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Search for "diastereoselective" in Full Text gives 332 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile
- Melina Goga,
- Hao Zong,
- James Franco,
- Jazmine Prana,
- Rudolph Michel,
- Antonia Muro,
- Elana Rubin,
- Janet Brenya,
- Henk Eshuis and
- Magnus W. P. Bebbington
Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56
- dienone substrates for this study. Conclusion Methodical investigation of substrate scope allied with detailed computational modelling have improved the understanding of diastereoselective sulfone formation from the reaction of Rongalite and readily available dienones. We have also established that
Graphical Abstract
Figure 1: Rongalite as an equivalent of the unstable hyposulfite ion.
Scheme 1: Progression of Rongalite conjugate additions.
Figure 2: Sulfone diastereomers 1a and 1b.
Scheme 2: Verification of relative stereochemistry by i) sulfide oxidation and ii) derivatization.
Scheme 3: Reactions of sterically hindered substrates.
Figure 3: Minimized structure of dienone 7 (calculated using the PBE0 functional [26] and the def2-SVP basis set [27]...
Figure 4: Modeling of cyclization transition states (the solvating acetic acid molecules were omitted for cla...
Figure 5: Unsuccessful substrates.
Scheme 4: Initial reactivity comparison with p-toluenesulfinate.
Scheme 5: Preparation of anticipated products in competition experiments with Rongalite and other sulfinates.
Scheme 6: Exchange experiment.
Scheme 7: Double intermolecular additions.
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
- iminoester 1 with tert-butyl acrylic acid ester 4 occurs first. This is followed by condensation of pyrrolidine 9 with cinnamic aldehyde (10) to form azomethine ylide B, which enters into a second diastereoselective 1,3-DC with various electrophilic alkenes. The authors used acrylic acid esters, vinylphenyl
- reaction of analogous azomethine ylides with 2-arylacrylates was catalyzed by chiral binol-based phosphoric acids [65]. In 2023, Retamosa and Sansano carried out a diastereoselective synthesis of polysubstituted pyrrolidines 59 under mild conditions via 1,3-dipolar cycloaddition between tert
- yields of up to 94% (Scheme 53). In 2019, the Kanizsai group described the regio- and diastereoselective 1,3-dipolar cycloaddition of 2H-azirines to azomethine ylides generated in situ from isatins and α-amino acids, resulting in a previously unknown aziridine-fused spiro[imidazolidine-4,3′-oxyindole
Graphical Abstract
Scheme 1: Strategies for the preparation of pyrrolidine derivatives by (3 + 2) cycloaddition of azomethine yl...
Scheme 2: (3 + 2) Cycloaddition of iminoesters to dimethylmaleate.
Scheme 3: Cycloaddition of 1 with various dipolarophiles catalyzed by Ag(I)-L1.
Scheme 4: Cycloaddition of 1 with tert-butyl acrylate catalyzed by Ag(I)-L2.
Scheme 5: Cycloaddition of 1 with dimethyl maleate catalyzed by Cu(I)-L3.
Scheme 6: Cycloaddition of 1 with alkenes catalyzed by Zn(II)-t-Bu-BOX (L4).
Scheme 7: (3 + 2) Cycloaddition of iminoesters to acrylates.
Scheme 8: Catalytic double (3 + 2) cycloaddition to form pyrrolizidine derivatives.
Scheme 9: (3 + 2) Cycloaddition of iminoethers to vinyl phenyl sulfone.
Scheme 10: Regiodivergent and enantioselective synthesis of pyrrolidines 16 and 17.
Scheme 11: Substrate-controlled regioreversible "normal" and "incomplete" 1,3-dipolar cycloaddition.
Scheme 12: Enantioselective synthesis of exo-/endo-pyrrolidines.
Scheme 13: (3 + 2) Cycloaddition of iminoethers 21 to dipolarophiles 22–24.
Scheme 14: Synthesis of bicyclic pyrrolidines 29 from cyclopentene-1,3-diones.
Scheme 15: (3 + 2) Cycloaddition of aldimine esters and allyl alcohols using copper-ruthenium catalysis.
Scheme 16: Synthesis of 3,3-difluoro- and 3,3,4-trifluoropyrrolidine derivatives.
Scheme 17: Use of iminoesters from natural compounds and pharmaceuticals for reactions with 1,1-difluoro- and ...
Scheme 18: Reaction of iminoesters with 1,3-enynes.
Scheme 19: Synthesis of pyrrolidines from iminoesters and vinyl(hetero)arenes.
Scheme 20: Synthesis of exo-pyrrolidines 42 and 43.
Scheme 21: Enantioselective synthesis of heteroarylpyrrolidines 45 and 46.
Scheme 22: Catalytic reaction of (3 + 2) cycloaddition of imines 12 to benzofulvenes 47.
Scheme 23: Fullerene as a dipolarophile in (3 + 2) cycloaddition reactions.
Scheme 24: Asymmetric synthesis of optically active tetrasubstituted pyrrolidines 54.
Scheme 25: (3 + 2) Cycloaddition reaction of imines 55 and α,β-unsaturated aldehydes.
Scheme 26: Probable mechanism of enantioselective (3 + 2) cycloaddition of azomethine ylides to α,β-unsaturate...
Scheme 27: Cycloaddition between iminoesters 12 and sulfinylimines 58.
Scheme 28: (3 + 2) Cycloaddition between triarylideneacetylacetone and azomethine ylides in the presence of ti...
Scheme 29: Stereoselective synthesis of decahydropyrrolo[2,1,5-cd]indolizine 66.
Scheme 30: Synthesis of policyclic derivatives 71 and 72.
Scheme 31: Catalytic аsymmetric (3 + 2) сycloaddition of 2-pyridylimines with N-methylmaleimide.
Scheme 32: Catalytic аsymmetric (3 + 2) сycloaddition of 2-pyridylimines 1 with other dipolarophiles.
Scheme 33: Enantioselective (3 + 2) cycloaddition of silylimine with various dipolarophiles.
Scheme 34: Proposed mechanism of formation of pyrrolidines 78.
Scheme 35: Synthesis of polyheterocyclic pyrrolidines 82–91.
Scheme 36: Synthesis of spirocyclic (95) and fused (96) pyrrolidines.
Scheme 37: (3 + 2) Cycloaddition involving aromatic aldehydes 97, N-propargylmaleimide (98) and α-amino acids ...
Scheme 38: Synthesis of pyrrolizidines 106 and by-product 107.
Scheme 39: Iridium-catalyzed three-component cascade (3 + 2) cycloaddition.
Scheme 40: Intramolecular (3 + 2) cycloaddition of N-alkenylpyrrole-2-carbaldehyde 110 and α-amino acids.
Scheme 41: Three-component (3 + 2) cycloaddition involving fullerene.
Scheme 42: Four-component stereoselective one-pot synthesis of spiro-cycloadducts 119–122.
Scheme 43: Reactions of azomethine ylide 123 with cyclopropenes.
Scheme 44: Three-component reactions involving ninhydrin, cyclopropenes and acyclic α-amino acids.
Scheme 45: Reaction of cyclopropenes 138 with the N-protonated form of Ruhemann purple 137.
Scheme 46: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and amin...
Scheme 47: (3 + 2) Cycloaddition of cyclohexenone 143, isatins 140 and aminomalonic diesters 141, catalyzed by...
Scheme 48: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and amin...
Scheme 49: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and benz...
Scheme 50: (3 + 2) Cycloaddition involving isatins, azetidine-2-carboxylic acid, maleimides or itaconimides.
Scheme 51: (3 + 2) Cycloaddition involving isatins, amino acids and tetraethylvinylidenebis(phosphonate).
Scheme 52: Synthesis of spirooxindoles 156 from triarylideneacetylacetones 155.
Scheme 53: Synthesis of spirooxindole derivatives 157–160.
Scheme 54: Synthesis of hybrid spiro-heterocycles 164–166.
Scheme 55: Formation of azomethine ylide from isatin and sarcosine.
Scheme 56: (3 + 2) Cycloaddition involving isatins, amino acids and trans-3-benzoylacrylic acid.
Scheme 57: Regioselective synthesis of spirooxindoles 170.
Scheme 58: Synthesis of hybrid spiro-heterocycles 86.
Scheme 59: (3 + 2) Cycloaddition involving acenaphthenequinones, amino acids and cyclopropenes.
Scheme 60: Synthesis of hybrid glyco-3-nitrochromane cycloadducts 179.
Scheme 61: Synthesis of spiro[indenoquinoxaline-(thia)pyrrolizidines] 90a.
Scheme 62: Three-component reactions of cyclopropenes, 11H-indeno[1,2-b]quinoxalin-11-onesand α-amino acids, s...
Scheme 63: Synthesis of hybrid glyco-3-nitrochromane cycloadducts 92.
Scheme 64: (3 + 2) Cycloaddition of 11H-benzo[4,5]imidazo[1,2-a]indol-11-one (189) with cyclopropenes and male...
Scheme 65: Diastereoselective synthesis of spiro derivatives of barbituric acid from alloxan 193, α-amino acid...
Scheme 66: Probable mechanism of formation of azomethine ylide from alloxan and ʟ-proline.
Scheme 67: Three-component reactions involving tryptanthrin 196, α-amino acids and cyclopropenes.
Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization
- Haruna Imazu,
- Hitoshi Izu,
- Yasuhiro Ohki and
- Masamichi Ogasawara
Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42
- or Mo/(R)-L3 discriminate the two enantiomers in rac-1 efficiently to provide a mixture of the corresponding AMD product (S,S)-2 and unreacted antipodal substrate (R)-1 with the krel values of up to 1.5 × 103. The AMD/KR reactions of rac-1 were highly diastereoselective: under the optimized
Graphical Abstract
Scheme 1: Asymmetric metathesis dimerization/kinetic resolution of racemic planar-chiral vinylferrocene/vinyl...
Scheme 2: Preparation of racemic planar-chiral vinylcymantrene substrates rac-1a–c.
Figure 1: ORTEP drawing of the X-ray structure of (S,S)-(–)-2b with atom numbering (thermal ellipsoids set at...
Figure 2: Structures of less-reactive enantiomers in three representative planar-chiral vinylmetallocene subs...
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
- with four consecutive chiral axes [41]. Rhodium-catalyzed enantio- and diastereoselective cycloaddition of 1,2-bis(arylpropiolyl)benzenes with monoalkynes. Synthesis of remote double axially chiral phosphoric acids. Construction of chiral biaxial diphosphine ligand. Atroposelective synthesis of
Graphical Abstract
Figure 1: Natural products with various stereogenic axes.
Scheme 1: Iridium complex-catalyzed asymmetrical synthesis of axially chiral (a) teraryl compounds 3 [40] and (b)...
Scheme 2: Rhodium-catalyzed enantio- and diastereoselective cycloaddition of 1,2-bis(arylpropiolyl)benzenes w...
Scheme 3: Synthesis of remote double axially chiral phosphoric acids.
Scheme 4: Construction of chiral biaxial diphosphine ligand.
Scheme 5: Atroposelective synthesis of biaxially chiral 1,4-distyryl-2,3-naphthalene diols.
Scheme 6: H-Bond-enabled enantioselective synthesis of remote biaxially chiral amides mediated by the counter...
Scheme 7: Enantioselective synthesis of biaryl products with twofold chiral axes.
Scheme 8: Iridium-catalyzed C–H alkylation to obtain the distal biaxial atropisomers.
Scheme 9: Co/SPDO-catalyzed biaxial bridged terphenyl compounds.
Scheme 10: Atroposelective Co-catalyzed synthesis of pyridoindolones with two distinct C–N axes.
Scheme 11: NHC organocatalytic synthesis of fused 1,4-biaxial uracils with C–C and C–N chiral axes.
Scheme 12: Synthesis of the first biaxially chiral compound reported by Ito and co-workers [35].
Scheme 13: Synthesis of chiral homoaryl compounds by Suzuki–Miyaura coupling.
Scheme 14: Structurally complex APIs with multiple chiral axes.
Scheme 15: Synthesis of helicenes containing stereogenic axes.
Scheme 16: Chiral NHC–Pd complex-catalyzed Suzuki–Miyaura cross-coupling reaction for the synthesis of block-t...
Scheme 17: Highly enantioselective C–H arylation of heteroarenes.
Scheme 18: Synthesis of novel axially chiral N-arylcarbazole skeletons by the assembly of azidonaphthalenes an...
Scheme 19: Catalytic enantioselective synthesis of axially chiral polycyclic aromatic hydrocarbons.
Scheme 20: Catalytic synthesis of biaxial triphenylene block-transfer isomers.
Scheme 21: A Pd(II)-catalyzed trans-selective C–H alkenylation strategy through thioether-directed olefination....
Scheme 22: Synthesis of N-arylphthalimides from prochiral maleimides and NHC-activated dienolides.
Scheme 23: Ni-catalyzed synthesis of triaxially chiral polysubstituted naphthalene scaffolds.
Scheme 24: Enantioselective Ni-catalyzed Suzuki–Miyaura cross-coupling reaction.
Scheme 25: The stereoselective synthesis of axial chiral indole–quinoline systems.
Scheme 26: The synthesis of bisbenzofuran atropisomeric oligoarenes containing two distal C–C stereogenic axes....
Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation
- Arthur A. Puzyrkov,
- Andrew S. Drachuk,
- Ekaterina A. Popova,
- Alexander V. Stepakov and
- Vitali M. Boitsov
Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20
- synthesis of spirobarbiturates via a [3 + 2] cycloaddition reaction of azomethine ylides, we present for the first time a three-component diastereoselective synthesis of hybrid systems containing spiro-fused cyclic fragments of barbituric acid and pyrrolo[3,4-a]pyrrolizidine. It was found that azomethine
Graphical Abstract
Scheme 1: Biologically active compounds with a spirobarbiturate moiety in their structure [7-12].
Scheme 2: Biologically active alkaloids with a pyrrolizidine moiety.
Scheme 3: Previous studies on the three-component synthesis of spirobarbiturates.
Scheme 4: Synthesis of racemic spirobarbiturates 4a–p via one-pot three-component reaction of alloxan (1), ʟ-...
Scheme 5: A plausible mechanism of spirobarbiturate formation from alloxan (1), ʟ-proline (2), and N-substitu...
Figure 1: Schematic structures of endo- and exo-adducts of spirobarbiturates 4.
Figure 2: X-ray crystal structures of compounds 4b (CCDC 2391172, left) and 4c (CCDC 2391171, right).
Figure 3: Unit cell packing of products 4b (left) and 4c (right).
Figure 4: HS mapped with dnorm for compounds 4b (left) and 4c (right).
Figure 5: A segment of the crystal structure of compound 4b with the HS (dnorm), showing intermolecular conta...
Figure 6: A segment of the crystal structure of compound 4c with the HS (dnorm), showing intermolecular conta...
Figure 7: Microscopic images of treated cells and state of the actin cytoskeleton of Sk-mel-2 cells after cul...
Figure 8: Docked view of compounds 4f, 4g, 4i, 4k, and 4l with the target protein (PDB ID: 8DNH).
Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure
- Ilia A. Pilipenko,
- Mikhail V. Grigoriev,
- Olga Yu. Ozerova,
- Igor A. Litvinov,
- Darya V. Spiridonova,
- Aleksander V. Vasilyev and
- Sergey V. Makarenko
Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5
- summary, we proposed a diastereoselective method for the synthesis of vicinal trichloromethylnitrocyclopropanes by forming a cyclopropane ring from a trichloromethylnitroethene substrate and an active methylene component. Variation of the methylene component structure – linear (malononitrile, methyl
Graphical Abstract
Figure 1: Two natural trichloromethyl-containing compounds.
Scheme 1: Approaches to the synthesis of vic-trifluoromethylnitrocyclopropanes.
Scheme 2: Synthesis of monocyclic trichloromethylnitrocyclopropanes 2–5.
Scheme 3: Synthesis of spiro-fused trichloromethylnitrocyclopropane 6.
Scheme 4: Synthesis of spiro-fused trichloromethylnitrocyclopropanes 7–9. i: 1.5 AcOK, MeOH, rt, 3 h.
Scheme 5: Main NOE correlations in 9a, 9b.
Scheme 6: Proposed mechanism of the formation of trichloromethylnitrocyclopropanes.
Figure 2: Geometry of 2 in the crystal.
Figure 3: Geometry of 3 in the crystal.
Figure 4: Geometry of 9a in the crystal.
Figure 5: Geometry of 9b in the crystal.
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
- difficult for the substrate to coordinate with the metal catalyst. In 2021, Glorius and co-workers reported an enantio- and diastereoselective complete hydrogenation of substituted benzofurans 65 in a one-pot cascade reaction (Scheme 8) [62]. This method facilitates the controlled installation of up to six
- diastereoselective hydrogenation of symmetrical 2,5-DKP (2,5-dipiperazinone) 67 using a rhodium complex (Scheme 8) [63]. The saturated pentacyclic compound 68 was obtained in high yield and excellent diastereoselectivity. The hydrogen atoms in the final product were all arranged in cis configuration. Key features of
- -tetrahydroisoquinoline natural products, (±)-lemonomycinone and (±)-renieramycin, featuring as key steps a dearomative nucleophilic addition and diastereoselective hydrogenation of a dihydroisoquinoline (Scheme 16) [85]. Starting from pentasubstituted isoquinoline 117, the authors utilized a dearomative nucleophilic
Graphical Abstract
Scheme 1: The association between dearomatization and natural product synthesis.
Scheme 2: Key challenges in hydrogenation of aromatic rings.
Scheme 3: Hydrogenation of heterocyclic aromatic rings.
Scheme 4: Hydrogenation of the carbocyclic aromatic rings.
Scheme 5: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 6: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 7: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 8: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 9: Total synthesis of (±)-keramaphidin B by Baldwin and co-workers.
Scheme 10: Total synthesis of (±)-LSD by Vollhardt and co-workers.
Scheme 11: Total synthesis of (±)-dihydrolysergic acid by Boger and co-workers.
Scheme 12: Total synthesis of (±)-lysergic acid by Smith and co-workers.
Scheme 13: Hydrogenation of (−)-tabersonine to (−)-decahydrotabersonine by Catherine Dacquet and co-workers.
Scheme 14: Total synthesis of (±)-nominine by Natsume and co-workers.
Scheme 15: Total synthesis of (+)-nominine by Gin and co-workers.
Scheme 16: Total synthesis of (±)-lemonomycinone and (±)-renieramycin by Magnus.
Scheme 17: Total synthesis of GB13 by Sarpong and co-workers.
Scheme 18: Total synthesis of GB13 by Shenvi and co-workers.
Scheme 19: Total synthesis of (±)-corynoxine and (±)-corynoxine B by Xia and co-workers.
Scheme 20: Total synthesis of (+)-serratezomine E and the putative structure of huperzine N by Bonjoch and co-...
Scheme 21: Total synthesis of (±)-serralongamine A and the revised structure of huperzine N and N-epi-huperzin...
Scheme 22: Early attempts to indenopiperidine core.
Scheme 23: Homogeneous hydrogenation and completion of the synthesis.
Scheme 24: Total synthesis of jorunnamycin A and jorumycin by Stoltz and co-workers.
Scheme 25: Early attempt towards (−)-finerenone by Aggarwal and co-workers.
Scheme 26: Enantioselective synthesis towards (−)-finerenone.
Scheme 27: Total synthesis of (+)-N-methylaspidospermidine by Smith, Grigolo and co-workers.
Scheme 28: Dearomatization approach towards matrine-type alkaloids.
Scheme 29: Asymmetric total synthesis to (−)-senepodine F via an asymmetric hydrogenation of pyridine.
Scheme 30: Selective hydrogenation of indole derivatives and application.
Scheme 31: Synthetic approaches to the oxindole alkaloids by Qi and co-workers.
Scheme 32: Total synthesis of annotinolide B by Smith and co-workers.
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
- , hydroboration/oxidation, and an oxidative cyclization protocol. The diastereomers were separable by column chromatography, leading to this faster and more scalable procedure to be performed preferentially over a six-step diastereoselective sequence. After silyl ether deprotection, the Wagner–Meerwein-type
Graphical Abstract
Scheme 1: Representatives of steroid alkaloid classes. Marked in blue is the steroidal cholestane framework, ...
Scheme 2: Subclasses of Veratrum alkaloids: jervanine, veratramine and cevanine-type [8].
Scheme 3: Flow chart presentation of the synthesis of (−)-englerin A developed by the Christmann group [10].
Scheme 4: Structures and year of synthesis of the three types of Veratrum alkaloids reported in the literatur...
Scheme 5: Key step in the synthesis of cyclopamine (6) by the Giannis group [21].
Scheme 6: Overview of the semisynthesis of cyclopamine (6) reported by the Giannis group in 2009 [21].
Scheme 7: Key steps in the synthesis of cyclopamine (6) by the Baran group [23].
Scheme 8: Overview of the total synthesis of cyclopamine (6) by the Baran group in 2023 [23].
Scheme 9: Key steps in the synthesis of cyclopamine (6) by the Zhu/Gao group [25].
Scheme 10: Overview of the total synthesis of cyclopamine (6) by the group of Zhao/Gao in 2023 [25].
Scheme 11: Key steps in the synthesis of cyclopamine (6) by the Liu/Qin group [26].
Scheme 12: Overview of the semisynthesis of cyclopamine (6) by the Liu/Qin group in 2024 [26].
Scheme 13: Key steps in the synthesis of jervine (12) by the Masamune group [14].
Scheme 14: Overview of the total synthesis of jervine (12) by the Masamune group in 1968 [14].
Scheme 15: Color-coded schemes of the presented cyclopamine (6) syntheses by Giannis, Baran, Zhu/Gao, and Liu/...
Scheme 16: Key steps in the total synthesis of veratramine (13) by the Johnson group [15].
Scheme 17: Overview of the total synthesis of veratramine (13) by the Johnson group in 1967 [15].
Scheme 18: Key steps in the synthesis of veratramine (13) by the Zhu/Gao group [25].
Scheme 19: Shortened overview of the total synthesis of veratramine (13) by the Zhu/Gao group in 2023 [25].
Scheme 20: Key steps in the synthesis of veratramine by the Liu/Qin group [26].
Scheme 21: Overview of the semisynthesis of veratramine (13) by the Liu/Qin group in 2024 [26].
Scheme 22: Key steps in the synthesis of veratramine (13) by the Trauner group [27].
Scheme 23: Overview of the total synthesis of veratramine (13) by the Trauner group in 2025 [27].
Scheme 24: Key steps in the synthesis of verarine (14) by the Kutney group [16-19].
Scheme 25: Overview of the total synthesis of verarine (14) by the Kutney group reported 1962–1968 [16-19].
Scheme 26: Color-coded schemes of the presented veratramine-type alkaloid synthesis of Zhu/Gao, Liu/Qin and Tr...
Scheme 27: Structures of veracevine (86), veratridine (87), and cevadine (88).
Scheme 28: Key step in the semisynthesis of verticine (15) by the Kutney group (1977) [20,46].
Scheme 29: Overview of the semisynthesis of verticine (15) by the Kutney group (1977) [20,46].
Scheme 30: Key step of the total synthesis of (±)-4-methylenegermine (17) by the Stork group (2017) [22].
Scheme 31: Overview of the total synthesis of (±)-4-methylenegermine (17) by the Stork group (2017) [22].
Scheme 32: Key step of the total synthesis of heilonine (16) by Cassaidy and Rawal (2021) [24].
Scheme 33: Overview of the total synthesis of heilonine (16) by Cassaidy and Rawal (2021) [24]. FGI: functional gr...
Scheme 34: Key steps of the synthesis of heilonine (16) by Dai and co-workers (2024) [28].
Scheme 35: Overview of the total synthesis of heilonine (16) by Dai and co-workers (2024) [28].
Scheme 36: Key steps of the total synthesis of zygadenine (18) reported by Luo and co-workers [29].
Scheme 37: Overview of the total synthesis of zygadenine (18) by Luo and co-workers (2023) [29].
Scheme 38: Key step of the divergent total syntheses of highly oxidized cevanine-type alkaloids by Luo and co-...
Scheme 39: Divergent syntheses of highly oxidized cevanine-type alkaloids by Luo and co-workers (2024) [30].
Scheme 40: Color-coded overview of the presented cevanine-type alkaloid syntheses [10,20,22,24,28-30,46]. LLS: longest linear sequen...
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
- , and introduction of an isopropenyl group afforded compound 75. Subsequent protection of the vicinal diol as a boronic ester and diastereoselective reduction of the C3 carbonyl group yielded compound 76. Esterification with acylating reagent 77 under basic conditions, followed by boronic ester removal
- diastereoselective reduction of the C3 ketone, the acyl pyrrole group was introduced to yield 81. During acyl pyrrole installation, excess KHMDS enolized the lactone to suppress lactone-C3 hydroxy transesterification. However, α-chlorination of the ester carbonyl was unavoidable. Finally, reductive dechlorination
- , thus establishing the core C and D rings. Base-mediated equilibration fully converted 93 into lactone 94. Finally, selective hydroxy protection in 94, diastereoselective introduction of the C10 secondary alcohol, and global deprotection completed the total synthesis of anhydroryanodol (10). Application
Graphical Abstract
Scheme 1: Representative Ryania diterpenoids and their derivatives.
Scheme 2: Deslongchamps’s total synthesis of ryanodol (4).
Scheme 3: Deslongchamps’s total synthesis of 3-epi-ryanodol (5).
Scheme 4: Inoue’s total synthesis of ryanodol (4).
Scheme 5: Inoue’s total synthesis of ryanodine (1) from ryanodol (4).
Scheme 6: Inoue’s total synthesis of cinncassiol A (9), cinncassiol B (7), cinnzeylanol (6), and 3-epi-ryanod...
Scheme 7: Reisman’s total synthesis of (+)-ryanodol (4).
Scheme 8: Reisman’s total synthesis of (+)-ryanodine (1) and (+)-20-deoxyspiganthine (2).
Scheme 9: Micalizio’s formal total synthesis of ryanodol (4).
Scheme 10: Zhao’s total synthesis of garajonone (8).
Scheme 11: Zhao’s formal total synthesis of ryanodol (4) and ryanodine (1).
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
- rearrangement to produce lactone 58 with a yield of 78%. The last stage of the synthesis proceeds through a chemo- and diastereoselective reduction of lactone 58, containing the desired trans-fused bicyclo[3.3.0]octane ring system, leading to the target 4β-acetoxyprobotryane-9β,15α-diol (52). An alternative
Graphical Abstract
Scheme 1: Ozonolysis–cyclization sequence in the synthesis of echinopine A (3).
Scheme 2: Ozonolysis–cyclization sequence in the synthesis of taiwaniaquinoids 7–12.
Figure 1: Iridoid skeleton.
Scheme 3: Ozonolysis–cyclization sequence in the synthesis of compounds 17a,b, 18 and 19 with iridoid topolog...
Scheme 4: Oxidation–aldol condensation sequence in the synthesis of compounds 21 and 23 with iridoid topology....
Scheme 5: Oxidation–aldol condensation sequence in the synthesis of compounds 29 and 30 with iridoid topology....
Scheme 6: Method for ring contraction in the absence of a double bond in a six-membered ring of triterpenoids....
Scheme 7: Oxidation–Dieckmann cyclization sequence in the synthesis of a new nortriterpenoid 39.
Scheme 8: Oxidation–Dieckmann cyclization sequence in the synthesis of 18,19-di-nor-cholesterol (40).
Scheme 9: Oxidation–cyclization sequence in the synthesis of 3-ethyl-substituted betulinic acid derivatives 49...
Scheme 10: Benzilic acid-type rearrangement in the synthesis of 4β-acetoxyprobotryane-9β,15α-diol (52).
Scheme 11: Benzilic acid-type rearrangement in the synthesis of (−)-taiwaniaquinone H (11).
Scheme 12: Benzilic acid-type rearrangement in the synthesis of dactylicapnosines A (63) and B (64).
Scheme 13: Aza-benzilic acid-type rearrangement in the synthesis of (+)-stephadiamine (71).
Scheme 14: α-Ketol rearrangement in the synthesis of saffloneoside (73).
Scheme 15: Conversion of (−)-preaustinoid A (80) to (−)-preaustinoid B (81) via α-ketol rearrangement.
Scheme 16: α-Ketol rearrangement in the synthesis of 2,8-oxymethano-bridged diquinane 90.
Scheme 17: Oxidative ring contraction during the synthesis of (+)-cuparene (91) and (+)-tochuinylacetate (92).
Scheme 18: Semipinacol rearrangement in the synthesis of diterpenoids 97–100.
Scheme 19: Co-catalyzed homoallyl-type rearrangement in the syntheses of meroterpenes 106–109.
Scheme 20: Ring contraction reaction promoted by TTN·3H2O and HTIB in the synthesis of indanes.
Scheme 21: Rearrangement involving a hypervalent iodine compound in the synthesis of derivative 120.
Scheme 22: Wolff rearrangement in the synthesis of taiwaniaquinones A (7), F (8), taiwaniaquinols B (10), D (1...
Scheme 23: Wolff rearrangement in the synthesis of cheloviolene C (128), seconorrisolide B (129), and seconorr...
Scheme 24: Wolff rearrangement in the synthesis of (−)-pavidolide B (134).
Scheme 25: Wolff rearrangement in the synthesis of presilphiperfolan-8-ol (141).
Scheme 26: Photochemical rearrangement in the synthesis of cyclopentane derivatives 147a,b.
Scheme 27: Synthesis of cyclopentane derivatives 147a and 151.
Scheme 28: Photochemical rearrangement in the synthesis of cyclopentane derivative 153.
Scheme 29: Photochemical rearrangement in the synthesis of tricyclic ketones 155, 156.
Scheme 30: Photochemical rearrangement in the synthesis of cis/trans salts 160.
Figure 2: Scope of the photoinduced carboborative ring contraction of steroids. Reaction conditions: steroid ...
Scheme 31: Photoinduced carboborative ring contraction in the synthesis of artalbic acid (180).
Scheme 32: Synthetic versatility of the photoinduced carboborative ring contraction.
Scheme 33: Methods of disclosure of epoxide 189.
Scheme 34: Methods of disclosure of epoxide 190.
Scheme 35: Rearrangement of α,β-epoxy ketone 197.
Scheme 36: Acid-induced rearrangement in the synthesis of perhydrindane ketones 202 and 205.
Scheme 37: Rearrangement of epoxyketone 208 in the synthesis of huperzine Q (206).
Scheme 38: Rearrangement of epoxide 212 under the action of Grignard reagent.
Scheme 39: Semipinacol rearrangement of epoxide 220 in the synthesis of (−)-citrinadin A (217) and (+)-citrina...
Scheme 40: Semipinacol rearrangement of epoxide 225 in the synthesis of hamigeran G (223).
Scheme 41: Semipinacol rearrangement of epoxide 231 in the synthesis of (−)-spirochensilide A (228).
Scheme 42: Wagner–Meerwein rearrangement in the synthesis of compound 234 with iridoid topology.
Scheme 43: Wagner–Meerwein rearrangement in the synthesis of compound 238 with iridoid topology.
Scheme 44: Wagner–Meerwein rearrangement in the synthesis of compound 241 with iridoid topology.
Scheme 45: Wagner–Meerwein rearrangement in the synthesis of lupane derivatives 245, 246, 248, and 249.
Scheme 46: Wagner–Meerwein rearrangement in the synthesis of weisaconitine D (252) and cardiopetaline (255).
Scheme 47: Wagner–Meerwein rearrangement in the synthesis of cardiopetaline (255).
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
- , a highly diastereoselective method for the synthesis of dihydrospiro[indoline-3,2'-pyrrole]-2-ones has been developed (Scheme 1, path a) [7]. This transformation proceeds via a Lewis acid-mediated conjugate addition of vinyl azides to electron-deficient alkenes, followed by denitrogenative
Graphical Abstract
Figure 1: Natural and synthetic bioactive spiro[indoline-3,2'-pyrrolidine] derivatives.
Scheme 1: Previous approaches and our work.
Scheme 2: The reaction of 2-arylindoles 1 with α,β-unsaturated ketones 2. aIsolated yield of the 5 mmol scale...
Scheme 3: The scope of the Fe-catalyzed spirocyclization. aIsolated yield of the 4.2 mmol scale experiment.
Scheme 4: The proposed mechanism of product 4 formation.
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
- by the Yang group [22]. Installation of the hydroxymethyl group in 4 was achieved through sequential formylation and reduction. Compound 4 then underwent a one-pot, substrate-controlled diastereoselective Johnson−Claisen rearrangement/acetylation to install ester 5. Treating 5 with m-CPBA (meta
- , followed by diastereoselective α-alkylation, produced 38. A Wittig reaction and subsequent deketalization converted the ketone in 38 to the terminal alkene 39, allowing for subsequent sequential chemoselective hydrogenations: first, hydrogenation of the exo-olefin using Wilkinson’s catalyst proceeded with
- -obscurine (83) as a late-stage common intermediate. Compound 83 was readily accessible via previously reported protocols [40], which featured a diastereoselective formal [3 + 3] cycloaddition between 76 and 81 as the key step. This cycloaddition constructs the three contiguous stereocenters and two C–C
Graphical Abstract
Scheme 1: a) The mechanism of Norrish type II reaction and Norrish–Yang cyclization; b) The mechanism of the ...
Scheme 2: Total synthesis of (+)-cyclobutastellettolide B.
Scheme 3: Norrish–Yang cyclization and 1,2-methyl migration.
Scheme 4: Synthetic study toward phainanoids.
Scheme 5: a) Mitsunobu reaction of the C9 ketal; b) Norrish–Yang cyclization of the saturated C5–C6; c) calcu...
Scheme 6: Total synthesis of avarane-type meroterpenoids.
Scheme 7: Total synthesis of gracilisoid A.
Scheme 8: Divergent total synthesis of gracilisoids B–I.
Scheme 9: Mechanism of the late-stage biomimetic photooxidation.
Scheme 10: Asymmetric total synthesis of lycoplatyrine A.
Scheme 11: Photoreaction of pyrrolidine-derived phenyl keto amide.
Scheme 12: Photoredox reactions of naphthoquinones.
Scheme 13: Synthetic study toward γ-rubromycin.
Scheme 14: Substituent-dependent conformational preferences.
Scheme 15: Total synthesis of preussomerins EG1, EG2, and EG3.
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
- photoenzymatic transformation developed by the Hyster group, α-chloroamides were converted to enantioenriched 5-, 6-, 7-, and 8-membered lactams through an enantioselective radical cyclization followed by a diastereoselective HAT, producing contiguous stereocenters [75]. In the subsequent year, the same group
Graphical Abstract
Figure 1: Methods of radical generation (A) and general types of radical reactions (B).
Figure 2: Chiral catalysis in enantioselective radical chemistry [13-37].
Scheme 1: Diastereo- and enantioselective additions of nucleophilic radicals to N-enoyloxazolidinone and pyrr...
Scheme 2: Organocatalyzed formal [3 + 2] cycloadditions affording substituted pyrrolidines.
Scheme 3: Synthesis of a hexacyclic compound via an organocatalyzed enantioselective polyene cyclization.
Scheme 4: Nickel-catalyzed asymmetric cross-coupling reactions.
Scheme 5: Chiral cobalt–porphyrin metalloradical-catalyzed radical cyclization reactions.
Scheme 6: Enantioselective radical chaperone catalysis.
Scheme 7: Enantioselective radical addition by decatungstate/iminium catalysis.
Scheme 8: An ene-reductase-catalyzed photoenzymatic enantioselective radical cyclization/enantioselective HAT...
Scheme 9: Photoenzymatic oxidative C(sp3)–C(sp3) coupling reactions between organoboron compounds and amino a...
Scheme 10: Electrochemical α-alkenylation reactions of 2-acylimidazoles catalyzed by a chiral-at-rhodium Lewis...
Scheme 11: Regio- and enantioselective electrochemical reactions of silyl polyenolates catalyzed by a chiral n...
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
Graphical Abstract
Figure 1: C2–C6 biobased carbonyl building blocks.
Scheme 1: Proposed (2 + 2) route to glycolaldehyde and glycolic acid from erythritol by Cu/AC catalyst (AC = ...
Scheme 2: Reductive amination of GCA.
Scheme 3: N-Formylation of secondary amines by reaction with GCA.
Scheme 4: Synthesis and conversion of hydroxy acetals to cyclic acetals.
Scheme 5: Synthesis of 3-(indol-3-yl)-2,3-dihydrofurans via three-component reaction of glycolaldehyde, indol...
Scheme 6: BiCl3-catalyzed synthesis of benzo[a]carbazoles from 2-arylindoles and α-bromoacetaldehyde ethylene...
Scheme 7: Cu/NCNSs-based conversion of glycerol to glycolic acid and other short biobased acids.
Scheme 8: E. coli-based biotransformation of C1 source molecules (CH4, CO2 and CO) towards C2 glycolic acid.
Scheme 9: N-Formylation of amines with C2 (a) or C3 (b) biomass-based feedstocks.
Scheme 10: Methods for the formation of propanoic acid (PA) from lactic acid (LA).
Scheme 11: Co-polymerization of biobased lactic acid and glycolic acid via a bicatalytic process.
Scheme 12: Oxidation of α-hydroxy acids by tetrachloroaurate(III) in acetic acid–sodium acetate buffer medium.
Figure 2: Selective catalytic pathways for the conversion of lactic acid (LA).
Scheme 13: Synthesis of 1,3-PDO via cross-aldol reaction between formaldehyde and acetaldehyde to 3-hydroxypro...
Scheme 14: Hydrothermal conversion of 1,3-dihydroxy-2-propane and 2,3-dihydroxypropanal to methylglyoxal.
Scheme 15: FLS-catalyzed formose reaction to synthesize GA and DHA.
Scheme 16: GCA and DHA oxidation products of glycerol and isomerization of GCA to DHA under flow conditions us...
Scheme 17: Acid-catalyzed reactions of DHA with alcohols.
Scheme 18: Synthesis of dihydroxyacetone phosphate from dihydroxyacetone.
Scheme 19: Bifunctional acid–base catalyst DHA conversion into lactic acid via pyruvaldehyde or fructose forma...
Scheme 20: Catalytic one-pot synthesis of GA and co-synthesis of formamides and formates from DHA.
Scheme 21: (a) Synthesis of furan derivatives and (b) synthesis of thiophene derivative by cascade [3 + 2] ann...
Scheme 22: Brønsted acidic ionic liquid catalyzed synthesis of benzo[a]carbazole from renewable acetol and 2-p...
Scheme 23: Asymmetric hydrogenation of α-hydroxy ketones to 1,2-diols.
Scheme 24: Synthesis of novel 6-(substituted benzylidene)-2-methylthiazolo [2,3-b]oxazol-5(6H)-one from 1-hydr...
Scheme 25: ʟ-Proline-catalyzed synthesis of anti-diols from hydroxyacetone and aldehydes.
Scheme 26: C–C-bond-formation reactions of a biomass-based feedstock aromatic aldehyde (C5) and hydroxyacetone...
Scheme 27: Ethanol upgrading to C4 bulk chemicals via the thiamine (VB1)-catalyzed acetoin condensation.
Scheme 28: One-pot sequential chemoenzymatic synthesis of 2-aminobutane-1,4-diol and 1,2,4-butanetriol via 1,4...
Scheme 29: Synthesis of 1,4-dihydroxybutan-2-one by microbial transformation.
Scheme 30: Conversion of polyols by [neocuproine)Pd(OAc)]2(OTf)2] to α-hydroxy ketones.
Scheme 31: Chemoselective oxidation of alcohols with chiral palladium-based catalyst 2.
Scheme 32: Electrochemical transformation of furfural to 5-hydroxy-2(5H)-furanone (HFO).
Scheme 33: Selective hydrodeoxygenation of HFO and oxidation to γ-butyrolactone (GBL).
Scheme 34: Photosensitized oxygenation of furan towards HFO via ozonide intermediates.
Scheme 35: Conversion of furfural to HFO and MAN by using mesoporous carbon nitride (SGCN) as photocatalyst.
Scheme 36: Synthesis of HFO from furan derivatives.
Scheme 37: Photooxidation of furfural to 5-hydroxy-2(5H)-furanone (HFO).
Scheme 38: Synthesis of Friedel–Crafts indole adduct from HFO.
Scheme 39: Conversion of HFO to α,γ-substituted chiral γ-lactones.
Scheme 40: Tautomeric transformation of HFO to formylacrylic acid.
Scheme 41: Hydrolysis of HFO to succinic acid in aqueous solution.
Scheme 42: Substitution and condensation reactions of 5-hydroxy-2(5H)-furanone (HFO).
Scheme 43: (a) Conversion of HFO towards valuable C4 chemicals and (b) anodic oxidation of 5-hydroxy-2(5H)-fur...
Figure 3: Conversion of HFO towards other natural and synthetic substances.
Scheme 44: Conversion of furfural to maleic anhydride (reaction a: VOx/Al2O3; reaction b: VPO).
Scheme 45: Conversion of furfural into succinic acid.
Scheme 46: Electro‑, photo‑, and biocatalysis for one-pot selective conversions of furfural into C4 chemicals.
Scheme 47: Production route of furfural from hemicellulose.
Scheme 48: Mechanism for xylose dehydration to furfural through a choline xyloside intermediate.
Scheme 49: Conversion of furfural to furfuryl alcohol and its derivatives.
Scheme 50: Conversion of furfural to furfuryl alcohol and 3-(2-furyl)acrolein.
Scheme 51: The aerobic oxidative condensation of biomass-derived furfural and linear alcohols.
Scheme 52: The single-step synthesis of 2-pentanone from furfural.
Scheme 53: Electrocatalytic coupling reaction of furfural and levulinic acid.
Scheme 54: Conversion of furfural to m-xylylenediamine.
Scheme 55: Conversion of furfural to tetrahydrofuran-derived amines.
Scheme 56: Formation of trans-4,5-diamino-cyclopent-2-enones from furfural.
Scheme 57: Production of pyrrole and proline from furfural.
Scheme 58: Synthesis of 1‑(trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones from furfural.
Scheme 59: Conversion of furfural to furfural-derived diacids.
Scheme 60: A telescope protocol derived from furfural and glycerol.
Scheme 61: A tandem cyclization of furfural and 5,5-dimethyl-1,3-cyclohexanedione.
Scheme 62: A Ugi four-component reaction to construct furfural-based polyamides.
Scheme 63: One-pot synthesis of γ-acyloxy-Cy7 from furfural.
Scheme 64: Dimerization–Piancatelli sequence toward humins precursors from furfural.
Scheme 65: Conversion of furfural to CPN.
Scheme 66: Synthesis of jet fuels range cycloalkanes from CPN and lignin-derived vanillin.
Scheme 67: Solar-energy-driven synthesis of high-density biofuels from CPN.
Scheme 68: Reductive amination of CPN to cyclopentylamine.
Scheme 69: Asymmetric hydrogenation of C=O bonds of exocyclic α,β-unsaturated cyclopentanones.
Scheme 70: Preparation of levulinic acid via the C5 route (route a) or C6 route (routes b1 and b2).
Scheme 71: Mechanism of the rehydration of HMF to levulinic acid and formic acid.
Scheme 72: Important levulinic acid-derived chemicals.
Scheme 73: Direct conversion of levulinic acid to pentanoic acid.
Scheme 74: Catalytic aerobic oxidation of levulinic acid to citramalic acid.
Scheme 75: Conversion of levulinic acid to 1,4-pentanediol (a) see ref. [236]; b) see ref. [237]; c) see ref. [238]; d) see r...
Scheme 76: Selective production of 2-butanol through hydrogenolysis of levulinic acid.
Scheme 77: General reaction pathways proposed for the formation of 5MPs from levulinic acid.
Scheme 78: Selective reductive amination of levulinic acid to N-substituted pyrroles.
Scheme 79: Reductive amination of levulinic acid to chiral pyrrolidinone.
Scheme 80: Reductive amination of levulinic acid to non-natural chiral γ-amino acid.
Scheme 81: Nitrogen-containing chemicals derived from levulinic acid.
Scheme 82: Preparation of GVL from levulinic acid by dehydration and hydrogenation.
Scheme 83: Ruthenium-catalyzed levulinic acid to chiral γ-valerolactone.
Scheme 84: Catalytic asymmetric hydrogenation of levulinic acid to chiral GVL.
Scheme 85: Three steps synthesis of ε-caprolactam from GVL.
Scheme 86: Multistep synthesis of nylon 6,6 from GVL.
Scheme 87: Preparation of MeGVL by α-alkylation of GVL.
Scheme 88: Ring-opening polymerization of five-membered lactones.
Scheme 89: Synthesis of GVL-based ionic liquids.
Scheme 90: Preparation of butene isomers from GVL under Lewis acid conditions.
Scheme 91: Construction of C5–C12 fuels from GVL over nano-HZSM-5 catalysts.
Scheme 92: Preparation of alkyl valerate from GVL via ring opening/reduction/esterification sequence.
Scheme 93: Construction of 4-acyloxypentanoic acids from GVL.
Scheme 94: Synthesis of 1,4-pentanediol (PDO) from GVL.
Scheme 95: Construction of novel cyclic hemiketal platforms via self-Claisen condensation of GVL.
Scheme 96: Copper-catalyzed lactamization of GVL.
Figure 4: Main scaffolds obtained from HMF.
Scheme 97: Biginelli reactions towards HMF-containing dihydropyrimidinones.
Scheme 98: Hantzsch dihydropyridine synthesis involving HMF.
Scheme 99: The Kabachnik–Fields reaction involving HMF.
Scheme 100: Construction of oxazolidinone from HMF.
Scheme 101: Construction of rhodamine-furan hybrids from HMF.
Scheme 102: A Groebke–Blackburn–Bienaymé reaction involving HMF.
Scheme 103: HMF-containing benzodiazepines by [4 + 2 + 1] cycloadditions.
Scheme 104: Synthesis of fluorinated analogues of α-aryl ketones.
Scheme 105: Synthesis of HMF derived disubstituted γ-butyrolactone.
Scheme 106: Functionalized aromatics from furfural and HMF.
Scheme 107: Diels–Alder adducts from HMF or furfural with N-methylmaleimide.
Scheme 108: Pathway of the one-pot conversion of HMF into phthalic anhydride.
Scheme 109: Photocatalyzed preparation of humins (L-H) from HMF mixed with spoiled HMF residues (LMW-H) and fur...
Scheme 110: Asymmetric dipolar cycloadditions on HMF.
Scheme 111: Dipolar cycloadditions of HMF based nitrones to 3,4- and 3,5-substituted isoxazolidines.
Scheme 112: Production of δ-lactone-fused cyclopenten-2-ones from HMF.
Scheme 113: Aza-Piancatelli access to aza-spirocycles from HMF-derived intermediates.
Scheme 114: Cross-condensation of furfural, acetone and HMF into C13, C14 and C15 products.
Scheme 115: Base-catalyzed aldol condensation/dehydration sequences from HMF.
Scheme 116: Condensation of HMF and active methylene nitrile.
Scheme 117: MBH reactions involving HMF.
Scheme 118: Synthesis of HMF-derived ionic liquids.
Scheme 119: Reductive amination/enzymatic acylation sequence towards HMF-based surfactants.
Scheme 120: The formation of 5-chloromethylfurfural (CMF).
Scheme 121: Conversion of CMF to HMF, levulinic acid, and alkyl levulinates.
Scheme 122: Conversion of CMF to CMFCC and FDCC.
Scheme 123: Conversion of CMF to BHMF.
Scheme 124: Conversion of CMF to DMF.
Scheme 125: CMF chlorine atom substitutions toward HMF ethers and esters.
Scheme 126: Introduction of carbon nucleophiles in CMF.
Scheme 127: NHC-catalyzed remote enantioselective Mannich-type reactions of CMF.
Scheme 128: Conversion of CMF to promising biomass-derived dyes.
Scheme 129: Radical transformation of CMF with styrenes.
Scheme 130: Synthesis of natural herbicide δ-aminolevulinic acid from CMF.
Scheme 131: Four step synthesis of the drug ranitidine from CMF.
Scheme 132: Pd/CO2 cooperative catalysis for the production of HHD and HXD.
Scheme 133: Different ruthenium (Ru) catalysts for the ring-opening of 5-HMF to HHD.
Scheme 134: Proposed pathways for preparing HXD from HMF.
Scheme 135: MCP formation and uses.
Scheme 136: Cu(I)-catalyzed highly selective oxidation of HHD to 2,5-dioxohexanal.
Scheme 137: Synthesis of N‑substituted 3‑hydroxypyridinium salts from 2,5-dioxohexanal.
Scheme 138: Ru catalyzed hydrogenations of HHD to 1,2,5-hexanetriol (a) see ref. [396]; b) see ref. [397]).
Scheme 139: Aviation fuel range quadricyclanes produced by HXD.
Scheme 140: Synthesis of HDGK from HXD and glycerol as a chain extender.
Scheme 141: Synthesis of serinol pyrrole from HXD and serinol.
Scheme 142: Synthesis of pyrroles from HXD and nitroarenes.
Scheme 143: Two-step production of PX from cellulose via HXD.
Scheme 144: Preparation of HCPN from HMF via hydrogenation and ring rearrangement.
Scheme 145: Suggested pathways from HMF to HCPN.
Scheme 146: α-Alkylation of HCPN with ethylene gas.
Scheme 147: Synthesis of 3-(hydroxymethyl)cyclopentylamine from HMF via reductive amination of HCPN.
Scheme 148: Production of LGO and Cyrene® from biomass.
Scheme 149: Synthesis of HBO from LGO and other applications.
Scheme 150: Construction of m-Cyrene® homopolymer.
Scheme 151: Conversion of Cyrene® to THFDM and 1,6-hexanediol.
Scheme 152: RAFT co-polymerization of LGO and butadienes.
Scheme 153: Polycondensation of HO-LGOL and diols with dimethyl adipate.
Scheme 154: Self-condensation of Cyrene® and Claisen–Schmidt reactions.
Scheme 155: Synthesis of 5-amino-2-(hydroxymethyl)tetrahydropyran from Cyrene®.
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
- -workers [21], its synthesis has attracted attention of the synthetic community. The group of Snider [47], Evano [48][49], and Papeo [50] reported several elegant highly enantio- and diastereoselective total syntheses of this alkaloid from ᴅ-tryptophan. With our longstanding interest in the efficient total
Graphical Abstract
Figure 1: Structures of some reported chaetominine-type alkaloids and revised structures via our total synthe...
Scheme 1: Improved total synthesis of (–)-isochaetominine A (4) and diastereomer 16.
Scheme 2: Diastereoconvergent transformations of 17 and 18 into two diastereomers of versiquinazoline H.
Scheme 3: Mono- and double epimerization-based enantiodivergent syntheses of chaetominine-type alkaloids and ...
Scheme 4: Enantioselective synthesis of the proposed structure of aspera chaetominine A.
Scheme 5: Enantioselective syntheses of both the proposed and revised structures of aspera chaetominine B.
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
- The retrosynthetic analysis of tricyclic-PGDM methyl ester 4 is shown in Scheme 2. We expected to derive 4 from tricyclic substrate 12 via a side-chain installation at C8 [22]. The spiroketal moiety in compound 12 could be obtained from compound 13 via a diastereoselective spiroketalization dictated
- by the anomeric effect [23] in the tricyclic scaffold. Compound 13 could be produced from olefin 14 via cross-metathesis. The regio- and diastereoselective connection of C8 and C12 in compound 14 could be realized through a transition-metal-mediated oxidative radical cyclization through TS-1 from β
- 4 was expected to be derived from tricyclic substrate 26 via a Z-selective cross-metathesis [9]. The allyl group in compound 26 could be installed in β-keto ester 21 via sequential transesterification [33] and palladium-catalyzed decarboxylative allylation [32]. The regio- and diastereoselective
Graphical Abstract
Scheme 1: Representative prostaglandins and general synthetic strategy toward PGDM methyl ester 4.
Scheme 2: Retrosynthetic analysis for the first generation synthesis of PGDM methyl ester 4.
Scheme 3: Synthesis of bicyclic ketal 25.
Scheme 4: Retrosynthetic analysis for the second-generation synthesis of tricyclic PGDM methyl ester 4.
Scheme 5: Asymmetric total synthesis of tricyclic-PGDM methyl ester 4.
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
- , ligand 205a proved to be suitable for 2-ethylpropane-1,3-diol (204). A three-step sequence then furnished enone 207, which underwent diastereoselective aldol reaction with fragment 208 to give compound 209. Alkyne 210, prepared from 209 in six steps, underwent addition with fragment 211 to yield compound
Graphical Abstract
Scheme 1: General mechanism of a lipase-catalyzed esterification.
Scheme 2: Shishido’s synthesis of (−)-xanthorrhizol (4) and (+)-heliannuol D (8).
Scheme 3: Shishido’s synthesis of a) (−)-heliannuol A (15) and b) heliannuol G (20) and heliannuol H (21).
Scheme 4: Deska’s synthesis of hyperione A (30) and ent-hyperione B (31).
Scheme 5: Huang’s synthesis of (+)-brazilin (37).
Scheme 6: Shishido’s synthesis of (−)-heliannuol D (42) and (+)-heliannuol A (43).
Scheme 7: Chênevert’s synthesis of (S)-α-tocotrienol (49).
Scheme 8: Kita’s synthesis of monoester 53.
Scheme 9: Kita’s synthesis of fredericamycin A (60).
Scheme 10: Takabe’s synthesis of (E)-3,7-dimethyl-2-octene-1,8-diol (64).
Scheme 11: Takabe’s synthesis of (18S)-variabilin (70).
Scheme 12: Kawasaki’s synthesis of (S)-Rosaphen (74) and (R)-Rosaphen (75).
Scheme 13: Tokuyama’s synthesis of a) (−)-petrosin (84) and b) (+)-petrosin (86).
Scheme 14: Fukuyama’s synthesis of leustroducsin B (96).
Scheme 15: Nanda’s synthesis of a) fragment 100, b) fragment 106 and c) (−)-rasfonin (109).
Scheme 16: Davies’ synthesis of (+)-pilocarpine (115) and (+)-isopilocarpine (116).
Scheme 17: Ōmura’s synthesis of salinosporamide A (125).
Scheme 18: Kang’s synthesis of ʟ-cladinose (124) and its derivative.
Scheme 19: Kang’s preparation of fragment 139.
Scheme 20: Kang’s synthesis of azithromycin (149).
Scheme 21: Kang’s synthesis of (−)-dysiherbaine (156).
Scheme 22: Kang’s synthesis of (−)-kaitocephalin (166).
Scheme 23: Kang’s synthesis of laidlomycin (180).
Scheme 24: Snyder’s synthesis of arboridinine (190).
Scheme 25: Ma’s synthesis of (+)-alstrostine G (203).
Scheme 26: Trost’s synthesis of (−)-18-epi-peloruside A (215).
Scheme 27: Lindel’s synthesis of (–)-dihydroraputindole (223).
Scheme 28: Iwata’s synthesis of a) (−)-talaromycin B (232) and b) (+)-talaromycin A (235).
Scheme 29: Cook’s synthesis of a) (−)-vincamajinine (240) and b) (−)-11-methoxy-17-epivincamajine (245).
Scheme 30: Cook’s synthesis of (+)-dehydrovoachalotine (249) and voachalotine (250).
Scheme 31: Cook’s synthesis of a) (−)-12-methoxy-Nb-methylvoachalotine (257) and b) (+)-polyneuridine, macusin...
Scheme 32: Trauner’s synthesis of stephadiamine (273).
Scheme 33: Garg’s synthesis of (–)-ψ-akuammigine (285).
Scheme 34: Ding’s synthesis of (+)-18-benzoyldavisinol (293) and (+)-davisinol (294).
Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity
- Madara Darzina,
- Anna Lielpetere and
- Aigars Jirgensons
Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136
- reactions. Out of these, the aza-Diels–Alder reaction with TsNCO was successful, leading to a highly diastereoselective formation of an oxazolo[3,2-c]pyrimidine derivative. Keywords: aza-Diels–Alder reaction; electrosynthesis; furfural; valinol; vinyloxazoline; Introduction The utilization of biomass as
- to form oxazolo[3,2-c]pyrimidine derivative 7 (Scheme 7). The highly diastereoselective formation of product 7 can be explained based on the theoretical calculations by Elliott et al. of aza-Diels–Alder reaction of vinyloxazoline with TsNCO [19]. According to their investigations, the aza-nucleophile
Graphical Abstract
Scheme 1: Proposed approach for the preparation of vinyloxazoline 6.
Scheme 2: Synthesis of furfuryl amino alcohols S-2d and R-2d and their electrochemical oxidation to esters S-...
Scheme 3: Cleavage of the N-Alloc group leading to a mixture of isomers cis-S-5 and trans-S-5.
Scheme 4: Cleavage of the N-Alloc group with PdCl2(S-BINAP) leading to trans-S-5 and trans-R-5.
Scheme 5: Cyclization of amides trans-S-5 and trans-R-5 to oxazolines S-6 and R-6.
Scheme 6: aza-Diels–Alder reaction of vinyloxazoline S-6 with TsNCO.
Scheme 7: The proposed mechanism of product 7 formation.
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
- 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
Graphical Abstract
Figure 1: Pyruvylated galactose on bacterial polysaccharides PS A1 (1), 1.15 EPS (2) and Rhizobium leguminosa...
Figure 2: (a) Oak Ridge Thermal Ellipsoid Plot view of the X-ray crystal structure of pyruvylated galactose 6...
Scheme 1: Synthesis of trisaccharide precursor 14.
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
Graphical Abstract
Figure 1: Bond lengths and bond angles in oxetane at 140 K [2].
Figure 2: Analogy of 3-substituted oxetanes to carbonyl and gem-dimethyl groups [12].
Figure 3: Use of oxetanes in drug design – selected examples.
Figure 4: Examples of oxetane-containing natural products.
Scheme 1: Synthetic strategies towards construction of the oxetane ring.
Scheme 2: Overview of intramolecular Williamson etherification and competing Grob fragmentation.
Scheme 3: Synthesis of spiro-oxetanes via 1,4-C–H insertion and Williamson etherification.
Scheme 4: Use of phenyl vinyl selenone in the synthesis of spirooxindole oxetanes.
Scheme 5: Synthesis of bicyclic 3,5-anhydrofuranoses via double epoxide opening/etherification.
Scheme 6: Preparation of spirooxetanes by cycloisomerisation via MHAT/RPC.
Scheme 7: Oxetane synthesis via alcohol C–H functionalisation.
Scheme 8: Access to oxetanes 38 from α-acetyloxy iodides.
Scheme 9: The kilogram-scale synthesis of oxetane intermediate 41.
Scheme 10: Overview of the intramolecular opening of 3-membered rings.
Scheme 11: Synthesis of 4,7-dioxatricyclo[3.2.1.03,6]octane skeletons.
Scheme 12: Silicon-directed electrophilic cyclisation of homoallylic alcohols.
Scheme 13: Hydrosilylation–iodocyclisation of homopropargylic alcohols.
Scheme 14: Cu-catalysed intramolecular O-vinylation of γ-bromohomoallylic alcohols.
Scheme 15: Cu-catalysed intramolecular cross-coupling of hydroxyvinylstannanes.
Scheme 16: Isomerisation of oxiranyl ethers containing weakly carbanion-stabilising groups.
Scheme 17: Cyclisation of diethyl haloalkoxymalonates.
Scheme 18: Synthesis of oxetanes through a 1,5-HAT/radical recombination sequence.
Scheme 19: General approach to oxetanes via [2 + 2] cycloadditions.
Scheme 20: Synthesis of tricyclic 4:4:4 oxetanes through a photochemical triple cascade reaction.
Scheme 21: Iridium-catalysed Paternò–Büchi reaction between α-ketoesters and simple alkenes.
Scheme 22: Three-step synthesis of spirocyclic oxetanes 83 via Paternò–Büchi reaction, nucleophilic ring openi...
Scheme 23: Enantioselective Paternò–Büchi reaction catalysed by a chiral iridium photocatalyst.
Scheme 24: Synthesis of polysubstituted oxetanes 92 via Cu(II)-mediated formal [2 + 2] cycloadditions.
Scheme 25: Synthesis of alkylideneoxetanes via NHC- and DBU-mediated formal [2 + 2] cycloadditions.
Scheme 26: Use of sulphur-stabilised carbanions in ring expansions.
Scheme 27: Synthesis of α,α-difluoro(arylthio)methyl oxetanes.
Scheme 28: Ring expansion in an industrial synthesis of PF-06878031.
Scheme 29: Ring contraction of triflated 2-hydroxy-γ-lactones.
Scheme 30: Ring contraction in an industrial synthesis of PF-06878031.
Scheme 31: Photochemical ring contraction of 2,5-dihydrofurans by aryldiazoacetic acid esters.
Scheme 32: Synthesis of 3-oxetanones via O-H insertion of carbenes.
Scheme 33: Synthesis of phosphonate oxetanones via gold-mediated alkyne oxidation/O–H insertion.
Scheme 34: Syntheses and common derivatisations of 3-oxetanone.
Scheme 35: SN1 substitution of 3-aryloxetan-3-ols by thiols and alcohols.
Scheme 36: Fe–Ni dual-catalytic olefin hydroarylation towards 3-alkyl-3-(hetero)aryloxetanes.
Scheme 37: Synthesis of 3-aryloxetan-3-carboxylic acids.
Scheme 38: Decarboxylative alkylation of 3-aryloxetan-3-carboxylic acids.
Scheme 39: Synthesis of 3-amino-3-aryloxetanes via photoredox/nickel cross-coupling catalysis.
Scheme 40: Intermolecular cross-selective [2 + 2] photocycloaddition towards spirooxetanes.
Scheme 41: Synthesis of 3-aryl-3-aminooxetanes via defluorosulphonylative coupling.
Scheme 42: Two-step synthesis of amide bioisosteres via benzotriazolyl Mannich adducts 170.
Scheme 43: Functionalisation of oxetanyl trichloroacetimidates 172.
Scheme 44: Synthesis of oxetane-amino esters 176.
Scheme 45: Tandem Friedel–Crafts alkylation/intramolecular ring opening of 3-aryloxetan-3-ols.
Scheme 46: Synthesis of polysubstituted furans and pyrroles.
Scheme 47: Synthesis of oxazolines and bisoxazolines.
Scheme 48: Tandem, one-pot syntheses of various polycyclic heterocycles.
Scheme 49: Synthesis of 1,2-dihydroquinolines via skeletal reorganisation of oxetanes.
Scheme 50: Synthesis of benzoindolines and 2,3-dihydrobenzofurans and their derivatisations.
Scheme 51: Synthesis of polysubstituted 1,4-dioxanes.
Scheme 52: Preparation of various lactones via ring opening of oxetane-carboxylic acids 219.
Scheme 53: Tsuji-Trost allylation/ring opening of 3-aminooxetanes.
Scheme 54: Arylative skeletal rearrangement of 3-vinyloxetan-3-ols to 2,5-dihydrofurans.
Scheme 55: Reductive opening of oxetanes using catalytic Mg–H species.
Scheme 56: Opening of oxetanes by silyl ketene acetals.
Scheme 57: Rhodium-catalysed hydroacylation of oxetanes.
Scheme 58: Generation of radicals from oxetanes mediated by a vitamin B12-derived cobalt catalyst.
Scheme 59: Reductive opening of oxetanes by B–Si frustrated Lewis pairs.
Scheme 60: Zirconocene-mediated reductive opening of oxetanes.
Scheme 61: Enantioselective syntheses of small and medium-size rings using chiral phosphoric acids.
Scheme 62: Asymmetric synthesis of 2,3-dihydrobenzo[b]oxepines catalysed by a chiral scandium complex.
Scheme 63: Enantioselective synthesis of 1,3-bromohydrins under a chiral squaramide catalysis.
Scheme 64: Enantioselective opening of 2-aryl-2-ethynyloxetanes by anilines.
Scheme 65: Ru-catalysed insertion of diazocarbonyls into oxetanes.
Scheme 66: Ring expansion of oxetanes by stabilised carbenes generated under blue light irradiation.
Scheme 67: Expansion of oxetanes via nickel-catalysed insertion of alkynyltrifluoroborates.
Scheme 68: Nickel-catalysed expansion of oxetanes into ε-caprolactones.
Scheme 69: Expansion of oxetanes via cobalt-catalysed carbonyl insertion.
Scheme 70: Gold-catalysed intramolecular 1,1-carboalkoxylation of oxetane-ynamides.
Scheme 71: Expansion of oxetanes by stabilised sulphoxonium ylides.
Scheme 72: Cu-catalysed ring expansion of 2-vinyloxetanes by diazoesters.
Scheme 73: Total synthesis of (+)-oxetin.
Scheme 74: Total synthesis of racemic oxetanocin A.
Scheme 75: Total synthesis of (−)-merrilactone A.
Scheme 76: Total synthesis of (+)-dictyoxetane.
Scheme 77: Total synthesis of ent-dichrocephone B.
Scheme 78: Total synthesis of (−)-mitrephorone A.
Scheme 79: Total synthesis of (−)-taxol.
Correction: Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates
- Deepa Nair,
- Abhishek Tiwari,
- Banamali Laha,
- Lakshminarayana Satham and
- Irishi N. N. Namboothiri
Beilstein J. Org. Chem. 2025, 21, 1170–1170, doi:10.3762/bjoc.21.93
- Deepa Nair Abhishek Tiwari Banamali Laha Lakshminarayana Satham Irishi N. N. Namboothiri Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India 10.3762/bjoc.21.93 Keywords: arylidenemalonates; curcumins; cyclohexanones; diastereoselective synthesis; Michael
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
- presence of pivaloyl chloride, triethylamine, and lithium chloride to produce compound 71 in 86% yield. Diastereoselective methylation of 71 was achieved by treating it with NaHMDS at low temperature, followed by the addition of methyl iodide, resulting in a diastereomeric ratio greater than 98:2
Graphical Abstract
Figure 1: Chemical structure of borrelidin (1).
Scheme 1: Synthetic strategy for Morken’s C2–C12 intermediate 20 as reported by Uguen et al. [41].
Scheme 2: Preparation of monoacetates 37 and ent-38 by Uguen et al. [41].
Scheme 3: Preparation of sulfones 27 and ent-27 by Uguen et al. [41].
Scheme 4: Attempts to couple sulfones 27 and ent-27 with epoxides 23a–c reported by Uguen et al. [41].
Scheme 5: Modified synthetic plan for Morken’s C2–C12 intermediate by Uguen [41].
Scheme 6: Revised synthetic strategy for Morken’s C2–C12 intermediate 20 by Uguen [41].
Scheme 7: Iterative synthesis of polydeoxypropionates developed by Zhou et al. [40].
Scheme 8: Application of iterative synthesis of polydeoxypropionate to construct the C3–C11 fragment 60 of bo...
Scheme 9: Retrosynthetic analysis of borrelidin by Yadav et al. [39].
Scheme 10: Two-carbon homologation of precursor 66 in the synthesize C1–C11 fragment 61 of borrelidin [39].
Scheme 11: Synthesis of the C1–C11 fragment 61 of borrelidin from monoalcohol 65 [39].
Scheme 12: Synthetic plan for Theodorakis’ C3–C11 fragment 82 of borrelidin by Laschat et al. [38].
Scheme 13: Synthesis of Theodorakis’ C3–C11 fragment 82 from compound 88 [38].
Scheme 14: Retrosynthesis of 61 and 62b by Minnaard and Madduri [37].
Scheme 15: Synthesis of intermediate 98 by Minnaard and Madduri [37].
Scheme 16: Synthesis of Ōmura’s C1–C11 fragment 61 by Minnaard and Madduri [37].
Scheme 17: Synthesis of fragment 62b of borrelidin as proposed by Minnaard and Madduri [37].
Scheme 18: Iterative directed allylation for the synthesis of deoxypropionates by Herber and Breit [33].
Scheme 19: Iterative copper-mediated directed allyl substitution for the synthesis of Theodorakis’ C3–C11 frag...
Scheme 20: Retrosynthesis of the C3–C17 fragment of borrelidin by Iqbal and co-workers [35].
Scheme 21: Synthesis of key intermediates 137 and 147 for the synthesis of the C3–C17 fragment of borrelidin.
Scheme 22: Synthesis of the C3–C17 fragment 150a,b of borrelidin.
Scheme 23: Synthesis of the C11–C15 fragment 155a of borrelidin.
Scheme 24: Macrocyclization of borrelidin model compounds 155a and 155b using ring-closing metathesis.
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
- , the terminal alkene remains intact during this process, and the initial protonation proceeds with full stereocontrol, rendering this transformation both highly chemo- and diastereoselective. From the cyclization result, it is presumed that the higher nucleophilicity of the alkyne functionality over
- total synthesis of cephalotaxine. Similarly, diastereoselective reduction of 25 with KBH4 followed by alane reduction provided another alkaloid cephalezomine H. Collective total syntheses of Cephalotaxus alkaloids The cyclopentane ring in most Cephalotaxus alkaloids is characterized by the highest
Graphical Abstract
Figure 1: Reactivity of enamides and enamide cyclizations.
Scheme 1: Total synthesis of (−)-dihydrolycopodine and (−)-lycopodine.
Scheme 2: Collective total synthesis of fawcettimine-type alkaloids.
Scheme 3: Total syntheses of cephalotaxine and cephalezomine H.
Scheme 4: Collective total syntheses of Cephalotaxus alkaloids.
Scheme 5: Asymmetric tandem cyclization/Pictet–Spengler reaction of tertiary enamides.
Scheme 6: Tandem cyclization/Pictet–Spengler reaction for the synthesis of chiral tetracyclic compounds.
Scheme 7: Total synthesis of (−)-cephalocyclidin A.
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
- ring was opened in a diastereoselective (SN2 type) and exo-selective manner by a trifluoroacetate anion. The trifluoroacetate anion was conveniently derived from (bis(trifluoroacetoxy)iodo)benzene (PIFA), which was used as the stoichiometric oxidant in the reaction. Overall, this amounted to a highly
- regioselective, diastereoselective, and metal-free protocol for alkene amino-hydroxylation, which compared favorably to prior art in this area [25][26][27][28][29][30][31][32]. Naturally, we wondered if other O-nucleophiles were competent in the ring-opening of the aziridinium intermediate. Indeed, almost all
Graphical Abstract
Scheme 1: Existing reports of intramolecular alkene functionalization reactions with nitreniums have focused ...
Figure 1: Poor performers.
Scheme 2: Putative reaction mechanism.
Scheme 3: (A) Scale-up and (B) applications.
A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids
- Zhiyang Zhang,
- Jialei Hu,
- Hanfeng Ding,
- Li Zhang and
- Peirong Rao
Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75
- from α-iodoenone 13. Our synthesis began with the preparation of α-iodoenone 13 (Scheme 2). The α-monomethylation of cyclohexenone 15 was efficiently carried out with LDA, HMPA, and MeI [37], producing enone 16 in 78% yield. Subsequently, a diastereoselective aldol reaction between 16 and 3-furaldehyde
Graphical Abstract
Figure 1: Representative limonoid triterpenes.
Scheme 1: Structures and retrosynthetic analysis of krishnolides A (7) and C (8).
Scheme 2: Construction of α-iodoenone 13.
Scheme 3: Construction of aldehyde 14.
Scheme 4: Synthesis of the advanced intermediate 10 (in the X ray structure of 10 solvent molecule is omitted...
