Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• nitrile oxide. At this stage, it is not clear that the diastereomeric ratio (dr 4:1) may share with the same configuration at the C2 or C2’ position. The mixture of 18 was subjected to reduction of the imine motif by NaBH3CN in AcOH–MeOH and immediately protected with the Boc group. The isolated yield of

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• have been little studied, and are of interest to synthetic chemists. Thus, the interaction of (−)-metaphanine (70) with ammonia in CH3OH at room temperature led to the in situ formation of imine 72, which, as a result of an intramolecular aza-benzilic acid-type rearrangement, was converted in more than

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• optimized [3 + 2] cycloaddition conditions. The primary strategy for the selection of these compounds as catalysts is predicated on their capacity to function as H-bond acceptors and/or H-bond donors. As has been documented in previous research, imine-based templates or [2]rotaxane that possess an amide

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

• ] intermediate 62 (Scheme 14, path a). When a less nucleophilic indole was used as the nucleophile, a Wagner–Meerwein rearrangement occurred, leading to the formation of a pyrido[4,3-b]indole product 63. When Hantzsch ester (HEH) was used as the nucleophile, the imine intermediate 62 was reduced to product 64

• acted as nucleophile, the stable imine–gold–aryl cation–π–π interaction precluded rearrangement and promoted the capture of imine to form spiro[indoline-3,3'-pyridine] derivatives 67. The Ph3PAuCl/AgNTf2-catalyzed cyclization of N-propargyl-tethered amide enynes efficiently afforded four distinct

• Wagner–Meerwein rearrangement from the six-membered spirocyclic intermediate 88. The addition of Hantzsch ester or indole as the nucleophile effectively trapped the imine intermediate 88, preventing Wagner–Meerwein rearrangement and yielding spirocyclic indole framework 90 (Scheme 19, path a). When PPh3

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

• ) to obtain triazolobenzodiazepine which in turn can serve as a cyclic imine for a modified Joullié–Ugi 3-CR with isocyanide and trimethylsilyl azide (TMSN₃) in the synthesis of tetrazole-tethered triazolobenzodiazepines (Scheme 3B). We envisioned that the reaction conditions may need to be modified to

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

• at the anode to generate imine intermediate C. Simultaneously, treatment of 39a with I+ and the following intramolecular nucleophilic cyclization produced C. The elimination of a proton from C afforded the intermediate D. In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), the intramolecular

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

• 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

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

• photocatalysts (Scheme 2). The combination of photoredox catalysis with imine activation enabled the reductive coupling of imines under mild reaction conditions, providing direct access to benzyl and aryl vicinal diamines with good to excellent yields. Organic electrochemistry represents an attractive and

• methanesulfonic acid, which acts as a strong Brønsted acid to selectively protonate the imine nitrogen atoms. This protonation step increases the electrophilicity of the adjacent imine carbons by inductive effect, leading to the formation of a highly reactive diiminium intermediate 4a. When formed, compound 4a is

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

• reaction produced the imine 16a which, upon treatment with Pd(PPh3)2Cl2 and KHMDS, led to furan ring formation and the generation of hetero[7]helicene 17a while maintaining the stereochemical configuration. Through this methodology, a range of elongated [7]- and [8]heterohelicenes 17b–d incorporating both

• resolution of racemic 10-substituted 9,10-dihydrotribenzoazocines featuring both inherent and central chirality, delivering excellent kinetic resolution performance (see 68d–g). During our studies, we serendipitously found that the imine-containing eight-membered azaheterocycles 70, derived from the

• 71 yielded the cyclic intermediate INT-B, which then underwent addition with aniline co-catalyst 73 to form INT-C. The CPA-enabled release of CO2 from INT-C yielded the imine-containing intermediate INT-D, which underwent iterative addition with INT-B, followed by release of CO2 to afford INT-E. The

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

• malononitrile to form benzylidenemalononitrile (BMN). In a typical primary amine-catalyzed Knoevenagel condensation, the amine would undergo imine condensation with benzaldehyde. The imine would then deprotonate malononitrile, and the resulting carbanion would react with the imine, releasing the final product

• undergoes imine condensation with benzaldehyde. B) Mechanism in which the amine acts as a base, deprotonating malononitrile. Estimated conversions of the reactions of isocyanates with the –OH and –NH2 groups of KSU-1 to form carbamates and ureas, respectively.a Comparison of Knoevenagel catalysis results

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

• , Corminboeuf, Samanta, and König [6][31][32][33][34][35]. Although they do not possess an azo bond, heterocyclic imines are worth mentioning in this chapter due to their similarity to the azo-compounds and their straightforward synthesis. Substitution of the azo bond with an imine bond gives rise to

• aryl ring of 11a and 11b yield iminopyrazoles with longer half-lives and negative photochromism (Figure 7, top). This unusual behaviour can be explained by the absence of adjacent non-bonding lone pairs in the imine bond [37]. Conversely, in the case of N-phenyl derivatives 11c and 11d (Figure 7

• , bottom), the thermal lifetimes drop significantly [38]. It is thus crucial to take into account the asymmetric nature of the imine bond and the steric hindrance of the substituents in the design of these photoswitches. For a detailed analysis of the structure–property relationship of these compounds we

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

• 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

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

• nucleophilically attacks the phosphonium in A to generate intermediate B by loss of triphenylphosphine oxide and triflic acid. The nucleophilic sulfonamide in B intramolecularily attacks the generated imine moiety in B to form intermediate C, in which triflic acid may protonate the imine moiety in B to assist the

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

• between β-ketoester 30 and di-tert-butyl azodicarboxylate (31), and the corresponding product 32 was obtained in 99% yield with 88% ee. A plausible reaction mechanism was proposed for this CPA-catalyzed enantioselective Groebke–Blackburn–Bienaymé reaction. As illustrated in Scheme 5b, the imine

• chiral INT-C, which, after imine-enamine tautomerization, led to the formation of final product 28. α-Acidic isocyanide-based transformations De novo arene formation In 2019, Zhu and co-workers developed the first example of catalytic enantioselective Yamamoto–de Meijere pyrrole synthesis [36][37

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

• -plane aromaticity in view of the computed NICS(3, +1) value of −12.0 ppm and diatropic induced ring current (Figure 7a). Interestingly, the analogous reaction involving cis-pent-2-en-4-yn-1-imine, where the terminal CH=CH2 group in the parent system was replaced by an imine CH=NH group, proceeds with a

• the lower barriers computed for the Hopf cyclizations of ene–ene–ynes E=CH–CH=CH–C≡CH where the terminal CH2 group was replaced by a heteroatom (E = NH or O). Figure 8 shows the corresponding ASDs for the parent cyclization (E = CH2) and the analogous process involving the imine system (E = NH). In

• imine system at the initial stages of the cyclization, this term becomes rather similar for both systems at the proximity of the corresponding transition states and therefore, is not responsible for the different barriers. Instead, the cyclization involving the parent system is associated with a much

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

• both normal and inverse-electron demands, depending on the electronic properties of substituents in the aromatic fragments of the dipole and dipolarophile. Our result may indicate a predominant overlap of HOMOdipole and LUMOdipolarophile (inverse-electron demands) in the reactions of the imine 2f. In

• the product of decomposition of the initial imine 2f. No other substances could be identified in this case. In all cases, the 32CA reactions occurred regiospecifically, forming a 1,2,4-oxadiazoline ring, which is consistent with the results of the reactions for similar substrates [36][38]. The

• more electronegative oxygen or nitrogen atoms, both in the HOMO of dipole and dipolarophile [36][39]. In contrast, the carbon atoms have a significantly higher orbital coefficient than the heteroatoms, both in the LUMOdipolarophile and the LUMOdipole. Thus, nitrile oxide tends to react with an imine to

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

• 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

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• addition, even though there was an excess of water as compared to methylamine in the reaction mixture, the nucleophilicity of water molecules is lower than that of the aliphatic amine [22]. Hence, the transimination reaction [23] has occurred reversibly in which the imine (C=N) linkage-containing resonance

• nucleophiles [24]. Therefore, it is reasonable that the transimination reaction between 3a’–e’ and 4 preferentially takes place at the carbon atom of the imine (C=N) linkage instead of the carbonyl carbons at the 2- or 3-positions. Lastly, the covalent bond between the tetrahedral carbon atom and the

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

• , resulting in detachment of the cyanide carbon from the calcium atom to yield an isocyanide complex 9 [55], in which the preferred side of attack on the imine carbon of the hydrazone is already predetermined (i.e., from either Re or Si face). Notably, in both complexes formed from E- and Z-hydrazone, an

• isomer, with a more acute Ca–N–C angle of 92°, has greater resemblance to a (here absent) side-on form (found to dominate computationally for Ca(CN)2 in the gas phase) [54]. Fortunately, that isomer in which the isonitrile carbon is closer to the imine carbon (i.e., the hydrocyanation reaction center

• provisioning for the following reaction step. Hydrocyanation hence proceeds facially with a barrier of only 10.2 kcal·mol−1 via the configuration-determining TS 9-10 by attack of isocyanide at the imine carbon of hydrazone. If the configuration-determining step would be also rate limiting, experimental

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• , we conducted a 5.0 mmol scale reaction and obtained the target product 3aa in 82% yield (Scheme 3). Based on previous reports, a plausible mechanism was proposed. In the presence of a copper catalyst, aniline reacts with cyclobutanone oxime to form an imine intermediate, which undergoes isomerization

• to generate an enamine intermediate. Subsequently, an intermolecular cyclization occurs between the enamine and imine intermediates, ultimately yielding the final target product through an aromatization process (Scheme 4). Conclusion In summary, we have developed an efficient and practical copper

• group tolerance. The optimized reaction conditions, utilizing copper(II) trifluoroacetate as the catalyst and hexane as the solvent, enabled the synthesis of the target products in good to excellent yields. Mechanistic studies suggest a catalytic cycle involving the formation of imine and enamine

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

• under Pd-catalyzed hydrogenolysis afforded diamino acid ester 14 (75% yield) that was likely formed by ring-opening of the unstable N-unprotected 2-aminoproline followed by the reduction of the open-chain imine tautomer. Likewise, the open-chain amino alcohol 15 was formed also upon the reduction of the

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

• –Alder reaction between an imine and an alkene (Scheme 6). Very successfully, the multicomponent version of the Povarov reaction using aldehydes, anilines, and alkenes has been explored in a three-component cascade reaction to quinolines [28][29][30][31] (Scheme 6). Furthermore, protocols have been

• conversion of DMSO to MMS, a wide range of 4-arylquinolines can be synthesized (Scheme 8, path I) [24]. In this reaction, the persulfate ion generates the thionium ion (MMS), which is trapped by a nucleophilic aniline. The loss of methyl sulfide generates an imine intermediate B, which, in turn, reacts with

• ). Additionally, the Tiwari group developed a metal-free protocol using only K2S2O8 as an oxidant for the activation of DMSO to MMS (Scheme 8, path II) [38]. Under these conditions, an alternative mechanism arises in which the imine intermediate B, formed as previously stated through reaction between the aniline

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• formed 17g in good yield and diastereoselectivity with decreased enantioselectivity, likely due to electronic effects. 6-Bromo- and 7-chloro-substituted substrates also provided 17h and 17i in good yields with moderate to good stereoselectivities. Next, Cbz-protected imine 7j was employed in the present

• exchange from tetrafluoroborate to the halonium moiety to form chiral ion pair II. Attack of the chiral nucleophilic intermediate II to imine 7 leads to intermediate III. The latter is protonated by in the situ-formed potassium bicarbonate to form the desired product 17, together with the regenerated

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• yield decreased, possibly due to the formation of imine B, which might be favored by the dehydration effect of the molecular sieves. Conclusion In summary, a regioselective and diastereoselective vinylogous addition reaction of 4-alkenyl-5-aminopyrazoles to alkyl trifluoropyruvate has been studied

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

• popularization of dynamic covalent chemistry in the 1990s [251][252][253][254][255], macrocycle and cage synthesis using reversible reactions [256][257][258][259] like imine formation (Figure 7A) have led to advances in the synthesis of COFs [223][224] and discrete organic cages [260][261][262][263][264][265

• ][344][345], which show early promise for low-symmetry cavities with catalytic potential [42][43][44][340]. Notably, Otte has used semi-stepwise self-assembly via imine formation/reduction to access a robust organic cage with reduced-symmetry and internal functionality able to chelate a copper(I) ion

• quickly identified the triptycenyl-based imine cages of Mastalerz [301] as a strong starting point because: (i) they offered efficient, modular assembly; (ii) all of the complexity could be confined to the privileged triptycene motifs, which would present rigid internal vectors into the cavity for