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

• , and introduction of an isopropenyl group afforded compound 75. Subsequent protection of the vicinal diol as a boronic ester and diastereoselective reduction of the C3 carbonyl group yielded compound 76. Esterification with acylating reagent 77 under basic conditions, followed by boronic ester removal

• diastereoselective reduction of the C3 ketone, the acyl pyrrole group was introduced to yield 81. During acyl pyrrole installation, excess KHMDS enolized the lactone to suppress lactone-C3 hydroxy transesterification. However, α-chlorination of the ester carbonyl was unavoidable. Finally, reductive dechlorination

• , thus establishing the core C and D rings. Base-mediated equilibration fully converted 93 into lactone 94. Finally, selective hydroxy protection in 94, diastereoselective introduction of the C10 secondary alcohol, and global deprotection completed the total synthesis of anhydroryanodol (10). Application

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

• rearrangement to produce lactone 58 with a yield of 78%. The last stage of the synthesis proceeds through a chemo- and diastereoselective reduction of lactone 58, containing the desired trans-fused bicyclo[3.3.0]octane ring system, leading to the target 4β-acetoxyprobotryane-9β,15α-diol (52). An alternative

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• , a highly diastereoselective method for the synthesis of dihydrospiro[indoline-3,2'-pyrrole]-2-ones has been developed (Scheme 1, path a) [7]. This transformation proceeds via a Lewis acid-mediated conjugate addition of vinyl azides to electron-deficient alkenes, followed by denitrogenative

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

• by the Yang group [22]. Installation of the hydroxymethyl group in 4 was achieved through sequential formylation and reduction. Compound 4 then underwent a one-pot, substrate-controlled diastereoselective Johnson−Claisen rearrangement/acetylation to install ester 5. Treating 5 with m-CPBA (meta

• , followed by diastereoselective α-alkylation, produced 38. A Wittig reaction and subsequent deketalization converted the ketone in 38 to the terminal alkene 39, allowing for subsequent sequential chemoselective hydrogenations: first, hydrogenation of the exo-olefin using Wilkinson’s catalyst proceeded with

• -obscurine (83) as a late-stage common intermediate. Compound 83 was readily accessible via previously reported protocols [40], which featured a diastereoselective formal [3 + 3] cycloaddition between 76 and 81 as the key step. This cycloaddition constructs the three contiguous stereocenters and two C–C

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• photoenzymatic transformation developed by the Hyster group, α-chloroamides were converted to enantioenriched 5-, 6-, 7-, and 8-membered lactams through an enantioselective radical cyclization followed by a diastereoselective HAT, producing contiguous stereocenters [75]. In the subsequent year, the same group

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

• reaction involves the enantioselective organocatalyzed transfer of boronic acid to HFO followed by an intramolecular diastereoselective Passerini-type reaction. Varying the boronic acid enabled to reach high yields (Scheme 39) [124]. The tautomeric transformation of HFO to cis-β-formylacrylic acid was

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• -workers [21], its synthesis has attracted attention of the synthetic community. The group of Snider [47], Evano [48][49], and Papeo [50] reported several elegant highly enantio- and diastereoselective total syntheses of this alkaloid from ᴅ-tryptophan. With our longstanding interest in the efficient total

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

• The retrosynthetic analysis of tricyclic-PGDM methyl ester 4 is shown in Scheme 2. We expected to derive 4 from tricyclic substrate 12 via a side-chain installation at C8 [22]. The spiroketal moiety in compound 12 could be obtained from compound 13 via a diastereoselective spiroketalization dictated

• 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

• 4 was expected to be derived from tricyclic substrate 26 via a Z-selective cross-metathesis [9]. The allyl group in compound 26 could be installed in β-keto ester 21 via sequential transesterification [33] and palladium-catalyzed decarboxylative allylation [32]. The regio- and diastereoselective

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

• , ligand 205a proved to be suitable for 2-ethylpropane-1,3-diol (204). A three-step sequence then furnished enone 207, which underwent diastereoselective aldol reaction with fragment 208 to give compound 209. Alkyne 210, prepared from 209 in six steps, underwent addition with fragment 211 to yield compound

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

• reactions. Out of these, the aza-Diels–Alder reaction with TsNCO was successful, leading to a highly diastereoselective formation of an oxazolo[3,2-c]pyrimidine derivative. Keywords: aza-Diels–Alder reaction; electrosynthesis; furfural; valinol; vinyloxazoline; Introduction The utilization of biomass as

• to form oxazolo[3,2-c]pyrimidine derivative 7 (Scheme 7). The highly diastereoselective formation of product 7 can be explained based on the theoretical calculations by Elliott et al. of aza-Diels–Alder reaction of vinyloxazoline with TsNCO [19]. According to their investigations, the aza-nucleophile

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• promising regio- and stereoselectivity. Detailed characterization using NMR and X-ray methods clarified the diastereoselective structure of the pyruvate ketals, enabling the successful synthesis of oligosaccharides containing pyruvate ketal groups. Pyruvylated galactose on bacterial polysaccharides PS A1 (1

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

Correction: Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha,
• Lakshminarayana Satham and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2025, 21, 1170–1170, doi:10.3762/bjoc.21.93

• Deepa Nair Abhishek Tiwari Banamali Laha Lakshminarayana Satham Irishi N. N. Namboothiri Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India 10.3762/bjoc.21.93 Keywords: arylidenemalonates; curcumins; cyclohexanones; diastereoselective synthesis; Michael

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

• presence of pivaloyl chloride, triethylamine, and lithium chloride to produce compound 71 in 86% yield. Diastereoselective methylation of 71 was achieved by treating it with NaHMDS at low temperature, followed by the addition of methyl iodide, resulting in a diastereomeric ratio greater than 98:2

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

• , the terminal alkene remains intact during this process, and the initial protonation proceeds with full stereocontrol, rendering this transformation both highly chemo- and diastereoselective. From the cyclization result, it is presumed that the higher nucleophilicity of the alkyne functionality over

• total synthesis of cephalotaxine. Similarly, diastereoselective reduction of 25 with KBH4 followed by alane reduction provided another alkaloid cephalezomine H. Collective total syntheses of Cephalotaxus alkaloids The cyclopentane ring in most Cephalotaxus alkaloids is characterized by the highest

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

• ring was opened in a diastereoselective (SN2 type) and exo-selective manner by a trifluoroacetate anion. The trifluoroacetate anion was conveniently derived from (bis(trifluoroacetoxy)iodo)benzene (PIFA), which was used as the stoichiometric oxidant in the reaction. Overall, this amounted to a highly

• regioselective, diastereoselective, and metal-free protocol for alkene amino-hydroxylation, which compared favorably to prior art in this area [25][26][27][28][29][30][31][32]. Naturally, we wondered if other O-nucleophiles were competent in the ring-opening of the aziridinium intermediate. Indeed, almost all

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• from α-iodoenone 13. Our synthesis began with the preparation of α-iodoenone 13 (Scheme 2). The α-monomethylation of cyclohexenone 15 was efficiently carried out with LDA, HMPA, and MeI [37], producing enone 16 in 78% yield. Subsequently, a diastereoselective aldol reaction between 16 and 3-furaldehyde

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

• ). We have studied this reaction and now report a catalytic methodology for the diastereoselective synthesis of these dimeric structures. The high degree of functionalization present in these molecules, which feature two ester groups, an aliphatic gem-dichloride and a dichloroalkene unit, offers ample

• opportunities for further functionalization. This is illustrated by their chemo- and diastereoselective conversion into densely functionalized cyclopropanes (Scheme 1c). Results and Discussion Based on our preliminary result, we started our study by exploring the reaction between ethyl 4,4-dichloro-2-butenoate

• mechanism for the copper-catalyzed diastereoselective dimerization of 4,4-dichoro-2-butenoic acid derivatives (Scheme 4). Initially, the LCu–pin complex generated through reaction between LCu–Ot-Bu and B2pin2 undergoes coordination and regioselective insertion into 1 giving rise to β-borylated organocopper

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

• azetidinones, enabling the efficient and enantioselective synthesis of tetrahydroquinoline-fused azetidines with three contiguous stereocenters in a single step [23]. Later, Tanaka, Nagashima, and their co-workers established a chemo-, regio-, and diastereoselective dearomative transformation of quinolines

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

• approach focused on the diastereoselective formation of homoallylic boronic esters 36 through a carefully controlled sequence of hydrocupration and allylic substitution [39]. Through optimization studies, Yun found that CuCl with the Walphos ligand (L2) in Et2O provided optimal results, delivering the

• traditional crotyl addition to acetaldehyde. This methodology represents the first example of highly enantio- and diastereoselective copper-catalyzed allylic substitution that controls vicinal stereogenic centers. DFT calculations revealed that the high enantioselectivity (98:2 er) originates from a face

• with olefins bearing electronic directing groups (such as aryl, boryl, or trifluoromethyl substituents) that guide regioselective hydrocupration, unactivated alkyl-substituted alkenes pose a persistent challenge. The recent breakthrough in CuH-catalyzed enantioselective and diastereoselective allylic

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

• enantio- and diastereoselective Mannich reaction of α-cyanoesters with aldimines catalyzed by chiral amines, which provided β-amino cyanoesters in excellent yield and diastereoselectivities with up to 98% ee (Figure 2a) [41]. The Mannich reaction has been also applied in the construction of contiguous

• chiral halonium salt. Conclusion In conclusion, the enantio- and diastereoselective Mannich reaction was developed by chiral halonium salt catalysis, which provided the corresponding products with contiguous chiral tetrasubstituted carbon centers in excellent yields with up to 86% ee using only 1 mol

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

• functionalization of 5-aminopyrazoles [26], we decided to study 4-alkenyl-5-aminopyrazoles as nucleophiles in the vinylogous addition reaction to electrophiles. Herein, we report the regioselective and diastereoselective functionalization of 4-cyclohexenyl-5-aminopyrazoles using alkyl trifluoropyruvates [27][28][29

• 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

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• to enamine E, which epimerizes at C-4 and, after hydrolysis, provides the adduct syn-(3R,4R)-1 with an initial er of 4:96. This diastereoselective epimerization phenomenon promoted by an organocatalyst has not been previously described. The study emphasizes the reversibility of some organocatalyzed

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• (cis/trans) determined by 19F NMR analysis. Kitamura’s synthesis of 3-fluoropyrrolidines. Values in parentheses represent the cis:trans ratio. Jacobsen’s enantio- and diastereoselective protocol for the synthesis of syn-β-fluoroaziridines 15. Different HVI reagents lead to different