Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• -functionalization, where a bulkier handle provides the required enantiomerization barrier to screw helical chirality (Figure 1C and D). A straight forward preparation of various carbohelicenes via an organocatalytic enantioselective hydroamination reaction of polyaromatic phenols with diazodicarboxamide derivatives

• also be applicable to other polyaromatic frameworks beyond specific helicenes for the construction of helically chiral structures. Outlook Despite its potential, this strategy has faced significant challenges in the context of catalytic enantioselective synthesis of functionalized helicenes and their

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• versatile intermediates for enantioselective S–C bond formation under mild and metal-free conditions. Keywords: asymmetric synthesis; late-stage functionalization; selective oxidation; sulfenamides; sulfinimidate esters; Introduction Sulfur is a privileged heteroatom in organic chemistry, celebrated for

• previously disclosed a PIDA-mediated oxidative strategy for alcohol incorporation via activation of the S–NH bond (Scheme 1a) [14]. More recently, Wu and co-workers advanced the field by developing a dynamic kinetic resolution protocol for the enantioselective synthesis of sulfinimidate esters from racemic

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

• product in a slightly less enantioselective way (71% ee). When comparing the halogen bond donor properties of tetrafluoroiodophenyl and iodophenyl moieties, the latter is weaker as it is less electron-withdrawing. However, there is a very small difference between reactivity and selectivity for catalysts E

• reactive under standard conditions than dimethyl malonate and dibenzyl malonate gave the product with high yield, but the selectivity dropped significantly (compound 3i). Conclusion In conclusion, we have designed a new catalyst enabling highly enantioselective Mannich reactions of aromatic imines

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

• , Aggarwal and co-workers reported a concise and enantioselective synthesis of (−)-finerenone via an asymmetric hydrogen atom transfer (HAT) strategy, completing the total synthesis in just six steps with high efficiency and stereoselectivity [94]. Starting from the 2-pyridone derivative 178, the authors

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

• the alkenyl chloride motif. Scheme 64, depicts representative examples by Boger [200], Taber [201], and Morken [202]. In 2012, Feringa and co-workers reported the first enantioselective allylic substitution of allylic gem-dichlorides with alkyl Grignard reagents (Scheme 65A) [203]. The reaction

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

• enantiomeric excess of 92%. This asymmetric hydrogenation included a novel iridium catalyst featuring a chiral SpiroBAP (spiro bidentate aminophosphorane) ligand, which has been developed previously by this group and was now successfully applied in this synthesis [36]. A silver-catalyzed, enantioselective

• sequence was an asymmetric hydrogenation developed by the same group and an enantioselective vinylogous Mannich reaction. For a more detailed explanation of the synthesis of these fragments, the reader is referred to the synthesis of cyclopamine (6) in the previous paragraph (Scheme 10). Convergent

• alkyne fragment 116 (see Scheme 33). The synthesis of diyne fragment 112 commenced with an organocatalytic, enantioselective Diels–Alder reaction between siloxydiene 108 (synthesized in one step from ethyl vinyl ketone) and commercially available dienophile 109 using the proline-derived Hayashi ligand

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

• enantioselective synthesis of atropisomers, and significant progress has been made in recent years. However, selenium-containing atropisomers have long remained underexplored as synthetic targets, and only in recent years have they begun to attract increasing attention from the community. Recently, several

• currently lacking. This review aims to provide an overview of recent developments in the catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formation. We hope this review will serve as a valuable reference for researchers interested in further exploring this area

• axially chiral selenium-containing compounds by the formation of C–Se bonds is reviewed from three aspects. Review 1. Catalytic atroposelective synthesis of selenium-containing atropisomers by transition-metal-catalyzed C–H selenylation reactions Transition-metal-catalyzed enantioselective C–H activation

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

• obtaining medically interesting dactylicapnosine-like analogues for detailed study of their biological activity. Matoba et al. [45] reported the first enantioselective synthesis of the hasubanane alkaloid (−)-metaphanine (70) and the norhasubanane alkaloid (+)-stephadiamine (71) using a cyclohexane ring

• with 52% yield (Scheme 14). The authors [47] provided convincing evidence that the acyloin ring contraction is stereospecific, by replacing the benzil ᴅ-glucose in compound 76 at the C5 atom with an achiral prenyl group. In [49], Zhang and co-workers carried out the first enantioselective synthesis of

• . Next, ion 88 reacted with the isopropenyl group, forming intermediate 89, which was then converted into the desired 2,8-oxymethano-bridged diquinane 90 in 90% yield (Scheme 16). In the enantioselective synthesis of sesquiterpenoids (+)-cuparene (91) and (+)-tochuinyl acetate (92), Xie and co-workers

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

• yield substituted spiropyrrolidines (Scheme 1, path b) [9]. Additionally, an organocatalytic, enantioselective Michael addition/cyclization sequence of 3-aminooxindole Schiff bases with terminal vinyl ketones, catalyzed by a cinchona-derived base, has been reported to afford chiral spiroindolylpyrroles

• in high yields (Scheme 1, path c) [10]. Further expanding the scope of enantioselective approaches, a Michael/cyclization cascade reaction between 3-aminooxindoles and 2-enoylpyridines, catalyzed by a cinchonidine-based thiourea organocatalyst, was developed. Subsequent treatment with HCl in methanol

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• . provide a comprehensive review of machine learning applications in enantioselective organocatalysis, highlighting both achievements and remaining challenges [10]. Guo et al. present an automated flow chemistry system for nitration reactions, combining kinetic modeling with experimental optimization [11

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

• [20]. This compound significantly elevates reactive oxygen species levels in murine peritoneal macrophages (73 ± 12%) and exhibits potential as a lead for developing immunomodulatory agents. In 2021, Yang’s group reported a concise enantioselective total synthesis of (+)-cyclobutastellettolide B

• –Yang cyclization and the divergent starting point for accessing the other eight natural products (50–57). As an initial lead, two commercially available starting materials: (−)-citronellal (58) and diosgenin were employed (Scheme 7). (–)-Citronellal (58) was first converted to 59 via enantioselective

• inhibition (>5.75 × 10−4 M) against Alternaria solani [55]. In 2023, Suzuki's group pioneered the enantioselective total syntheses of preussomerins 97–99 through their photoredox strategy [49]. This study addressed the key challenge of controlling spiroacetal stereoselectivity through a 1,6-HAT process – a

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• chiral halogenated lactones, which could be useful in the enantioselective synthesis of valuable drug precursors. The syntheses feature the use of readily available and cheap starting materials, and we have also demonstrated some of these transformations on a gram scale. Halogen-containing butyrolactone

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

• Anna C. Renner Sagar S. Thorat Hariharaputhiran Subramanian Mukund P. Sibi Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota, 58105-5516, USA 10.3762/bjoc.21.174 Abstract This perspective is focused on enantioselective free radical reactions. It

• describes several important catalytic asymmetric strategies applied to enantioselective radical reactions, including chiral Lewis acid catalysis, organocatalysis, photoredox catalysis, chiral transition-metal catalysis and photoenzymatic catalysis. The application of electrochemistry to asymmetric radical

• transformations is also discussed. Keywords: chiral Lewis acid; electrochemistry; enantioselective radical reaction; organocatalysis; photoenzymatic catalysis; photoredox; Introduction Asymmetric catalysis plays an integral role in the enantioselective synthesis of organic compounds. A wide variety of

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• . Cycloisomerization of aromatic enynes governed by catalyst. Catalyst-dependent 1,2-migration in cyclization of 1-(indol-2-yl)-3-alkyn-1-ols. Gold-catalyzed cycloisomerization of N-propargyl-N-vinyl sulfonamides. Gold(I)-mediated enantioselective cycloisomerizations of ortho-(alkynyl)styrenes. Catalyst-controlled

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• , oxidant, and base-free conditions. An electrochemical enantioselective tandem C–H indolization of 2-alkynylanilines with 3-functionalized indoles towards 2,3′-biindolyl atropisomers was achieved by Zeng in 2025 (Scheme 7) [204]. After screening the reaction carefully, the optimal conditions were gained as

• . Indole skeletons were obtained successfully through electrochemical coupling of urea derivatives, dehydrogenative annulation of alkynes with anilines, annulation of o-arylalkynylanilines, cyclization of 2-ethynylanilines, selenocyclization of diselenides with 2-ethynylanilines, and enantioselective

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

• ligand led to excellent enantioselective induction during the hydrogenation step. Higher H2 pressure could promote the regeneration of Cu–H species [214]. Levulinic acid (LEV) Levulinic acid is a biodegradable C5 carboxylic acid with high potential as a platform chemical in the field of polymers, fuels

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

• The desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally

• synthesis of complex terpenoid and alkaloid natural products by strategically applying desymmetric enantioselective reduction. Advance before 2016 in this area has been overviewed in an elegant review article. Since then, a series of more challenging terpenoid and alkaloid natural products have been

• synthesized utilizing a desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds as a key transformation. This review will summarize the application of this strategy in the total synthesis of terpenoid and alkaloid natural products from the year 2016 to 2025. We first focus on the

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

• synthesis of natural products [10][55][56], in early 2009, our group disclosed a highly efficient four-step, enantioselective and diastereodivergent synthesis of (–)-chaetominine (1) and with one more step, of another diastereomer [57][58]. The strategy features a DMDO oxidation-triggered [59] double

• achieved the four-step enantioselective total synthesis of the proposed structure of aspera chaetominine A, and five-step enantioselective total synthesis of both the proposed and revised structures of aspera chaetominine B. The structure of aspera chaetominine B is revised to the known alkaloid

• alkaloids and antipodes. Enantioselective synthesis of the proposed structure of aspera chaetominine A. Enantioselective syntheses of both the proposed and revised structures of aspera chaetominine B. Supporting Information Supporting Information File 4: General methods and materials, experimental

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

• coupling of biaryls is designated as [30 20]. In addition to biaryls, axially chiral allenes are popular targets for asymmetric synthesis. Three examples of asymmetric reactions that form axially chiral allenes are shown in Scheme 4. For example, the enantioselective nucleophilic substitution to yield

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

• Technology, Guangzhou 510006, P. R. China 10.3762/bjoc.21.151 Abstract Enantioselective desymmetrization is employed as a powerful tool for the creation of chiral centers. Within this scope, the enantioselective desymmetrization of prochiral 1,3-diols, which generates chiral centers by enantioselective

• functionalization of one hydroxy group, offers beneficial procedures for accessing diverse structural motifs. In this review, we highlight a curated compilation of publications, focusing on the applications of enantioselective desymmetrization of prochiral 1,3-diols in the synthesis of natural products and

• asymmetric synthesis of them, driving the advancement of asymmetric methodologies [5][6][7][8][9]. Enantioselective desymmetrization of symmetric substrates has emerged as a pivotal methodology for the construction of chiral centers over the past few decades [10][11][12][13]. A series of reaction types have

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• ; inherent chirality; N-doped macrocycle; nonplanarity; regioselective cyclization; Introduction Chiral macrocycles have attracted significant research interest owing to their diverse applications in enantioselective recognition [1][2], catalysis [3][4], and circularly polarized luminescence [5][6

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

• asymmetric Mannich reactions, the past two decades have witnessed the remarkable evolution of CPA catalysis into one of the most versatile platforms for achieving diverse enantioselective transformations [3][4][5][6][7][8]. CPA catalysts are generally recognized as bifunctional catalysts with two distinct

• , including the asymmetric [2 + 2 + 2] cycloaddition of aryl-substituted polyynes and hydroarylation of alkynes [18][19]. In contrast, the application of asymmetric organocatalysis for enantioselective synthesis of chiral helicenes remains relatively underdeveloped compared to transition metal-catalyzed

• furan and pyridine moieties were successfully synthesized with high enantioselectivity. These compounds would be challenging to access using alternative asymmetric methods. In 2025, our group disclosed a highly efficient catalytic enantioselective double annulation approach for the asymmetric synthesis

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• ; single crystals; thiones; Introduction In the past several years, C–N atropisomers (C–N axially chiral compounds) owing to the rotational restriction around a C–N single bond have received great attention as new target molecules for catalytic asymmetric reactions. Highly enantioselective syntheses of

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

• enantioselective molecular recognition. Different chiral backbones were used for the construction of such chiral crown ethers, especially chiral 1,2-diols such as tartaric acid [5][6][7][8], propane-1,2-diol [9][10][11][12][13], cyclohexane-1,2-diol [14], carbohydrates [15], 1,1'-binapthyl-2,2'-diol (BINOL) [16

• was generated in both diastereomeric forms, namely (S,S)- and (R,S)-HiPr-M22. We believe that these systems are highly promising candidates for further application in enantioselective chemosensing or organocatalysis, e.g., after transformation into the corresponding BINOL phosphoric acids. However, at

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

• reaction type and the chirality type of resulting products. Perspective Isocyanide-based transformations Palladium-catalyzed isocyanide insertion reactions In 2018, Luo, Zhu, and co-workers developed a palladium-catalyzed enantioselective reaction between ferrocene-derived vinyl isocyanides 1 and aryl

• between β-ketoester 30 and di-tert-butyl azodicarboxylate (31), and the corresponding product 32 was obtained in 99% yield with 88% ee. A plausible reaction mechanism was proposed for this CPA-catalyzed enantioselective Groebke–Blackburn–Bienaymé reaction. As illustrated in Scheme 5b, the imine

• chiral INT-C, which, after imine-enamine tautomerization, led to the formation of final product 28. α-Acidic isocyanide-based transformations De novo arene formation In 2019, Zhu and co-workers developed the first example of catalytic enantioselective Yamamoto–de Meijere pyrrole synthesis [36][37