Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• shielding of the Si-side of the chiral iminium intermediate by bulky aryl groups leads to a stereoselective endo approach of the 1,3-dipole to the sterically less hindered Re-side of the intermediate iminium cation (Scheme 26). In this context, it is worth noting a work published in 2011, in which the

• and effective for the preparation of racemic cycloadducts [69][70][71]. Of interest are also non-catalytic reactions of 1,3-dipolar cycloaddition of azomethine ylides, which are formed in situ from the corresponding aldehydes and amino acid esters. In 2011, Shi and Gan proposed a stereoselective

• reacts with the nucleophile RXH to form the corresponding 3-substituted cyclopropenes. The latter reacts with azomethine ylide 67 to form cycloadducts in moderate yields. Density functional theory (DFT) calculations revealed that the regio- and endo-stereoselective formation of products in the observed

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• received, 1.45 g of 27 were obtainable during the second one from one batch (Scheme 3, step e) showing the scalability of this path. Moreover, besides 22 and 27, Konda and co-workers also accomplished the stereoselective syntheses of other diastereomers of the target tetrahydrofuran unit starting from 13

• reactions [76][77] for the assembly of fragment 45 (Scheme 6) [78]. Here, 40 and 42 served as the substrates for the allene-Prins reaction towards 43. Notably, the Bz-derivative of 40, 41, served as a starting point for a corresponding halichondrin B analog. The stereoselective course of this cyclization is

• , stereoselective dihydroxylation with AD-mix β and diol-protection yielded acetonide 57. Another DMP-oxidation, followed by HWE reaction, and deprotection of the diol motifs enabled the cyclization towards 60. After TBDMS-protection and reduction to the respective aldehyde (62), an alkylation with the α-sulfonyl

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• biaxial chirality, multistep sequential generation, and conversion from central to biaxial chirality, with the aim of providing new perspectives and methodologies for further development in this area. Keywords: axially chiral compounds; stereoselective synthesis; Introduction In recent years, axially

• , Hayashizaki, and Ito reported a highly stereoselective asymmetric cross-coupling reaction of 2-methylnaphthylmagnesium bromide with bromonaphthalene, catalyzed by a nickel complex with ferrocenylphosphine as the ligand, successfully synthesizing biaxially chiral molecules, namely 1,1':5',1"- and 1,1':4',1

• (Scheme 13) [29]. The reactions were carried out under mild conditions and required only low catalyst loading. The key to achieving high enantioselectivity lies in the stereoselective synthesis of the starting compounds which relies on polar–π interactions between an aryl component containing a highly

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• [22] and as insecticides [23]. Particularly, phosphate diesters are among the most important synthetic catalysts, such as the Akiyama–Terada catalyst that serves as a chiral Brønsted acid catalyst [24][25] and promotes a variety of stereoselective reactions. Phosphate diesters also catalyze the ring

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

• substitution pattern along the plane of symmetry, is known as planar chirality, as seen in metallocene and cyclophanes. Molecules containing planar chirality have greater relevance in materials science and stereoselective transformations [12][13]. The fourth branch of the chiral tree is helical chirality. A

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

• both homogeneous and heterogeneous systems, the hydrogenation of (hetero)arenes has become a cornerstone of modern synthesis for constructing saturated carbocycles and heterocycles [37]. When an appropriate ligand is paired with a transition-metal catalyst, stereoselective hydrogenation of aromatic

• catalyst in the presence of perchloric acid to obtain (−)-decahydrotabersonine, a product with a completely reduced aromatic ring (Scheme 13) [79]. Through the structural characterization of the product, the authors found that the hydrogenation was highly stereoselective, yielding only cis-hydrogenated

• products. This suggests that substrate induction during hydrogenation could effectively direct the process, enabling stereoselective product formation. Total synthesis of (±)-nominine by Natsume, 2004 Natural products with complex ring systems, such as bridged rings, spirocycles or highly rigid ring

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

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• aglycone sarmentogenin in 7 steps from 17-deoxycortisone. The synthesis features a scalable enzymatic C14–H α-hydroxylation, a Bestmann ylide-enabled one-step construction of the butenolide motif, a late stage Mukaiyama hydration, and a stereoselective C11 carbonyl reduction. Keywords: cardiac glycosides

• . Therefore, we decided to perform the Mukaiyama hydration on advanced intermediates. Next, a K-selectride-promoted chemo- and stereoselective reduction of the C3 carbonyl of 9 was realized to solely deliver 11 in 85% yield [33]. Then, 11 was subjected to Mukaiyama hydration conditions. Under the Fe(acac)3

• Bestmann ylide-enabled one-step construction of the butenolide motif, a late-stage Mukaiyama hydration, and a stereoselective C11 carbonyl reduction. We believe this chemoenzymatic synthetic strategy will inspire future endeavors towards the practical synthesis of complex steroids and other bioactive

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• ) [63]. Chauhan et al. developed a photocatalytic dual catalysis for an efficient stereoselective method that affords direct access to the pyrrolo[1,2-d][1,4]-oxazepin-3(2H)-ones 35 by merging organic eosin Y photoredox with carbene catalysis. Previous reports have shown eosin Y (Ered* in T1 [EY−•/EY

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

• , achieved the total synthesis of anhydroryanodol (10) and a formal synthesis of ryanodol (4) through a key low-valent titanium-mediated intramolecular stereoselective coupling of alkynes with 1,3-dicarbonyl compounds [52] (Scheme 9). To construct the oxygenated fused-ring system with contiguous

• . Treatment of 89 with Ti(OiPr)4/iPrMgCl promoted the intramolecular stereoselective alkyne–1,3-dicarbonyl coupling, resulting in the construction of the AB ring system. This transformation afforded tricyclic compound 91 as the major product, accompanied by minor amounts of by-product 90. Subjecting 91 to

• material. Key transformations included regioselective and stereoselective alkene epoxidation, organoselenium-mediated reductive cleavage of the α,β-epoxy ketone, and a hydroxy-directed stereospecific Mukaiyama hydration. These operations successfully introduced the C6 and C10 oxidation states, enabling the

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• formation of intermediate L is challenging because its ring-strain energy (Figure 1e, 52.1 kcal/mol) is higher than that of its counterpart, i.e. the bicyclo[3.2.0]heptane motif (28.3 kcal/mol) in H [24]. Herein, we report our recent results on the development of a novel strategy for the stereoselective

• construction of the tetracyclic core of Aspidosperma alkaloids. Our method involves an Ir-catalyzed PET reaction of K for the stereoselective formation of the cis-configured BC bicyclic core with an all-carbon quaternary center [25][26]. Computational studies suggest that the observed tandem PET reaction of K

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• ] and vaccines [15][16][17][18]. That is why new efficient and stereoselective methods for the synthesis of both Galf-containing mono- and oligosaccharide derivatives are highly demanded. It is a well-known fact that galactofuranose form constitutes only 5% in water solution of unprotected ᴅ-galactose

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

• 111 led to (±)-preterrenoid (107) with 68% yield, which was subjected to stereoselective oxidation with magnesium monoperoxyphthalate (MMPP) to give (±)-terrenoid (108) as a single diastereomer. Subsequent treatment of the key precursor 108 with catalytic amounts of NaOMe in MeOH resulted in

• -dihydronaphthalenes. Silva et al. have also developed an effective method for the stereoselective oxidation of tetralone derivatives using chiral hypervalent iodine reagents [61][62]. Hypervalent iodine compounds are widely used in organic synthesis as selective oxidants and enantiomerically pure reagents. In terms

• % yield. Jin et al. [85] reported an efficient photoinduced carboborative ring contraction of monounsaturated six-membered carbo- and heterocycles, allowing the regio- and stereoselective synthesis of functionalized cyclopentanes at gram scales. This method leads to the formation of compounds with

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• sugars (Figure 1) [42][43][44][45][46][47][48]. More specifically cycloaddition reactions of nitrones (1,3-dipoles) with N-aryl-substituted maleimides (electron-poor dipolarophiles) are a highly popular and versatile method for the formation of regio- and stereoselective pyrrolo-isoxazolidine-fused ring

• is fully consumed by the end of the five-minute reaction period. In academic and industrial communities alike, there is a high level of interest in catalytic methods of Green Chemistry that allow stereoselective transformations [125][126][127][128]. It is imperative to develop stereoselective

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

• can further undergo ring-opening or rearrangement reaction to assemble complex molecular frameworks. Additionally, quinone photoredox reactions involving single-electron transfer (SET) processes provide novel strategies for the stereoselective synthesis of useful structures such as spiroketals. This

• . This transformation proceeded via sequential regio- and stereoselective Norrish−Yang annulation, followed by intramolecular lactonization mediated by 12a. Notably, when the ethyl ester in 12 was replaced with a methyl group to form 14 with R = Et (Scheme 3), photoreaction of 14 led to 15 in 95% yield

• unprecedented 4,5-spirocyclic B/C ring system and a [4,3,1]propellane F/G/H ring fragment. In 2024, Yang's group achieved the construction of the ABCDE pentacyclic skeleton of phainanoids, leveraging Norrish–Yang cyclization to accomplish the regio- and stereoselective assembly of the rigid, sterically

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

• . Short procedures for their synthesis have been developed starting with levoglucosenone, which can be obtained in a single step from the pyrolysis of acid-treated cellulose. The processes use inexpensive reagents for the stereoselective C3 functionalization of the bicyclic ring system, with a subsequent

• influenza [7], while chlorinated analogues such as 3 have demonstrated activity against hepatitis C (Figure 1) [8]. Stereoselective methods to access halogenated γ-butyrolactones are therefore valuable, as they enable access to nucleoside analogues which have applications in treating cancer and certain

• epoxidations of 5 are highly stereoselective [44]. Unambiguous assignment of configuration for the diastereomers was not possible on the basis of the selective 1D NOE spectra due to the lack of informative crosspeaks. Limiting the amount of oxidant (H2O2 or peracetic acid) resulted in mixtures, suggesting that

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

• provides a way to avoid the use of stoichiometric chemical oxidants or reductants and to achieve new transformations that are highly regio- and stereoselective. Though not covered in this perspective, flow chemistry and mechanochemistry are also increasingly popular areas that hold significant potential

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

• -catalyzed cyclization approach using aromatic enyne derivatives, where substituent control governed the stereoselective syntheses of naphthalene and indene cores (Scheme 7) [14]. When the alkyne terminus of the substrate 27 bore an alkyl or aryl substituent, the Ph3PAuCl/AgOTf-catalyzed 6-endo-dig

• derivatives 31 (Scheme 7, path b). This work provided a novel approach for constructing substituted naphthalene and indene frameworks via gold-catalyzed cycloisomerization of 1,5-enynes. In 2016, Liu et al. achieved the stereoselective syntheses of furofuran and furopyran scaffolds from propargyl vinyl ethers

• )-catalyzed transformation to afford tetracyclic products 99 (Scheme 20, path c). This allenylation reaction provided efficient access to functionalized indole derivatives by regulating catalyst systems and substituent patterns. In 2010, the Iwasawa group established a stereoselective synthetic strategy

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• the MPO moiety by LC–MS and demonstrate its application to the stereochemical assignment of capsulactone (1) at the microgram scale. The strategy involves the optical resolution of MPO derivatives, chemical degradation of 1, and the stereoselective synthesis of four diastereomers. Results and

• that at C8–C9, and (3) methyl esterification (Scheme 2). The resulting C9–C12 fragment 7 was successfully detected at m/z 304.1 [M + Na]+ by LC–MS, as expected (see Figure 2b for the chromatogram). We then proceeded with the stereoselective synthesis of four diastereomers; 4-methoxy-3-methyl-4-oxobutan

• -2-yl 4-nitrobenzoates (2S,3S)-8, (2S,3R)-9, (2R,3R)-10, and (2R,3S)-11, as outlined in Scheme 3. The synthesis of (2S,3S)-8, and (2S,3R)-9 started from commercially available (3S)-12, and the stereogenic center at C2 was constructed via stereoselective methylation [27] to afford (2S,3S)-13. Due to

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

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

• stereoselective cyclopropanation accomplished the first total synthesis of (+)-isochamaecydin (26). On the other hand, starting from 122 and (−)-123, the authors adopted the same procedures as for the synthesis of 125 to obtain the pentacyclic product 126, which underwent the same functional group transformations

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

• stereoselective de novo approach [37]. The lactone was reduced with DIBAL-H to a semiketal, which was treated with the Lewis acid BF3·OEt2 to generate the putative oxa-carbenium 39. This cation triggered the Friedel–Crafts proposed cyclization with the electron-rich phenyl ring to give the dibenzocyclooctene

• -, chemo-, and stereoselective patterns in forming the polycycles could be trace back to same precursors or fragments, which would result in bioinspired total syntheses of natural products through controllable and selective chemical transformations. If there is only one single target molecule with an

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

• been employed to release carbon monoxide at relatively safer doses in biological systems using photoresponsive CO-releasing molecules (photo-CORMs) [4] because these have shown anti-inflammatory activity [5][6]. Photochemical denitrogenation of azoalkanes has been utilized in the stereoselective

• nucleophiles [7][8][9][10][11], radicals [12][13][14][15] and electrophiles [16][17][18] to give cyclobutanes and cyclobutenes [19][20], which are building blocks in regio- and stereoselective synthesis [21][22][23][24][25][26][27] (Scheme 1a). Additionally, BCB has been used in bioconjugation due to its high

• favorable. All MECI structures show partial stereochemical inversion. Following the initial σCN-bond cleavage, the carbon atom still bonded to N₂ begins to move towards inversion, indicating that dynamic effects help promote the stereoselective inversion. Conclusion We used multiconfigurational quantum

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

• of sets of atoms identified in step 2 (one or two sets). Before discussing applications to non-central chirality, we analyze two examples of stereoselective reactions that establish central chirality to illustrate the concept of stereogenic remoteness measured using the stereocontrol connectivity

• they do not share a common path. Typically, in stereoselective reactions involving central chirality, the proximity between the site of reaction and the points of stereo-differentiation means that the indices [ij] are expected to have small values. In general, j = 0 in the index [ij] of an addition

• generation of indices following the 3-step procedure using a prototypic program coded using Python or through coaching GPT-4.1. Stereoselective reactions were input as SMILES (for Python) or InChI (for GPT-4.1) of the starting materials and products, and the corresponding indices were generated automatically

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

• available has prevented its practical use, and synthesis methods for tricyclic-PGDM methyl ester are required. Based on the utilization of oxidative radical cyclization for the stereoselective construction of the cyclopentanol subunit with three consecutive stereocenters, we describe an asymmetric total

• the total syntheses of PGs via organocatalysis, and enyne cycloisomerization, respectively. Thus, from a strategic viewpoint, developing alternative synthetic approaches for the stereoselective construction of the highly substituted cyclopentanol core framework in compound 4 may advance the efficient

• an inseparable mixture of diastereomers at C-15 in a ratio of 1.0/1.1 (1H NMR analysis). Having established a route to the bicyclic hemiketal 21, we investigated the stereoselective introduction of an allyl moiety at C8 for the synthesis of compound 25 according to the strategy in Scheme 3. Treatment