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

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

• -protected Michael acceptor, derived from proline, allowed for preparation of compound 27 with a 35% yield in 4 hours without control of diastereoselectivity (dr = 1:1). Finally, to prove that the optimized reaction also works at a larger scale, the model reaction was carried out on a 2.2 mmol scale (Figure

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

• Michael addition product was obtained with low diastereoselectivity. The mechanism is described in Scheme 4: the bifunctional squaramide activates the azadiene through hydrogen bonding while the malononitrile is deprotonated by the tertiary amine present in the backbone of the catalyst, establishing

• with high diastereoselectivity (Scheme 5). In 2019, Shi and co-workers established a guanidine-catalyzed enantioselective (4 + 1) cyclization of benzofuran-derived azadienes 11 with 3-chlorooxindoles 18 [28]. This work provides a useful strategy for the synthesis of chiral spirooxindole derivatives 19

• product 24f. To show the applicability of this novel methodology, a gram-scale reaction was carried out obtaining comparable results as in a small scale. Besides, an α-bromination of the product 24f was performed obtaining 25 in 73% yield and complete diastereoselectivity (Scheme 9). In 2021, Zhao and co

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• -carboxamide-1,4-benzodiazepin-5-ones when enantiopure (S)-(−)-α-methylbenzylamine and arylglyoxals were used. Thus, a reversal of diastereoselectivity was observed depending on the cyclization methodology employed, the reduction of a nitro group or the Staudinger/aza-Wittig on azide derivatives. This

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

• cyclisation of alkenyl N-tosylamides using BF3-activated aryl iodane(III) carboxylates to create 3-fluoropiperidines [35]. The challenges faced relate to selectivity due to competing carboxyaminations (18, 18’), rather than fluoroamination (17, 17’), and difficulties in controlling the diastereoselectivity

• aminofluorination using BF3·Et2O with a chiral aryliodide 16 catalyst (Scheme 20) [44]. The study successfully obtained various chiral fluorinated oxazine products 38 with high enantioselectivity (up to >99% ee) and diastereoselectivity (up to >20:1 dr). Control experiments showed that using Py·9HF or Et3N·3HF as

• HVI reagent has also shown to dictate the regioselectivity of the reaction. Future research efforts should focus on further developing access to new heterocycles, as well as designing better systems to incorporate high levels of diastereoselectivity and enantioselectivity into chiral halogenated

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• to be the determining step for the enantioselectivity, while the diastereoselectivity is mainly induced by the chiral alkylated naphthol intermediate in the second annulation step (Scheme 46). Xu et al. [80] realized asymmetric [4 + 1] cyclization of yne-allylic esters with pyrazolones. This

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• oxidation strategy to obtain α-chlorosulfoxides from sulfides using hydrochloric acid as a bifunctional reagent [22]. This strategy accommodates a broad range of substrates and offers high diastereoselectivity and regioselectivity. Several LSF modifications of amino acids and pharmaceutical derivatives

• . Additionally, pyrrolidine, anazepane, and morpholine scaffolds successfully underwent the reaction. Another notable feature of this method is its high diastereoselectivity. All products were ultimately obtained as p-toluenesulfonic acid salts (Scheme 27). In 2021, Zhang et al. developed an electrochemical

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• 8d exhibited an enhancement in reaction diastereoselectivity, resulting in the isolation of product 11d with a dr of 6.7:1 in favor of the trans-diastereoisomer. Remarkably, the formation of a fully substituted quaternary center was possible, as observed for the product 11g, where the trans

• the diastereoselectivity of the nucleophilic attack of the β-lactam on the radical cationic intermediate was influenced by stereoelectronic factors. Compounds unsubstituted at position C-3 of the β-lactam ring, 11d–h, showed modest stereoselectivity with a higher dr (6.7:1) for compound 11d, which has

• an electron-donating methoxy group on the phenyl substituent. Derivatives with a 3-OTBS side chain, 12c–e, displayed moderate diastereoselectivity, except for the higher diastereoselectivity achieved for 12f (dr 20:1), probably due to steric effects, albeit at the expense of a reduced isolated yield

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• indicated DMSO as the best for the attainment of high yields and diastereoselectivity (entries 1–5 vs 6 in Table 4), we further examined bases in this solvent to find out that t-BuOK behaved nicely, and the reaction of 2b with 2.0 equiv of diethyl malonate for 0.5 h at room temperature furnished 93% yield