymatic synthesis [21], as well as synthetically accessed from aldehyde building blocks via the Strecker synthesis [22], making them attractive starting materials for hydantoin synthesis. Results and

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

• devoted to dimethyl sulfoxide, dihalomethanes, hexamethylene tetramine, and glyoxylates as C1-building blocks, substituting formaldehyde. Review Methanol as a source of formaldehyde There are several reports on the use of alcohols under oxidative conditions as aldehyde surrogates in Ugi and Passerini

• reactions [10]. Oxidation of the alcohol is done in situ to avoid problems regarding the isolation and instability of the aldehyde produced, although undesirable reactions, such as oxidation of the amines or isocyanides or overoxidation of the alcohol, could also be problematic [11][12]. In this regard

• , several efforts have been made to improve the chemoselectivity of the oxidation step. Among the most relevant examples, o-iodoxybenzoic acid (IBX) has been used in Ugi and Passerini reactions to oxidize the suitable alcohol to the desired aldehyde [13]. Alternatively, catalytic amounts of a ternary system