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

• hydroxy group, affording aldehyde 238 in 78% yield with >10:1 dr. The high diastereoselectivity observed in the oxidation of the 1,3-diol indicated that the complex structure of the substrate could provide an environment of desymmetrization. The stereospecific cyclization of 238 was performed with

• , compound 266 was prepared in a seven-step sequence. Then, the cascade cyclization was accomplished by treatment with NaOMe in MeOH, followed by H2O, affording compound 267 in excellent yield and diastereoselectivity. A subsequent three-step sequence gave diol 268. Under DDQ and AcOH conditions, the

• diastereoselectivity. Compound 288 was then treated with Co(acac)2, 1,1,3,3-tetramethyldisiloxane (TMDSO), and O2 in degassed iPrOH, undergoing a hydrogen-atom-transfer (HAT)-initiated redox radical cascade to give pentacyclic alcohol 289, which was converted to C18/19 diol 290 in two steps. To differentiate the two

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

• diastereoselectivity. Previously, they have been challenging to access in an asymmetric one-step reaction. A range of paracyclophanes with diverse substitutions, including aryl, heteroaryl, alkynyl and bromo substitutions, along with a varying length of the ansa chain, were found to be amenable to this method

• with poor diastereoselectivity while maintaining high enantioselectivity for both diastereomers (see 76d–g). Furthermore, the authors have investigated the asymmetric condensation using other seven-membered cyclic ketones (see 77a) as well as the coupling with alkylhydroxylamine (see 77b

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

• , pyruvate ketals are attached to the O4 and O6 positions of galactose, incorporating a negatively charged carboxyl group. The diastereoselectivity and negative charge of pyruvate ketals have a key role in their biological interaction, such as influencing immunological specificity and patterns of

• was significantly faster, and the starting material was completely consumed within 2 h, followed by deacetylation to yield the desired product 6 in 51% (Table 1, entry 3). The use of this more reactive reagent maintained high R-diastereoselectivity. It is hypothesized that this reaction will yield a

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

• ). However, the diastereoselectivity is modest (1.7:1), likely resulting from insufficient chiral induction during the indolinone-forming step. Moving forward, this strategy was applied in the construction of axial chirality by the same group. In 2021, they reported a Pd(OAc)2/L2-catalyzed imidoylative

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• -catalyzed reaction proceeds with low diastereoselectivity. The significant difference in selectivity can be explained by the fact that, in contrast to the Ni(II)-catalyzed reaction depicted in Scheme 3, the copper(I) catalysis involves the coordination by the metal of both reaction partners, and the

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• conditions, compound 15 and its diastereomer were obtained in a total yield of 90% at a ratio of 1:0.7. To improve the diastereoselectivity, we examined other reduction conditions and found that ʟ-Selectride afforded compound 15 in 90% yield with a dr of 9:1. Upon desilylation with TBAF, compound 15 was

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

• diastereomeric ratios favouring the trans-isomer, however, a reversed diastereoselectivity was observed for ortho-substituted aryls due to steric factors. The investigation of the substrate scope revealed that while the reaction shuts down in the absence of the trifluoromethyl group in the ketone component, it

• amidine base catalysis (Scheme 25b) [69]. Although this methodology employs equimolar catalyst loadings, the products 100 are obtained with complete diastereoselectivity and mostly in moderate to good yields. As for the mechanism, it is assumed to be analogous to the NHC-variant. Four years later, Somappa

• halogens, nitriles, alkenes and heteroaryls. On the other hand, this methodology suffers from relatively low diastereoselectivity as the dr lies between 1:1 and 2:1. DFT calculations suggested the reaction proceeds through nitrogen elimination, oxonium ylide 119 formation, homolytic cleavage and radical

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

• functionality of 87 was reduced to the corresponding primary alcohol with DIBAL-H and converted to the iodide derivative using Ph3P/I2/imidazole reagents. The resulting iodide was treated with lithiated (R,R)-91 to afford compound 86 in a 76% yield with excellent diastereoselectivity (>99:1 dr). Finally

• demonstrated when compound 100 was treated with MeMgBr/CuBr and either 94 or ent-94, affording 101a and 101b, respectively, with high yield and exclusive diastereoselectivity. Compound 101a, featuring the relevant stereochemistry of borrelidin at the C4, C6, C8, and C10, underwent Baeyer–Villiger oxidation

• hydrogenation of 104, employing (R)-[(RuCl(Tol-BINAP))2(μ-Cl)3[NH2Me2], yielded the product in 90% yield with nearly complete diastereoselectivity (de >99%). Finally, the secondary alcohol was protected as a TBS ether, and the ester group was hydrolyzed to deliver Ōmura’s C1–C11 fragment 61 in 85% yield. The

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• to investigate how the configuration of the stereocenter in C2 position influences diastereoselectivity. In the first approach, NaBH3CN was used under acidic conditions to reduce the acyliminium intermediate formed from the N-acyl enamine upon protonation at C5, while in the second approach

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• 32% when 2,6-lutidine (0.02 mmol) was added (Table 1, entry 3). When pre-dried Sc(OTf)3 was used instead of commercially available one, the reaction generated the desired product 3aa in 39% yield with 70% ee and >20:1 diastereoselectivity (Table 1, entry 4). The product 3aa was identified as diethyl

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

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

• aldol condensation of 5 provided the tetracyclic α,β-unsaturated enone 6 in 57% yield. Subsequent catalytic hydrogenation using Pd/C conditions delivered the hydrogen to the alkene from the less hindered face, producing ketone 7 with high diastereoselectivity. Final reduction of both the amide and

• was utilized to transform enamine 18 and propargyl ester 19 into 1-azaspiro[4.4]nonane 20 with high diastereoselectivity. Notably, the combination of an N-heterocyclic carbene gold catalyst and a silver salt AgSbF6 was found to be essential in guaranteeing the reactivity of the alkyne partner

• responsible for the excellent diastereoselectivity observed in the second cyclization process. In their later studies, the authors also found cyclohexanone-derived tertiary enamides to be viable substrates for the polycyclization [32], affording erythrinane core skeletons in high yields. However, in these

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

• Abstract We present the first examples of alkene amino-sulfonoxylation reactions that leverage the unique reactivity of carbamate tethered N-alkoxy nitrenium ions. In almost all cases examined, the reactions deliver product with exquisite regioselectivity and diastereoselectivity. The protocols followed

• diastereoselectivity (Table 4, entry 1). A urea substrate also furnished the expected product in a good yield and with high diastereoselectivity (Table 4, entry 3). With tri-substituted allylic carbamate 35, some amount of expected mesyloxylated product 36 did form, but there was also an isolable amount of a terminal

• terminal alkene substrate 60, unproductive decomposition of starting material was again observed. Given the highly predictable diastereoselectivity of this transformation and by analogy to prior art [4][6], we hypothesize that the reaction proceeds through the formation of a transient nitrenium species

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

• features of the starting material. By exploiting preorganization, steric effects, or directing groups within the substrate, chemists can achieve high levels of regioselectivity, diastereoselectivity, and enantioselectivity without relying on external catalysts or additives. This approach has been

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

• are shown to undergo a rare dimerization process when reacted with bis(pinacolato)diboron under copper catalysis. The reaction provides densely functionalized products with excellent levels of chemo-, regio-, and diastereoselectivity. This high degree of functionalization makes these products

• (1) and B2pin2 (Table 1). By using NaOt-Bu as base and toluene as solvent, the Cu/SIMes catalyst provided compound 2 as single reaction product, albeit in low yield and with low diastereoselectivity (Table 1, entry 1). Lowering the amount of B2pin2 to 1 equivalent was found to be beneficial (Table 1

• the base metal cation. Gratifyingly, we observed that the use of LiOt-Bu led to the formation of product 2 as a single diastereomer (Table 1, entry 5). A slightly lower diastereoselectivity was observed when KOt-Bu was used, which also gave rise to 2 in diminished yield (Table 1, entry 6). The nature

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• (65 kcal/mol) and substrate. The use of xanthone demonstrated clean translation to product favouring syn diastereoselectivity [61][62] (Table 2, entry 4), with additional catalyst increasing yield during the 16 h reaction time (Table 2, entry 5). With a general set of reaction conditions for the [2

• . Access to vicinal boron scaffolds 4f and 4g provided conclusive evidence that sensitization of alkenylboronic esters is achievable using xanthone, with in situ oxidation enabling direct access to otherwise challenging to synthesize cyclobutyldiols. The lower observed diastereoselectivity may reflect

• , bottom). Despite the additional substituent, the reaction was tolerated, albeit with decreased diastereoselectivity in comparison to previous alkenylboronic ester examples 4b–d. To demonstrate the synthetic utility of the generated small 3D fragments and complement existing [2 + 2] strategies via direct

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

• remains a formidable challenge, primarily due to the inherent ring strain and the difficulties associated with achieving high diastereoselectivity during cyclization [4]. Recently, Chen and co-workers developed a chiral phosphoric acid (CPA)-catalyzed multicomponent reaction of anilines, aldehydes, and

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• ) complex with the corresponding fluorinated alkyl iodide. The aryl moiety of the Ni(II) complex blocks the top face of the complex, ensuring the high diastereoselectivity of this transformation. In principle, synthesis on a gram-scale permits the study of highly fluorinated systems. Recently, we introduced

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

• 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

• substitution of vinylboronic esters. (a) Generation of chiral copper species via enantioselective CuH addition to vinylBpin. (b) Regarding the origin of diastereoselectivity in CuH-catalyzed enantioselective allylic substitution. CuH-catalyzed enantioselective allylic substitution of 1‐trifluoromethylalkenes

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• monohydrolysis under basic conditions. The electrolysis proceeds in an undivided cell under galvanostatic control using low-cost graphite or stainless-steel electrodes, and the protocol was easily upscaled. Notably, an excellent diastereoselectivity (97:3 dr) could be achieved in the cyclization of a tethered

• meantime, an excellent diastereoselectivity (97:3 dr) was achieved in the decarboxylative cyclization of N-mesylamide 9n possessing an S stereogenic center in the α-position to the nitrogen. Unfortunately, the configuration of the newly formed quaternary stereogenic center in 6n could not be established by

• tethered nitrogen nucleophiles such as sulfonamides, carbamates, and benzamide. The decarboxylative cyclization of a stereogenic center-containing sulfonamide proceeds with excellent diastereoselectivity (97:3 dr). The N-protected 2-aminoproline derivatives can be incorporated into dipeptides by an ester

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

• equivalent of 7a and 5.0 equivalents of 16a in the presence of stoichiometric potassium carbonate and 1.0 mol % of 9. When bromonium salt 9a was applied to the reaction, the desired product was obtained in 83% yield with 77% ee but almost no diastereoselectivity. The iodonium salt 9b also worked well and the

• found to be optimal in enantioselectivity, and iodonium salt 9b was superior in terms of diastereoselectivity. These results can be explained by the strength of halogen bonding: generally, iodo-substituted compounds form stronger halogen bonding with Lewis bases than chloro-substituted ones [1]. Notably

• formed 17g in good yield and diastereoselectivity with decreased enantioselectivity, likely due to electronic effects. 6-Bromo- and 7-chloro-substituted substrates also provided 17h and 17i in good yields with moderate to good stereoselectivities. Next, Cbz-protected imine 7j was employed in the present

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

• diastereoselectivity (up to 7:1). Keywords: alcohols; diastereoselectivity; nitrogen heterocycles; pyrazoles; vinylogous reaction; Introduction Vinylogy refers to the transmission of electronic effects through a conjugated π-system, enabling the extension of a functional group's nucleophilic or electrophilic

• (Table 1). First, we tried several solvents (dichloromethane, toluene and dichloroethane, entries 1–3 in Table 1) at room temperature, obtaining product 5aaa in yields around 50% with high diastereoselectivity (up to 6:1) after several days. Increasing the temperature to 50 °C (Table 1, entries 4 and 5

• dichloroethane, chloroform or ethyl acetate gave lower yields but similar diastereoselectivity. More polar solvents such THF and CH3CN afforded the corresponding alcohol 5aaa with lower diastereoselectivity. When acetone was used as solvent, product 5aaa was not detected in the 1H NMR of crude reaction mixture

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

• -Michael (ReM) reaction occurs, its enantio- and diastereoselectivity, and the influence of different experimental parameters on its scope and stereoselectivity. The reaction was studied on a 1:2 mixture of the racemic diastereoisomers syn-1 and anti-1 (prepared according to our previous protocol) [25

• reactions and their impact on the enantioselectivity and diastereoselectivity of the products. The results show that Michael adducts can evolve from enantioenriched mixtures to racemic ones in the crude reaction while in contact with the chiral organocatalyst. Conclusion The first example of the

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• . Diverse functionalized 3-substituted oxindole derivatives were successfully prepared in satisfactory yields and with high diastereoselectivity. In addition, the base-promoted dimerization of MBH carbonates of isatin afforded the ethylene-bridged bis(3-methylene)oxindole derivatives with nearly 4:1

• investigated nucleophilic substitution reactions of various N- and P-containing nucleophiles to MBH carbonates of isatins. It is interesting to find that diverse functionalized 3-substituted oxindole derivatives were successfully prepared in satisfactory yields and with high diastereoselectivity. In addition

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

• and isatin-derived 3-indolylmethanols 135. Over 90% diastereoselectivity, mostly very good yields, and consistently high enantioselectivities were reported. Testing the practicality of the protocol, the gram-scale experiment provided representative product 136 in 93% yield and an excellent