Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• high concentration of ≈80% acetic acid (pH ≈3), it seemed plausible that activation of the dienone carbonyl group would occur by hydrogen-bonding, rather than complete proton transfer to the carbonyl oxygen lone pairs [29]. We therefore included explicit solvation with acetic acid in our computational

• 1b. Minimized structure of dienone 7 (calculated using the PBE0 functional [26] and the def2-SVP basis set [27] (see Supporting Information File 1 for full computational details)). Modeling of cyclization transition states (the solvating acetic acid molecules were omitted for clarity, and the

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• pyrrolizidine alkaloids with diverse biological activity [6][7][8]. An analysis of experimental and review articles showed that (3 + 2) cycloaddition reactions are carried out, in most cases, using two main strategies for obtaining azomethine ylides, depending on the amino acid derivative used: a free amino

• acid or its ester (Scheme 1). In both cases, condensation of amino acids with carbonyl compounds occurs; however, in the first case, decarboxylation occurs with the in situ formation of azomethine ylides, which subsequently undergo cycloaddition to unsaturated substrates. The advantage of the first

• multicomponent one-pot (3 + 2) cycloaddition reactions involving azomethine ylides from isatins and amino acids [21][35]. The main feature of this review is that we have attempted to consider all currently known systems for generating azomethine ylides based on carbonyl compounds and amino acid derivatives (or

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• hydroxy group allowed the synthesis of compound 1 from 4 in nine steps. Selective acid-mediated 5,10-transannular cyclization of 5 followed by hydration reaction furnished both products 2 and 3 in two steps. Keywords: chemoenzymatic synthesis; chiral pool; isopentenol utilization pathway; terpene

• condensation of dimethylallyl pyrophosphate (DMAPP) with different numbers of isopentenyl pyrophosphate (IPP) [6]. Two naturally existing pathways, i.e., the methylerythritol phosphate (MEP) pathway and mevalonic acid (MVA) pathway, as well as artificially designed pathways, such as the isopentenol utilization

• pathway, have been adopted to provide the two key five-carbon building blocks DMAPP and IPP. With the recent advancement in the field of synthetic biology, more chiral terpenes (e.g., guaia-6,10(14)-diene [7][8], drimenol [9][10], and ent-atiserenoic acid [11] as shown in Figure 1b) became easily

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

Beilstein J. Org. Chem. 2026, 22, 672–679, doi:10.3762/bjoc.22.51

• fails to yield hits [9]. While the term peptidomimetics has been used to describe a variety of molecular classes, including modified peptides and molecular scaffolds for display of amino acid side-chains, this Perspective focuses on non-peptidic small molecules with the appropriate shape and

• translation (also known as RaPID, random non-standard peptides integrated discovery [4]). Key interactions that comprise the pharmacophores were experimentally determined by alanine scanning and other amino acid substitutions to explore SAR, coupled with analysis of co-crystal structures obtained for the

• bound complexes, including computational analysis of the amino acid interactions (SiteMap [16]) and hydration in the binding pocket (grid inhomogeneous solvation theory [17] in AmberTools [18]). The pharmacophores were then used as the basis for virtual screening with docking (Glide [19][20]) to obtain

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• ) under blue-light irradiation in acetonitrile (Scheme 1d) [17]. Also, photoelectrochemical trifluoromethylation procedures using trifluoroacetic acid or its salt were published recently [18][19]. Inspired by these methodologies, we sought to combine their advantages to develop a metal- and base-free

• originally reported by Bazyar and Hosseini-Sarvari [20]. A comparison of the atom efficiencies of various CF3 sources clearly indicates that trifluoroacetic acid (TFA) is the most atom-efficient and, moreover, the least expensive CF3 source (Table 1). Although iodotrifluoromethane, triflyl chloride, and the

• Langlois and Ruppert–Prakash reagents formally exhibit higher atom efficiencies than trifluoroacetic anhydride (TFAA), they are significantly costlier and challenging to prepare. In contrast, trifluoroacetic acid generated as a by-product can be readily converted back into TFAA, especially in large-scale

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• 289, 9000 Gent, Belgium 10.3762/bjoc.22.48 Abstract The first NHC–Cu-catalyzed decomposition of formic acid (FA) is reported. In the presence of PhSiH3, only hydrogen is generated while CO2 is captured by a silane species. The decomposition of an equimolar mixture of FA and an amine provided an

• equimolar mixture of H2 and CO2. The efficiency of the catalysis showed to be strongly dependent on the nature of the amine. Keywords: copper N-heterocyclic carbene; formic acid dehydrogenation; hydrogen storage; metal hydride; silanes; Introduction The discovery and utilization of alternative and

• realization of a hydrogen economy [6][7]. Amongst the various H2 sources investigated to date, formic acid (HCO2H, FA) is considered one of the most promising. Indeed, FA contains 4.4% H2, is inexpensive and is liquid under ambient conditions, thus easy to handle and transport. In addition, the CO2 generated

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• undesired alkylation of the base and significantly improved the isolated yield up to 84%. Introduction of an acetic acid handle was then achieved via alkylation with bromoacetic acid under DIPEA mediation, giving intermediate 6, which served as the common attachment point for linkers 7–10 (for full

• corresponding triflate using triflic anhydride, followed by Suzuki–Miyaura cross-coupling with phenylboronic acid to give 16 in 59% yield (Scheme 1). Boc removal from intermediates 11–14 enabled attachment of the αD binder aldehyde 16 via reductive amination. Interestingly, NaBH(OAc)3 had performed well in the

• yield acid S13. Isothermal titration calorimetry (ITC) revealed that S13 bound CK2α with a dissociation constant (Kd = 600 nM) comparable to that of CAM4066 (350 nM; Figure 1C). This indicated that the exit vector modification and linker installation were well tolerated. Co-crystallisation of S13 with

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• nucleophilic aromatic substitution with thiophenols followed by oxidation with m-chloroperbenzoic acid (mCPBA). The scope of the reactions was explored, demonstrating high yields across a variety of functional groups and substituents. Optimized conditions enabled selective oxidation of thioaryl groups to

Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• ) calcium ion with amino acid side chains – that might also be in part be responsible for the lack of tweezer binding to Lys-121 – but also represents a new binding mode for the tweezer moiety. The (hydrated) Ca2+ ion is apparently too large to enter the cavity of the tweezer ring, in contrast to larger Cs

• 2b on K-121 leaves more room for stabilizing packing effects. Lys-122 is also located in the vicinity of the H3-T3ph binding site; although it forms a protein contact with Asn-118, there is plenty of room around it in the crystal structure (Figure 4). However, to target this amino acid, the linker

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• , pharmaceutical compounds, and chiral ligands. The Lewis acid-catalyzed ring-opening reaction of cyclohexene oxide by MeZH (Z = O, S, and NH) is well known [20]. However, studies on large-sized bicyclic epoxides remain relatively limited in the published literature. In our previous study, we performed the ring

• each elementary reaction step along these routes were computed. The acid-mediated ring-opening reaction in the isomeric epoxides 9, initiated by protonation, can follow two possible pathways – either along the intermediate 12 or along the intermediate 15. There is a possibility of two products being

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• synthesis of 4 and its possible isomer 3, the required compounds 1 and 2 were synthesized as a mixture of the isomers starting from chromene 5, briefly heated in a closed microwave apparatus with catalytic amounts of acetic acid. Forced heating of 5 in acetic acid or use of stronger acids lead to the

• made to cyclize 5 into melifolione B (2) with the following results (Scheme 1) Heating of 5 in DMF at 100 °C yielded melifolione A (1) with traces of melifolione B (2). When 5 was heated in acetic acid at 80 °C, only benzoxocin 6 could be isolated. Reaction of 5 with catalytic amounts of p

• -toluenesulfonic acid at 80 °C in toluene afforded benzoxocin (7) as the only product. On the other hand, melifolione A (1) was completely decomposed under these conditions. Irradiation of 5 in methanol with UV-light (300 nm) for 3 days at room temperature gave melifolione B (2) with traces of melifolione A (1

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• modern approaches towards the key fragments and total synthetic strategies for 1 in recent years. Review In 2016, Konda and co-workers reported two approaches for the assembly of the tetrasubstituted tetrahydrofuran unit of 1 (Scheme 2 and Scheme 3) [72]. For the first path, (S,S)-tartaric acid (13) was

• used as a starting material and was protected as acetonide within the first step to enable the reduction of both acid moieties towards 14 (Scheme 2). Bn-protection, followed by oxidation and olefination yielded sulfone 15, which was vinylated leading to 16 as a single diastereomer. Further Grubbs

• the secondary alcohol unit of 71 was changed via oxidation and stereospecific reduction, then 1,4-reduction of the enone and treatment with camphorsulfonic acid led to fully cyclized intermediate 72 as a single isomer. During this process the acetate groups were cleaved off and had to be reinstalled

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• extractants. Here, we report the design and synthesis of PCP HA, a phenoxycalix[4]pyrrole scaffold functionalized with four hydroxamic acid (HA) groups, and evaluate its uranium(VI) extraction potential. PCP HA was synthesized from its ester precursor (PCP E) via hydroxyaminolysis using KOH, achieving a 95

• , removing up to 95% of uranyl(VI) from aqueous solutions (1 mM) at acidic pH, likely due to the strong coordination provided by its hydroxamic acid groups. Further studies revealed that the extraction efficiency also depends on the ligand-to-metal molar ratio. These findings establish PCP HA as a promising

• supramolecular material for the removal of uranyl from aqueous media. Keywords: gamma spectroscopy; hydroxamic acid; phenoxycalix[4]pyrrole; solid–liquid extraction; uranyl(VI) extraction; Introduction Over the past few decades, supramolecular chemistry has advanced intensively establishing itself as a central

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• routes (Scheme 1) [14][15][18]. Intermediates 5–7 were prepared in a manner analogous to Smalley et al. [14]. The first step in the linker synthesis for Au–(CI-994) involved a monoprotection of nonanedioic acid with a benzyl group to give 5 which proceeded in moderate yield due to the formation of the

• dibenzylated by-product. Compound 5 was then coupled to the CI-994 intermediate 3 via HATU-mediated amide bond formation to produce 6 in good yield. Removal of the benzyl protecting group was performed by catalytic hydrogenation and acid 7 was obtained in near quantitative yield. Intermediate 7 was converted

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• carboxylic acid derivatives (Scheme 2b) [43]. They revealed that ortho-alkoxy substitution on the benzene-derived alkyne markedly enhanced both reactivity and enantioselectivity, while incorporation of a naphthyl substituent into the diyne enabled access to remote biaxially chiral molecules. Subsequent

• studies have further broadened the synthetic toolbox for remote biaxial chirality. Du and co-workers designed a series of chiral phosphoric acid catalysts derived from protected axially chiral diols 13, employing a boronic acid-mediated coupling strategy to construct remote biaxially chiral phosphoric

• polarized BOP bis(2-oxo-3-oxazolidinyl)phosphonic substituent and the extended π system in the arylboronic acid coupling partner. In 2018, Razler and co-workers described an approach for the synthesis of an architecturally complex API 57 having multiple chiral axes (Scheme 14) [53]. Their strategy relied on

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• . Glutaminases catalyze the hydrolysis of glutamine to glutamate, which supports the biosynthesis of amino acids, lipids, and glutathione and can also be oxidatively deaminated to α-ketoglutarate and enter the citric acid cycle. The “glutamine addiction” of cancer cells has made glutaminase an attractive

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• with 2,4,6-trihydroxyacetophenone as a starting material undergoing hydroxy protection, α-bromination, construction of α,β-epoxy carbonyl products via the Darzens reaction, acid-mediated deprotection, and cyclization to afford the target compounds. This method is highlighted by satisfactory overall

• -epoxycarbonyl intermediates. The latter undergo simultaneous deprotection and cyclization by treatment with acid to afford the targeted trans-(±)-taxifolin and its derivatives [19][20][21][22][23][24][25][26][27][28][29][30] (Scheme 1a). Although this synthetic route is efficient, a significant drawback is that

• via Darzens reaction. Subsequent acid-mediated deprotection and cyclization then afforded the target compounds. Compared with the widely used method involving peroxides reported earlier, the present method is highlighted with avoidance of the use of peroxides, therefore enabling safe scale-up and

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• -alkene 7 in 81% yield. The hydroxy group of 7 was substituted with chlorine using oxalyl chloride in DMF, and the TIPS group was removed by treatment with hydrochloric acid to afford the chloroalcohol 2a (74% yield in two steps). After several attempts to cyclize compound 2a via Williamson etherification

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• compounds, selenoproteins, incorporating selenocysteine, the 21st amino acid, are of special importance due to their essential role in various biochemical processes [16][17]. Inspired by natural biosynthetic pathways, synthetic chemists have developed novel low-molecular-weight organoselenium compounds

• methylseleninic acid (1) has emerged as a promising drug candidate for the treatment of triple-negative breast cancer (TNBC) [27]. In addition, the classical organoselenium compound diphenyl diselenide (2) has shown significant anticancer activity against the MDA-MB-231 breast cancer cell line [28]. Very recently

• significant negative character that enables it to form a hydrogen bonding interaction with the active site amino acid residue of the proteins. MEP analysis of compounds 7 and 8 The molecular electrostatic potential (MEP) maps of compounds 7 and 8 are depicted in Figure 6a and 6b, respectively. The MEP

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• persilylated propargyl ethers 7–10 from precursors 2–5 (Scheme 1). Expectedly, (ipso-)nitration of calixarenes 6–10 by mixtures of fuming nitric acid and glacial acetic acid in dichloromethane solutions could potentially be complicated by both the incomplete conversion of the starting materials and also by

• formation of side products, due to acid-promoted cleavage and undesired transformations of the TBS-protected propargyl groups and/or due to unwanted oxidation/nitration of the calixarene core [93]. Indeed, nitration of calixarene 6 has been reported to furnish the desired wide-rim exhaustively nitrated

• calix[4]arene 11 having four TBS-protected propargyl groups at the narrow rim in only moderate yield of 37% [9]. In our hands, according to the NMR spectra of the reaction mixture, under the reported conditions (>30 equiv of fuming HNO3 per calixarene aromatic unit in a 1:1 dichloromethane/acetic acid

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• the human body could be realized and are presented in Table 5. According to Table 5, compound 1 is expected to interact with three nucleic acid receptors and three stress signaling pathways with high probability. However, the cytotoxicity of compounds 7 and 9 is likely not due to interactions with the

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• ] cycloaddition of azomethine ylides at various vinyl sulfones were well studied [38][39][40][41], a method for the preparation of 3-sulfonylpyrrolidines from β-ketosulfones was previously unknown. We synthesized a number of pyrrolidines 2a–f in 83–97% yield, which were purified by an acid-base extraction (Scheme

• 4q–t in 61–87% yields. It should be noted that the leaving 3-benzoyl group formed a methyl benzoate when the reactions were performed in methanol. We also observed the formation of S-butyl benzothioate in the reaction mixture in case of 4q. These by-products were readily removed by an acid-base

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• unsymmetrical oxaza[8]helicenes Building on Zhang’s facile acid-mediated carbazole synthesis [53], in which aniline derivatives react with p-benzoquinone to afford 3-hydroxycarbazoles [54], we employed a closely related substrate. Specifically, N-(p-tolyl)phenanthren-3-amine (2) – prepared from 3

• -bromophenanthrene (1) via Buchwald–Hartwig amination with p-toluidine under Pd catalysis [55] – was subjected to phosphoric acid-mediated annulation with p-benzoquinone to give the hydroxycarbazole derivative 3 through a tandem Michael addition/ring-closure sequence. After rapid optimization of key parameters (see

• structures). Aromaticity of oxaza[8]helicenes: (A) NICS(0)zz and NICS(1)zz values of 5a and 5b calculated at MN15/6-311G(2d,p)/SMD=chloroform level of theory; (B) ACID plots calculated at the B3LYP/6-311G(d,p) level of theory (isosurface value: 0.05). (P/M) Enantiomerization process of 5a (A), 5b (B), 6a (C

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• of conventional, non-activated amides remains far more difficult. This review summarizes recent advances over the past decade in the activation and cleavage of non-activated amide C–N bonds for their conversion into diverse carboxylic acid derivatives. Key strategies covered include transition-metal

• secondary and tertiary amides with octanol catalyzed by CeO2, utilizing the advantage of its cooperative acid–base functionalities (Scheme 2) [46]. Under the optimized conditions, N,N-dimethylbenzamide (3) and N,N-diethylbenzamide (4) were smoothly converted to octyl benzoate (1) in 93% and 95% yield

• of CeO2 to attack the carbonyl carbon, leading to cleavage of the C–N bond (B). Subsequent nucleophilic attack of the octoxide anion on the activated carbonyl center (C) then furnishes the ester product. Later, the same group found that niobium could also serve as a heterogeneous Lewis acid catalyst