Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• aldehyde 3. This linear aldehyde would be activated by an acid to trigger a key Prins cyclization with the trisubstituted olefin through reaction model 3 and generate a putative tertiary carbocation to be trapped by the chiral alcohol, providing bicycle 4 stereoselectively. Finally, the last olefin would

• approach. This key reaction mimics the plausible biosynthetic pathway and demonstrates great efficiency and sole diastereoselectivity, showcasing the plausibility of the biosynthetic proposal. Further redox manipulations of the last olefin and deprotection ultimately provided chabranol. To clearly confirm

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

• by the anomeric effect [23] in the tricyclic scaffold. Compound 13 could be produced from olefin 14 via cross-metathesis. The regio- and diastereoselective connection of C8 and C12 in compound 14 could be realized through a transition-metal-mediated oxidative radical cyclization through TS-1 from β

• , compounds 14 and 20 were evaluated for the cross-metathesis of the olefin moiety in 14. No reaction occurred and the desired product was not detected (not shown), presumably because of the steric hindrance from the TBS group. Following the removal of the silyl group, cyclopentanol 19 underwent the cross

• controlled by the stereoelectronic effect of the axial hydroxy group at C11 (Scheme 4) [28]. First, β-keto ester 21 was synthesized (Scheme 5). Cross-metathesis of allylic alcohol 18 and olefin 28 with the assistance of the Hoveyda–Grubbs second-generation catalyst delivered the desired product 27 in 68

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

• into alcohol 170 in nine steps. Subsequent epoxidation of olefin in 170 followed by acid-mediated cyclization provided compound 171 bearing a tetrahydrofuran ring. An eight-step transformation then yielded compound 172. Next, epoxidation of olefin of 172 with Shi’s dioxirane (generated from ketone 173

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

• conducted a thorough evaluation of the stability of the helical chirality across the synthesized quinohelicenes, indicating a high racemization barrier. In 2024, our group further extended the CPA-catalyzed sequential Povarov reaction and aromatization strategy by using 2-vinylphenols 14 as the olefin

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• chiral HPLC. This confirmed that no erosion of enantiomeric purity had happened during the deprotection stage. With the enantioenriched vinyloxazoline S-6 in hand, we explored the reaction scope involving its electron-deficient double bond. Unfortunately, the olefin appeared unreactive or gave a mixture

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• [20], or, more recently, (iii) prepared via an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction (Scheme 1A) [18]. The reported synthetic route relies on an initial 4-step preparation of the isonitrile precursor, which was accomplished in an overall yield of ca. 14%. The

• . 20% (4 steps) relative to an overall yield of ca. 5% via the preparation of the isonitrile followed by the Fe hydride initiated isonitrile–olefin intramolecular coupling reaction [18]. Protection of the indole nitrogens with the Boc group was preferable to the use of benzyl protecting groups since

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

• 34f could be used as the starting material to prepare the axially chiral olefin-oxazole 37, which might be a potentially useful ligand in asymmetric catalysis. A possible stereochemical model was proposed as well, involving synergistic activation of both the alkynyl ketone and isocyanoacetate by the

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• straightforward reactions. Complementarily, the Review article by Jang and Kim provides a deep understanding of recent advances in the combination of electrochemistry and copper catalysis for various organic transformations [3]. Their contribution elaborates various C–H functionalizations, olefin additions

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• containing one or two exocyclic olefin units. Owing to the transformation of carbonyl groups, the resulting products exhibit several unique physical and chemical properties: (1) the enhancement of configurational stability, (2) the appearance of fluorescence, and (3) the reductive carbon–carbon-bond

• CBBC 1 with 1.2 equiv of methylenetriphenylphosphorane afforded mono-olefin 3 in 49% yield as well as an internally functionalized dibenzo[g,p]chrysene (DBC) derivative 4 in 5% yield (Scheme 1). The use of an excess amount of methylenetriphenylphosphorane (5.0 equiv) afforded compound 4 in a higher

• yield of 50%. In addition, the reaction furnished bis-olefin 5 in 2% isolated yield which is lower than the estimated yield by 1H NMR measurement of the crude mixture (11%). This is due to the partial loss of the product during purification to remove a trace amount of DBC 2, which was generated as a

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

• previous need for strong base-induced alkylations with alkyl halides. The protocol is similarly mild, employs a Brønsted acid catalyst and affords the ether products 144 in moderate to high yields. In 2018, Shenvi and colleagues reported a Markovnikov-selective olefin hydroarylation based on an

• oxygen and a subsequent proton transfer affords the aromatic heterocycle. The authors also devised a modification to this procedure for olefin precursors which were difficult to prepare: this alternative uses cross-aldol adducts 180 between 3-oxetanone and a ketone, and the ring opening and dehydration

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

• the target products 26h, 26i. Additionally, replacing the methyl group on the acrylamide olefin with a phenyl group resulted in a 55% yield of product 26j. Focusing on N,N-dimethylanilines, -CH3 and -Cl substituents at the para-position of dimethylanilines were amenable to the system, yielding the

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

• sediment in Yalongwan, China [22]. The C14–C15 olefin geometry of borrelidins G and H (Table 1, entries 10 and 11) exhibited a Z-configuration, as confirmed by NOESY correlations. Borrelidins J–L (Table 1, entries 13–15) were isolated from an endophytic Streptomyces sp. NA06554 from Aster tataricus in Aba

• 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

• -metathesis reactions in the study exhibited high E-selectivity. As a result, the reaction of (Z,E)-134 with olefin 135 provided the desired product 136 in 56% yield, with a (Z,E)/(Z,Z) ratio of 4:1 (Scheme 21). Compound 136 was subsequently protected as a TBS ether, 137 [35]. The aldehyde counterpart 147 for

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

• )-cinnamic acid esters 445–448 in excellent yields via E-to-Z photoisomerization mediated by the photocatalyst (Scheme 90) [152]. Nguyen and co-workers (2019) employed iodine to catalyze the intermolecular olefin-carbonyl metathesis reaction of benzaldehyde (449) and acrylate 450 to give the corresponding

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• Advanced Academic Research (IAAR), Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan 10.3762/bjoc.21.83 Abstract In this study, we implemented the P,olefin-type chiral ligand (aR)-(−)-6, which contains a cyclohexyl group and a cinnamoyl group on the nitrogen atom, in the Pd-catalyzed

• the resulting product (S)-13a in the presence of FeCl3 as the catalyst, the corresponding malononitrile derivative (S)-16 was obtained without any loss in optical purity. Keywords: asymmetric allylic amination; axial chirality; isatin; palladium catalysis; P,olefin-type chiral ligand; Introduction

• ligands with axial chirality for Pd-catalyzed asymmetric allylic substitution reactions. For example, the Zhou group reported a P,olefin-type chiral ligand 3 with C–C bond axial chirality for this reaction (Figure 2) [27]. Additionally, we have recently reported chiral ligands with C–N bond axial

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

• unpurified reaction residues showed a complex mixture of products. There were some signals suggestive of terminal alkenes, implying that olefin transposition was a competing pathway. With alkyne substrate 59, decomposition occurred, and the 1H NMR of the unpurified reaction mixture was illegible. With

• , which attacks the pendant olefin to form an aziridinium cation (Scheme 2). A sulfonate counter-anion then opens this aziridinium ring in an exo-selective, SN2 reaction. We were successful in scaling the reaction from 0.3 mmol to 11.5 mmol (38-fold increase) without any erosion in yield or selectivity

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

• at 0 °C. In the same year, Lu's research group reported a temperature-controlled site-selective olefin hydroalkylation reaction (Scheme 17) [46]. By adjusting only the reaction temperature, different skeletal structures of nitrogen α- and β-alkylated products could be obtained from the same olefin

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• to the parent allyl group, a variety of 2-substituted electrophiles 31 could be applied. These included those bearing alkyl groups of varying steric demand, halides, and both electron-rich and electron-poor aryl substituents. The olefin coupling partner scope was equally impressive, tolerating

• copper complex formation and subsequent selective olefin insertion results in the high levels of enantioselectivity (98:2 er) observed experimentally. DFT calculations further elucidated the origin of the high diastereoselectivity (up to 96:4 dr) in the allylic substitution step (Scheme 13b). Analysis of

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• coupling, and finally leads to the target pheromones by olefin oxidation with RuCl3/NaIO4. Results and Discussion The retrosynthetic analysis of the aggregation pheromone (4R,8R)-1 is shown in Scheme 1. Obviously, the target pheromone (4R,8R)-1 could be synthesized via an oxidation of chiral terminal

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

• of side reactions. This latter advantage has been notably exploited in the case of ring-closing olefin metathesis reactions, where Weizmann et al. utilized the photothermal response of plasmons from gold nanoparticles to activate the catalyst [17]. This approach contrasts with the work of Rovis et al

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• production of the anticipated products in yields ranging from moderate to good (3e–h). Afterwards, we shifted our focus to substrates containing a single imidazole ring and discovered that the radical difluoromethylation and subsequent cyclization of unactivated olefin-containing imidazoles proceeded

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• functionalities were well tolerated in this transformation (26e–g). Moreover, an olefin-containing terminal alkyne was suitable to afford product 26h, demonstrating excellent chemoselectivity. However, the formation of 26i was not observed under the standard reaction conditions. Instead, the decomposition of

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• olefin addition reactions [20] conducted by various research groups, contributed to this area of research. Recently, the coupling reactions of C(sp3)-based electrophiles were explored using dual photoredox and copper catalysis, achieving selective radical coupling reactions involving alkyl halides [21

• catalysis to organic synthesis, focusing on recent developments in Cu-catalyzed electrochemical reaction categorized into four types: 1) C–H functionalization, 2) olefin addition, 3) decarboxylative functionalization, and 4) coupling reactions (Figure 3). This review aims to provide insight into the

• bromine radical attack that leads to the formation of a cationic brominated copper complex 77. Anodic oxidation and subsequent proton transfer provide the desired product 73 and regenerate the copper catalyst. Olefin addition Hydrofunctionalization and difunctionalization of alkenes are valuable methods

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available

• ; Introduction The construction of C(sp3)–C(sp3) bonds is a highly important target in synthetic organic chemistry. Historically, polar conjugate additions have been a benchmark method for constructing these bonds by functionalizing an electron-deficient olefin [1][2][3]. Recently, however, radical-based

• pathway for the functionalization of an electron-deficient olefin is the Giese reaction (Figure 1) [6][7]. This reaction involves the hydroalkylation of the olefin via radical addition (RA), followed by either hydrogen-atom transfer (HAT) or single-electron transfer (SET) and protonation. Traditionally

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• methoxy group (δH 3.81), six methylene signals (δH 3.33, 3.20, 3.14, 2.21, 1.91, 1.63) and one exchangeable proton triplet (δH 8.04) that was indicative of a secondary amide [7]. Additionally, signals for one isolated trans olefin (δH 7.33, 6.66) and one aromatic signal (δH 7.89) that integrated for two

• carbons (δC 134.5) (see Figure 2). Observation of three-bond correlations in the HMBC spectrum between the olefin protons and aromatic ring carbons (δH 7.33 to δC 131.6 and δH 6.66 to δC 134.5) linked the olefin moiety to the symmetrical 1,3,4,5-tetrasubstituted phenyl system. ROESY and HMBC correlations

• ]. The 13C NMR (Table 1) data of 5 displayed six aliphatic carbons (δC 35.9, 26.1, 44.8, 46.3, 21.1, 30.4) and two carbonyl signals (δC 164.9, 173.6). Similarly to the other ianthelliformisamines, the aromatic (δC 131.6) and olefin (δC 124.5, 135.2) carbons were observed [7]. COSY correlations associated

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• addition to the application of isocyanides in a variety of MCRs, one of the unique reactions involves the formation of zwitterions from isocyanides upon reaction with acetylene and active olefin compounds such as alkyl acetylenedicarboxylates and gem-diactivated olefins. Due to having nucleophilic and

• solvent- and catalyst-free conditions (Scheme 1d). Results and Discussion Synthesis Dibenzoxazepine as imine component, cyclohexyl isocyanide, and the gem-diactivated olefin (2-benzylidenemalononitrile) were selected as the starting materials to screen the reaction conditions (Scheme 2, Table 1). First

• electron-donating substituents (Scheme 3). The cause of this phenomenon is probably related to the electron-widthdawing effect of these substitution groups in olefin, which affects the nucleophilic attack of the isocyanides. When a carboxylate substituent was present instead of the carbonitrile in the gem