Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• with the steric effect of the tert-butyl group of the catalyst, is responsible for the high stereoselectivity of the reaction. Keywords: aromatic imine; asymmetric catalysis; Mannich reaction; noncovalent interactions; organocatalysis; Introduction The Mannich reaction, i.e., the addition of an

• ). This suggests that possibly the halogen bond plays a role in the emergence of the stereoselectivity of the reaction. The reaction with the similar quinidine derivative with reduced double bond (catalyst B) was slower and less selective affording the opposite enantiomer in low enantiomeric purity (14

• and I. Catalyst J lacking the iodophenyl core was much less reactive and 24 h were needed to reach full conversion of the starting imine. However, the stereoselectivity remains high and is comparable to that in the previous examples. Our results demonstrate that with tert-leucine-derived catalyst E

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• , isoquinoline, pyridine, and related substrates can now be reduced with high efficiency and stereoselectivity, providing efficient access to saturated and partially saturated architectures vital to synthetic chemistry. Furthermore, catalytic asymmetric aromatic hydrogenation has facilitated the asymmetric total

• building blocks used in natural product syntheses are often difficult to prepare or scale-up, constrained by subtle chemical reactivity, functional group compatibility, and control of stereoselectivity. Together, these factors continue to shape the pursuit of concise and practical synthetic routes to

• by substrate class (monocyclic vs fused; heterocycle vs carbocycle), all catalytic systems must still address the fundamental selectivity challenges inherent to arene reduction – chemo-, regio-, and stereoselectivity. Chemoselectivity becomes particularly demanding when reducible groups such as

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• stereoselectivity, exclusively yielding the Z-isomer. Nonan-2-one required activation with the stronger methanesulfonic acid and gave a 91:9 regioisomeric mixture of 91 to 92. 1-Tetralone provided the corresponding product 61 in only 7% yield; the acid additive was not specified in this case. The authors were

• aliphatic carbocations (Scheme 40A) [142]. Treatment of tert-butyl chloride (215) with alkyne 3 in the presence of ZnCl2 furnished alkenyl chlorides 155 and 9, along with considerable amounts of polymeric byproducts [93][143]. Compound 155 was obtained with excellent stereoselectivity (>98:2 E/Z

• alkenyl chloride product was favored by the utilization of a large excess (100 equivalents) of (E)-1,2-dichloroethylene in the presence of the Grela catalyst 290 [190]. Depending on the substrate, stereoselectivity and yields can vary significantly (Scheme 56). A subsequent study by Johnson confirmed

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• imino group in the E-isomer of adduct A leads to 4-thiocyano-2,5-dihydrofuran 3. Taking into account the NMR monitoring data, it can be assumed that the yield and ratio of products are influenced by the stereoselectivity of the reaction and the stability of salts 2 under reaction conditions. We also

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• the undesired α-alcohol. However, the stereoselectivity of the Grignard reaction could be reversed by previous complexation with the trimethylaluminum salt of BHT to give predominantly the desired β-alcohol. Protecting group manipulations at C20–OH and C18–OH were followed by treatment with TfOH to

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

• , thereby facilitating targeted molecular optimization. In 2016, the Inoue group accomplished the total synthesis of cinncassiol A (9) and B (7), cinnzeylanol (6), and 3-epi-ryanodol (5) through precisely controlled reactions with high stereoselectivity [15] (Scheme 6). Their approach allowed for the

• oxidation with freshly prepared trifluoroperacetic acid in n-pentane converted 111 to bis-epoxide 112 with excellent stereoselectivity and yield. Subjecting 112 to oxidation and organoselenium-mediated regioselective α,β-epoxy ketone opening, followed by intramolecular transesterification and elimination

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• reaction yielded the desired product at room temperature with high regioselectivity and stereoselectivity (E/Z ratio >99:1). Notably, when chiral catalyst (cat.1) was used, the reaction afforded the axially chiral product 9 in 43% yield with 84% ee. The proposed mechanism proceeds as follows. Catalyst cat

• products demonstrated complete E-stereoselectivity (E/Z ratio >20:1). Notably, under the same reaction conditions, aliphatic selenols remained unreactive. Density functional theory (DFT) calculations revealed that the rate-determining step involves the nucleophilic attack of the selenium anion in

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

• , and target specificity [86]. Impressive results were obtained by testing the photoinduced carboborative ring contraction reaction of terpenoids and steroids. The reactions proceeded with high regio- and stereoselectivity, leading to the formation of substituted cyclopentanes 162, 164a,b, 166, 168, 170

• formation of a mixture of ketone 194 and cyclic diene 195. Regio- and stereoselectivity was observed in the case of the epoxide 189. The cyclopentane derivative 194 was obtained stereoselectively and in high yield during the reaction with BF3·Et2O. An alternative example of the tandem epoxide rearrangement

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• -fumaramide showed stereoselectivity. Upon photoswitching to the cis isomer, the macrocycle moved to the thiodiglycolamide site, which disrupted its ability to catalyze the reaction, leading to the loss of stereoselectivity. This work represents the first evidence of a light-responsive interlocked catalyst

• capable of modulating reaction stereoselectivity. Hydrazone Hydrazones undergo trans–cis isomerization at the C=N bond when exposed to light, and in some instances, they can also undergo thermal isomerization (Figure 2) [69]. Although there are early reports of hydrazone derivatives in rotaxanes [70], the

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

• review, drawing on examples from recently reported natural product syntheses, elaborates on reaction mechanisms, factors governing regioselectivity and stereoselectivity, and the impact of substrate structures on reaction pathways. These reactions not only serve as robust tools for the streamlined

• , enabling the total synthesis of 13 via in situ intramolecular lactonization as a key step. Computational and experimental studies reveal that the regio- and stereoselectivity of the Norrish−Yang cyclization are governed by the influence of the methyl group at C10: (1) In terms of regioselectivity, the 1,3

• conformational preference at C8 that favors 1,5-HAT occurring at C9. (2) In terms of stereoselectivity, the steric hindrance between the spin center at C14 and the axial methyl group at C10 restricts the rotation around the C13–C14 bond, thereby enabling the diradical to undergo coupling stereoselectively. As a

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

• synthesis. Strategies for asymmetric radical reactions Stereoselectivity in radical reactions can be challenging to control. Many radicals are highly reactive, and radicals moreover have typically low inversion barriers, resulting in no permanent chirality at the radical center. Stereochemistry in radical

• catalysis affords the dual advantages of introducing stereochemical discrimination on both the radical and the trap via chiral ligands. Early research on parameters governing stereoselectivity in radical reactions was achieved with the help of radicals or radical traps appended with chiral auxiliaries. The

• reactions An emerging trend in the field of enantioselective radical transformations is the use of enzymatic catalysis to control absolute stereoselectivity. Some remarkable transformations have been demonstrated using this promising greener catalysis. This methodology has a bright future when used

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• 41 afforded the 1,3-cyclopentanedione derivative 42. Next, the baker′s yeast-catalyzed desymmetric enantioselective reduction of 42 gave the α-hydroxyketone 43 in satisfactory yield and excellent stereoselectivity and diastereoselectivity on a decagram scale [33][34]. Functional group modifications

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• product, which finally afforded the corresponding natural product gymnothelignan L after removal of the Bn protection (Scheme 6b). Interestingly, this transformation not only provided the expected skeleton, but also showed sole stereoselectivity in constructing the axially chiral diphenyl moiety. The

• cyclization to forge the spirocycle in one step represents a comparably more powerful method to rapidly generate complexity, since the de novo synthesis approach by Cuny and co-workers [42] has inevitably met with a lot of problems on stereoselectivity although they started the synthesis from a tricyclic

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• ; stereoselectivity; Introduction Photochemical reactions utilize light as a sustainable energy source and are considered to be ‘green’ reactions [1][2]. Organic chromophores absorb light, accessing higher-lying excited state(s) that exhibit distinct reactivities, leading to bond breaking and formation, irreversibly

• to experimentally measure the stereoselectivity of the reaction. In 1965, Crawford and co-workers experimentally found kinetic evidence for a 1,3-diradical from the thermal decomposition of 1 [56]. In 1963, Steel investigated the photolysis of diazabicyclo[2.1.1]hep-2-ene in solution, and the

• investigated the inversion stereoselectivity of housane formation using CASPT2(12,10)/6-31G(d)//CASSCF(12,10)/6-31G(d). They also used a single classical trajectory with UB3LYP/6-31G(d) to probe the ground-state relaxation dynamics immediately after the conical intersection. They found that the axial diazenyl

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• for stereoinduction by steric biasing. The stereocontrol connectivity index does not reflect the difficulty of inducing stereoselectivity, which can be subjective. In particular, the actual spatial distances between critical structural elements cannot be measured simply by using bond connectivity

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

• enantioselective desymmetrization of prochiral 1,3-diols within complex structures can be realized using organometallic catalysts composed of copper or zinc salts and different types of chiral ligands. In general, the ability to control the stereoselectivity of the product by using the enantiomer of the ligand in

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• products with complete stereoselectivity. Substrates bearing electron-donating or electron-withdrawing groups on the aromatic rings provided good to excellent yields, indicating that both types of substituents are well tolerated under the reaction conditions. Although modest yields were obtained under flow

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

• effects of the CPAs, which establish a chiral microenvironment within the chiral scaffold that governs the stereoselectivity of asymmetric reactions. Chiral molecules, characterized as three-dimensional structures that are nonsuperimposable with their mirror image, have significant applications in

• stereoselectivity for the more sterically demanding aza[5]helicene 3c and aza[7]helicenes 3d–f. Furthermore, the authors expanded this methodology to a double Fischer indolization reaction between hydrazine 1i and ketone 2i, which yielded diaza[8]helicene 4 with moderate yield and high enantioselectivity after

• diverse catalytic abilities, precise stereoselectivity control and mild reaction conditions. In this Review, we systematically summarized the advancements in the CPA-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules. Various CPA-catalyzed reactions, such

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• advances in 1,1′-glycosylation and provides an overview of selected glycosylation strategies, including those aimed at forming α,β-, β,β-, and α,α-1,1′-glycosidic linkages. Particular emphasis is placed on the challenges of achieving stereoselectivity with lactol glycosyl acceptors, which commonly exist as

• traditionally presents challenges such as modest stereoselectivity, the formation of various diastereomeric by-products and moderate yields. The configuration of the glycosidic linkage (ββ, αα or βα) is the most important factor in choosing an appropriate glycosylation approach, alongside the specific

• '-glycosylation, alongside a retrospective on specific glycosylation approaches, focusing particularly on the construction of α,β- and β,β-1,1'-glycosidic bonds in pyranoses. Special emphasis is placed on the challenges of controlling stereoselectivity on the side of the lactol glycosyl acceptor, as lactols

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

• 72% yield and excellent regio- and stereoselectivity. Regarding the acceptor, compound 6 harbored two free alcohol groups at the C3 and C2 positions. Since the C3 alcohol group is less sterically hindered and exhibits better nucleophilicity, the glycosidic bond formed regioselectively at the C3

• same reaction mixture, in situ activation of disaccharide donor 8 and acceptor 9 using TolSCl/AgOTf reagent combination was introduced. This two-step, one-pot glycosylation gave a 42% yield of disaccharide 10, maintaining good β-stereoselectivity at the galactosyl linkage (α/β = 1:5.8). The 2

• 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

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• substitution pattern on the regioselectivity and stereoselectivity of the reactions. A Review article by Papis and co-workers discusses various copper(II) triflate-catalyzed multicomponent reaction types [2]. Therein, the synthesis of cyclic and acyclic compounds, as well as three-component and four-component

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

• substrate scope revealed that the reaction stereoselectivity is highly dependent on the structure of the ketoester component and tends to be unpredictable. 1.3.2 Formal cycloadditions: These stepwise processes typically take place between an enolate or enol ether and a carbonyl under Lewis acid or base

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

• stereoselectivity. The authors emphasized that, as the alkene moiety in 54 was in a terminal position, the stereoselectivity of the products was determined solely by the chiral environment of the catalysts. The application of this method to construct the C3–C11 fragment 60 of borrelidin is summarized in Scheme 8

• CuBr·SMe2, facilitating the formation of deoxypropionate 125 in 80% yield with excellent regioselectivity (>99:1) and stereoselectivity (99:1 dr). Ozonolysis of 125 followed by reductive work up with NaBH4 afforded alcohol 126 in 92% yield. At this stage, the authors explored an alternative procedure for

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

• tendencies of electronic effect on the yield and stereoselectivity were observed as those in the reactions involving 1a, but the enantioselectivities were generally higher than those in reactions involving 1a. Electron-rich benzaldehydes 2c and 2d and sterically bulky benzaldehydes 2i and 2k generated the

• of the catalyst for the next catalytic cycle. The electron-deficient aromatic aldehydes exhibit excellent stereoselectivity due to the π-stacking interaction between their aryl group and the electron-rich malonate group. Similar π-stacking interaction-controlled stereoselectivities were observed in

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

• advancements in this area have recently been demonstrated to access conjugated alkenes, particularly cinnamic acid derivatives, with high stereoselectivity. For instance, Reeves and co-workers (2023) performed a Horner–Wadsworth–Emmons reaction of triethyl 2-fluoro-2-phosphonoacetate (390) and aldehydes to

• and using ylide 397 altered the stereoselectivity to E-isomeric products 400 and 401 [144]. Wu and co-workers (2020) employed Pd to mediate the cross-coupling reaction of sulfoxonium ylide 402 and benzyl bromides to give the corresponding (Z)-ethyl cinnamates 403–406 in good yields via carbene