Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• introduce another side chain, affording a diene intermediate. A subsequent ring-closing metathesis (RCM) reaction formed the cyclopentene ring, and one pot protection of both carbonyl groups with ethylene glycol provided bis-ketal 55. Notably, due to steric hindrance, only one carbonyl group could be

• transpositions [31]. Starting from (S)-carvone (67), reaction with allyl bromide introduced an allyl group to give 68, which was then converted to the bicyclic compound 69 via a ring-closing metathesis (RCM) reaction followed by one-pot epimerization at the α-position of the carbonyl group (Scheme 7

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

• -ryanodol, cinnzeylanol, and cinncassiols A,B In 2014, the Inoue group at the University of Tokyo reported a synthetic strategy for ryanodol (4) that leveraged substrate symmetry design, employing intramolecular radical coupling and olefin metathesis as key steps [46] (Scheme 4). Recognizing an embedded

• -alkoxy bridgehead radical addition then installed an allyl fragment, and ring-closing metathesis (RCM) smoothly formed the C ring to complete the core skeleton. The total synthesis was finalized by installing the four remaining stereocenters (C2, C3, C9, and C10). The specific synthetic route is as

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• lactone 13 through allylic oxidation and cross metathesis. For the construction of the cyclopentene ring, an alkylidene carbene-mediated C–H insertion would be applied [35]. The synthetic route could be traced back to β-lactone 14, which contains two continuous stereogenic centers with trans configuration

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

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

• transition-metal complexes such as the Grubbs’ second-generation metathesis catalyst, NHCs are now also well-established as organocatalysts. With the first application pre-dating the unambiguous characterization of a free NHC by nearly 50 years, NHCs can facilitate numerous synthetically attractive

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

• -selective cross-metathesis, respectively [9]. In general, racemic cyclopentanol precursors (A ring system, prepared in 6–9 steps) have been used to form the polyfunctionalized tricyclic frameworks incorporating contiguous stereocenters. In previous syntheses, the efficient construction of the cyclopentanol

• 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

• were developed. A straightforward transformation was designed involving a cross-metathesis of the C13–C14 double bond and a palladium-catalyzed decarboxylative allylation [32] as the key steps. With 14 in hand, we investigated the feasibility of cross-metathesis of the C13–C14 double bond. Initially

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

• . PPL-catalyzed desymmetrization of 10 with vinyl acetate yielded monoacetate (R)-11 in 41% yield (94% brsm) with 78% ee. Diene 12 was prepared from (R)-11 via a ten-step sequence. The following ring-closing metathesis (RCM) reaction catalyzed by Grubbs catalyst 13 converted 12 into the bicyclic

• intramolecular cyclization of 16 generated benzofuran 17 in 83% yield. After protecting the phenolic hydroxy group of 17, cross-metathesis (CM) with allylic alcohol 18 catalyzed by 13 furnished intermediate 19. Desilylation of 19 produced heliannuol G (20) and heliannuol H (21), with the structure of 21

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• macrocyclic crown ethers that are attached at the 3,3'-positions via additional phenylene spacers (see Figure 1e) [35][44][45]. Macrocycles M1b with a single BINOL unit were generated from the corresponding diol 2 by attachment of allylated linkers, followed by ring-closing metathesis [46][47][48][49][50

• BINOL core is slightly distorted (∠C2–C1–C1'–C2' = −79.2(3)°). In summary, we could obtain the desired macrocycles M1 containing a single BINOL unit in satisfying yields (11–75% from diols Me/H/iPr-2). The previously published route based on ring-closing metathesis gave macrocycle M1b (see Figure 1e

• synthesis of the allyl tosyl ethylene glycol (see Figure 1e) can be avoided and the bistosylated ethylene glycol 8 (available in one step) can be used instead. Secondly, the ring-closing metathesis was substituted for an operationally simple Williamson reaction. This results in macrocycles with regular

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• thia-bridged triarylamine[4]helicene-functionalized polynorbornenes 63a–c via ring-opening metathesis polymerization (ROMP), introducing helicene chirality into polymer backbones with tunable electrochromic behavior [78]. These polymers exhibit reversible pH-responsive color changes. For instance, 63a

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

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

• and deprotection steps, functional group transformations, stereocontrolled allylation, cross-metathesis, and Horner–Wadsworth–Emmons (HWE) olefination. This method highlights the power of catalytic stereocontrol, achieving the complex architecture of borrelidin fragments with efficiency and precision

• diastereoselectivity (20:1 dr). Direct cross-metathesis of 111 with acrolein was envisioned as an efficient method to introduce an aldehyde functionality adjacent to the alkene moiety without prior protection of the free allylic alcohol. This hypothesis was successfully realized by reacting 111 with acrolein diethyl

• using cross-metathesis In 2008, Iqbal and co-workers conducted a synthetic study in which they successfully synthesized the C3–C17 fragment of borrelidin using a cross-metathesis reaction [35]. In the retrosynthesis, compound 132, representing the synthetic target, was realized through an addition

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

• construction, alkyne hydrogenation, ylide and carbene reaction, metathesis, E/Z isomerization, and other methods, including Cα and Cβ functionalizations. Preparing various functional group-tethered aromatic groups can be achieved by directly installing an aromatic group via cross-coupling reactions and other

• are cis-coplanar resulting in the Z-isomer product. 3.1.4 Metathesis reactions: Metathesis reactions are one of the most crucial approaches to preparing olefins. Grubbs and Grubbs–Hoveyda catalysts are among the most frequently used catalysts for the stereoselective construction of C=C bonds. Moreover

• , metathesis reactions have also been applied to stereoselectively synthesize cinnamic acid derivatives. For example, Lakhdar and co-workers (2022) combined E-selective Grubbs second-generation catalysts (cat 7) with photocatalyst (PC-4) to convert styrenes and methyl acrylate (444) into the corresponding (Z

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• (Scheme 3a). Based on the well accepted metathesis reaction of Cu(I) alkoxides with B2pin2 and the reactivity of the resulting Cu–Bpin complex towards α,β-unsaturated esters and hydrocarbons [8][9][10][11][12][13][14][15], we hypothesized that the first step of the reaction may deal with the insertion of

• species A which is in equilibrium with the Cu–O enolate B [11]. In the presence of excess of LiOt-Bu, a salt metathesis reaction between this base and intermediate B generates lithium enolate C and LCuOt-Bu to close the copper catalytic cycle. The formation of a lithium enolate is consistent with the

• summary, we have discovered an unanticipated Cu–Bpin-promoted diastereoselective dimerization of 4,4-dichloro-2-butenoic acid derivatives. The reaction occurs via initial Cu–Bpin insertion followed by keto–enol isomerization and salt metathesis to generate a lithium enolate which is then trapped by a

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

• metathesis with HBpin to afford a vinylboronic ester intermediate 45 alongside the regenerated L*CuH catalyst, completing the first catalytic cycle. Subsequently, a ligand-controlled regioselective migratory insertion of L*CuH into the vinylboronic ester 18 delivers the corresponding chiral alkylcopper

• species Int C or Int D, which undergoes an SN2'-like pathway with allylic phosphates 23 to generate the chiral products 43 or 44 along with the release of L*CuOR species. A σ-bond metathesis of this alkoxycopper species with HBpin and/or PMHS regenerates the L*CuH catalyst, completing the secondary

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• particularly useful and important tool in which azides and other dipolar species engage with reactive alkenes and alkynes on non-canonical amino acids [20]. Transition-metal-mediated processes, including metathesis reactions, aryl cross-coupling reactions, and conjugate addition reactions with dehydroalanine

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• containing a dimethylamino motif did not require an additional protecting group, ring closure was performed through alkene cross metathesis, which has been accomplished reliably and with good yields for other cryptophycins [11][26][27]. However, for the synthesis of a cryptophycin with a monomethylated amino

• group in unit B a suitable protecting group, i.e., allyloxycarbonyl (Alloc), must be used. Since the presence of this allylic double bond would most likely interfere with a clean reaction outcome after alkene cross metathesis, we decided for a more classical ring-closure strategy through

• obtained through Grubbs metathesis and subsequent acetonide cleavage in a superior yield of 76%. The finalising steps to obtain epoxides 26 and 2 (Scheme 3) were a diol–epoxide transformation [11][19][32], including firstly the formation of a cyclic orthoester, secondly the formation of a bromohydrin

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

• states. In this section, the document highlights applications of these complexes in reactions like ring-closing metathesis and polymerization, where red light’s deeper penetration enhances yields and efficiency, particularly for large-scale reactions. The second section broadens the focus to explore

• 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

• reduction potential to −0.97 V vs SCE, a value low enough to reduce the ruthenium complex 2, whose potential is estimated at −0.89 V vs SCE, thereby yielding 3, the active species for the metathesis reaction. The catalytic cycle is closed by the reduction of the resulting osmium(III) complex, regenerating

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• cycloadducts 29e and 31e in good yields (Scheme 12). Further derivatizations were also carried out: The treatment of 29e with SOCl2 led to interesting unsaturated derivative 32 in a 54% yield. The acetylation of 31e provided 33 in 76% yield. Next, an alkene metathesis of 33 with styrene led to product 34 in 72

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• aldehyde hydrazones using sodium sulfinates. These seminal works brought interesting proofs of concept for the synthesis of SR-containing hydrazones. Inspired by these previous works and taking benefit from our in-home expertise to forge N–SCF3 bond (after chlorination/anion metathesis with AgSCF3 from the

• morpholine hydrazone derived from 4-nitrobenzaldehyde was selected as a model substrate (Table 1). The latter was engaged in a two-step process: 1) halogenation to provide the corresponding N,N-hydrazonoyl bromide, which will then undergo an anion metathesis upon the addition of AgSCF3 to the reaction

• conducted in the presence of 1a in a THF/MeCN mixture (1:1) [75], but no product was detected (Scheme 4D). Based on these experiments and literature data [66], a two-step one-pot process was suggested based on 1) the bromination of the hydrazone 1 followed by 2) the anion metathesis in the presence of

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• assemblies, 2+-BF4− was further treated with NaPF6, LiB(C6F5)4, and NaPCCp for the ion-pair metathesis to afford ion pairs 2+-X− (X− = PF6−, B(C6F5)4−, and PCCp−) in 44–68% yields. The obtained ion pairs were characterized using 1H, 13C, and 19F nuclear magnetic resonance (NMR) and matrix-assisted laser

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• is produced in situ from the imidoyl chloride 9 [21]. The one-pot oxidation and ring-closure reaction [22][23] to iodoloisoxazolium(III) salt 7OTf and the salt metathesis with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBArF24) were then realized with 85% and 72% yield, respectively

• tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (−BArF24) was used instead of triflate [18]. Therefore, standard anion metathesis procedures were employed to prepare the salts 1BArF–4BArF (see Supporting Information File 1). Similarly to our previous report on this gold activation, the gold complex (PPh3

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -1,3-diamine 132 in 57% yield. The ring-closing metathesis of 121 (R1 = allyl, from Scheme 25) provided pure N-cyclohexenyl imine 135 in 98% yield. Asymmetric alkylation of imine-carbanion In 2023, a team of Huang and Yan [44] presented a novel approach towards synthetically important homoallylic α

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• ether 39, a ring-closing enyne metathesis (RCEYM) was initiated using the Grubbs second-generation catalyst (G-II) and high temperature to obtain the spiro 2,5-dihydrofuran derivative 40 in 76% yield. Additionally, when a dienophile such as N-phenylmaleimide was directly added to the same pot and

• being the major product (81% yield). Conversely, using 121b exclusively yielded the bis-acylated product 122b1 (59% yield), which was transformed into the mono-acylated compound 122b2 upon treatment with sodium methoxide. A final ring-closing metathesis (RCM) using a second-generation Grubbs catalyst (G

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• will then enable soft nucleophiles such as unadorned amides to readily participate in the ensuing olefin addition. In this regard, we wondered if the hypervalent iodine with difluoro ligands could undergo salt metathesis with lithium salts such as LiBF4 or LiPF6 to afford the more reactive cationic

• difluorinated iodotoluene B. Then, LiBF4 can perform a salt metathesis with B to produce LiF along with the active hypervalent iodoarene catalyst C. The activated hypervalent iodine catalyst C can coordinate to the alkene to form complex D. The nucleophilic oxygen of the amide will attack in the internal

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• pikromycin and the aglycones in this family, 10-deoxymethynolide (24) and norbonolide (25), using asymmetric aldol reaction, Yamaguchi esterification, and ring-closing metathesis as key steps [65][66]. Nevertheless, the inherent complexity of these natural products demands high step counts, leading to low

• , they established a preparative-scale approach toward the pikromycins family and their aglycones in 2013 [70]. The preparation of activated pentaketides (37) using asymmetric α-alkylation and cross metathesis as key reactions reduced the step counts from 14 to 11 steps. Replacing the extender unit from

• epoxidation with enzymatic macrocyclization in 2020 as shown in Scheme 8 [85]. According to their previous report [86], the production of fragments 61 was initiated by Evans’ asymmetric aldol and alcohol protection to generate 57. Six-step route transformations, including cross metathesis, afforded aldehyde