Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• epoxidation of the tetrasubstituted alkene followed by Grieco elimination yielded diene 92. Subsequent oxidation of the hemiacetal, saponification of the lactone, intramolecular epoxide opening, and Hoveyda–Grubbs (II)-catalyzed RCM afforded tetracyclic compounds 94 and its transesterification product 93

• , provided carboxylic acid 113 in a single operation. Subsequent activation of 113 with acetic anhydride, relactonization, and organoselenium-mediated regioselective epoxide opening yielded mono-enone 114, successfully installing the key C9 and C10 chiral centers with the required oxidation states. Notably

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• – was prepared from (+)-pulegone (77) through a six-step manipulation involving epoxidation, epoxide opening with sodium thiophenolate and subsequent concomitant retro-aldol, sulfoxidation, a one pot α-alkylation with acrylonitrile proceeding to thermal syn-elimination of phenylsulfenic acid, ketone

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

• epoxide-opening cyclisation for the oxetane formation (Scheme 11b) [45]. The highest yield was obtained for the PhSH/I2 10:1 activator under unusually mild conditions – the authors believed it is due to the oxa-bridge which facilitates the Lewis acid coordination. In 2001, Rousseau and colleagues reported

• , vinyl, ethynyl or sulphide are sufficient if a superbase such as LIDAKOR or LICKOR is used (Scheme 16) [54][55]. The reaction tends to be remarkably regioselective (in terms of the epoxide opening) and stereoselective, however, it should be treated with caution in case of allyl ethers as they can also

• opened by SnCl4 at −78 °C in a syn manner to give the corresponding chlorohydrins 122, which then upon treatment with BF3·OEt2 underwent the O–H insertion producing oxetanones 123 in good yields. The authors also found that increasing the temperature to rt during the epoxide opening afforded the

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• range of functionalized polyolefins, showcasing the applicability of this xanthylated polyolefin in various reactions, including trifluoromethylthiolation, polymer grafting, Michael addition, and epoxide opening. Amidyl radical from N–X bond cleavage Direct halogenation of C–H bonds is of significant

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

• a fragmentation process for the total synthesis of (−)-phlegmariurine B. A one-pot epoxidation/nucleophilic epoxide opening introduced both a hydroxy group and a chloride across the cyclopentene, producing 14 in 57% yield. After oxidation of alcohol 14 to ketone 15, the Mukaiyama hydration then

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• noted previously [51][52], the reaction depicted in Scheme 1 can proceed via two distinct mechanisms. In the first mechanism, the catalyst initiates epoxide opening, followed by CO2 insertion. The second mechanism suggests that CO2 activation by the catalyst precedes its transfer to the epoxide. To

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• synthesis has been reported for several transformations, such as epoxide opening [56], ketal formation and deprotection [57][58], Mannich reaction [59], intramolecular Sakurai cyclization [60], alcohol oxidation [61], aromatic hydrocarbon nitration [62], imine allylation [63], Knoevenagel condensation [64

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• tested anion–π catalysts. This result was consistent with the stabilization of the anionic intermediates IX and X and the respective transition states on the polarized fullerene surface. Anion–π autocatalysis on fullerenes The autocatalysis of epoxide-opening ether cyclization on π-acidic aromatic

• catalysis. Moreover, epoxide opening polyether cyclizations are among the most impressive cascade reactions in nature [71][72][73]. Best known is the hypothetical cascade XII in the biosynthesis of brevetoxin B [74]. It affords eleven fused ethers by violating the Eschenmoser–Dunitz–Baldwin guidelines [75

• allotropes for catalysis. In contrast to these conclusions made with modified carbon nanotubes, epoxide-opening ether cyclization of 32 occurred on undermodified fullerene 31 (Figure 6) but not on pristine MWCNTs 3 (Figure 9). Modified carbon nanotubes exert their catalytic power because the tethered base

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• synthesis from β-eudesmol (30) through epoxidation to 31, dehydration to 32 and epoxide opening with LiAlH4 yielded (−)-11 (Scheme 9C) [77], contradicting this assignment. Notably, Šorm and co-workers noticed that 11 was racemic, because neither 11 nor any of its degradation products showed optical activity

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• involves the construction of a tetracyclic structure where rings A and B had the correct arrangement, while rings C and D form a bicyclo[2.2.2]octane structure [31]. The correct bicyclo[3.2.1]octane structure was obtained after a key reductive epoxide opening/Dowd–Beckwith rearrangement cascade. The

• reagent and DMDO could induce an epoxidation on the strained olefin. From intermediate 40, the key reductive epoxide opening/Dowd–Beckwith rearrangement cascade could be performed in the presence of an in situ-generated Ti(III) catalyst. The main side-product of this reaction was due to a simple reductive

• bromide coupling. While both Ding and Luo propose a 1,2-shift relying on epoxide ring-opening as key step, each group proposes a different disconnection. For Ding, the rearrangement forms bond C13–C16 through a Ti(III)-mediated reductive epoxide opening/Dowd–Beckwith rearrangement cascade. This allows to

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -pyrone moiety is obtained via ring-closing metathesis reaction of acrylate ester 80, which in turn can be proposed from allylic alcohol 81 via Furukawa’s modified Simmons–Smith cyclopropanation (Scheme 9). The species 81 can be constructed through the sequential epoxide opening and esterification of

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• enantiomerically pure epoxides (S)-7b, (R)-7b, or (S)-7e (Table 2, entries 8–12) at 0 °C. The epoxide opening/Brook rearrangement steps were typically complete after an hour, except for cyclohexene oxide 7f for which the nucleophilic opening and Brook rearrangement steps took 24 h (Table 2, entry 13). Ferrocenium

• enolate formation from 8h,i with s-BuLi, a deuterium quenching experiment with D2O was performed. Analysis by 1H NMR spectroscopy revealed 87 and 91% deuterium incorporation, respectively, indicating that a deprotonation occurred, but the epoxide opening was hampered by the combination of a sterically

• bond cleavage by mCPBA furnishing bicyclo[3.3.0]octandiones 18. The isolation of a mixture of four diastereomers as in the starting material indicates that radical coupling by TEMPO proceeds with exclusive diastereoselectivity (vide infra). Discussion The sequence nucleophilic epoxide opening/Brook

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• cycloaddition, an epoxidation, and a biomimetic epoxide opening. Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step. Synthesis of amphidinolide K (4) by an enyne metathesis route. Trost synthesis of des-epoxy-amphidinolide N (5) [72]. Enyne metathesis between the

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• activation of alcohols [24], epoxide opening [25][26], Friedel–Crafts alkylations [27], dehydrative glycosylation [28] and many other reactions [29][30][31]. The robustness and mildness of organoboronic acid catalysts in comparison to traditional strong Lewis and Brønsted acid catalysts inspired us to

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• acid catalyzed protocols. Many asymmetric versions of epoxide opening by thiols assisted by chiral catalysts have been reported and are part of several reviews [30][31][32][33][34][35][36]. In 1985, Yamashita and Mukaiyama demonstrated the efficacy of zinc L-tartrate as a heterogeneous chiral Lewis

• alternative, Soleiman-Beigi et al. reported an epoxide opening using disulfides in the presence of sodium metal in THF at room temperature (Scheme 23) [59]. The reaction is compatible with different kinds of epoxides possessing substituents such as alkyl, aryloxy and phenylepoxy, and the nature of the

• converted to the epoxide 123, which upon thiolysis with a strategically protected cysteine, gave the regioisomeric hydroxy sulfides 124 and 125 (Scheme 43). Each of these was then converted to natural pteriatoxin A (7) and its analog 126. Epoxide opening to yield β-hydroxy sulfides of unnatural (artificial

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• -catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc). Keywords

• stereocenter on C4, resulting in the desired cis-selective epoxide opening and therefore, galacto-configured azido alcohols 7a and 7b (≥95% de) [22]. Initial limitations in reaction size and yield could have been overcome by switching the solvent from THF, as described in the Miyashita protocol, to EtOH. This

• approach opens up new perspectives for additional modifications: meso-tartaric acid as possible starting material or different epoxide opening protocols, as well as, the selective isotopic labelling are only a few to mention. This convertible synthetic route brings us a step closer to access the whole

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• substituents is of interest. Here we describe optimisation efforts in the synthesis of anti-2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syn-diastereomer. Both targets were synthesised using an epoxide opening strategy. Keywords: acetal isomerization; deoxyfluorination; epoxide

•  1 was high-yielding [17], two disadvantages were apparent. First, the epoxide opening takes 2.5 days at 115 °C and uses an expensive fluoride source (Landini’s reagent [18]: Bu4NH2F3). It was found that Bu4NH2F3 made in-house gave significantly reduced yields. Second, the use of the benzyl ether

• protecting group resulted in a significant increase in mass, and therefore, chromatographic purification of the protected intermediates upon scale-up was inconvenient. As previously reported [17], epoxide opening of cis-2 with Olah’s reagent (HF·py) led to an 80% yield of the fluorohydrin after just three

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• Et3N·3HF according to O’Hagan’s method [34] (Scheme 3). This did effect epoxide-opening to some extent, but the reaction was rather unsatisfactory because it was low-yielding and non-regioselective, which made full characterisation of the product mixture (32/33) impossible. Nevertheless, an analytical

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• have recently been reviewed [34]. We have previously reported syntheses of heliannuols C, D, and E via intramolecular epoxide opening reactions [35][36], but this approach did not translate well to the synthesis of heliannuol A. One of our alternative strategies for the synthesis of heliannuol A was an

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• the C1–C20 seco acid via formation of the C9–C10 bond by an epoxide-opening reaction with an alkyne-derived alkenyl trialkylaluminate. A distinct strategy was also chosen by the Aggarwal group, which connected the linear C1–C11 fragment to the C12–C20 fragment employing their lithiation–borylation

• obtained according to literature procedures [133], thus setting the stereochemistry at C12. The five-step sequence from 20 to vinyl iodide 21 included a (poorly diastereoselective) epoxidation, epoxide opening with a propynyl anion and a hydrozirconation/iodination reaction to generate the vinyl iodide

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• reaction. The ambruticins contain a second hydropyran ring that is established by epoxide opening (see chapter 1.1.3). A further enzyme with similar dehydratase–cyclase activity was recently discovered by Leadlay et al. in the biosynthesis of the polyether ionophore salinomycin (31, Scheme 5) [18]. SalBIII

• building block [34][35][36]. 1.1.3 Epoxide opening: The nucleophilic opening of epoxides is probably the most abundant type of reaction leading to furans and pyrans. It, for example, plays an important role in the biosynthesis of ionophoric terrestrial and marine polyethers (see chapter 1.3). In this

• on the C6 and C7 hydroxy groups during this biosynthetic endgame remains enigmatic [46]. Ambruticin. Another example in which a single epoxide opening event leads to the installation of an individual ring is the formation of the western tetrahydropyran ring in the biosynthesis of the ambruticins

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• reaction followed by the reduction of the triple bond to the trans double bond. Alkyne 7 can be synthesized from alkyne 8 involving an isomerization reaction. Alkyne 8 was easily accessible from (R)-propylene oxide (9) through an epoxide opening reaction with 1-butyne. Results and Discussion In recent work