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Search for "halogen" in Full Text gives 481 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts
- Kadri Kriis,
- Harry Martõnov,
- Annette Miller,
- Mia Peterson,
- Ivar Järving and
- Tõnis Kanger
Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8
- synthesized and screened in asymmetric Mannich reaction. The reaction of aromatic imines with malonates in the presence of amino acid-derived catalysts gave Mannich adducts in very high enantiomeric purities (up to 98% ee). It is proposed that a network of hydrogen and halogen bonds with Lewis bases, together
- efficient in Mannich reactions, as demonstrated by our studies [18] and those of others [19][20][21]. Halogen bonding has also been introduced to further broaden the field of noncovalent interactions. Despite the limited number of asymmetric transformations driven solely by halogen-bond activation [22
- ], halogen bonding is more frequently employed as a component of multifunctional catalytic systems [23][24][25]. Multifunctionality of the catalyst is essential to intensify weak noncovalent interactions. Results and Discussion As a continuation of our previous studies [18][24], we now report an asymmetric
Graphical Abstract
Scheme 1: The catalytic Mannich reaction under study.
Figure 1: Screened catalysts.
Figure 2: Model for the interaction of the catalyst with the imine.
Figure 3: Substrate scope of the asymmetric Mannich reaction.
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
- (±)-dihydrolysergic acid (Scheme 11). Smith and co-workers recently reported a six-step synthesis of (±)-lysergic acid [77]. In contrast to previous approaches, the pyridine was introduced via a magnesium–halogen exchange of pyridyl iodide 93, followed by addition to aldehyde 94. Subsequent reduction of the resulting
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.
Advances in Zr-mediated radical transformations and applications to total synthesis
- Hiroshige Ogawa and
- Hugh Nakamura
Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3
- for future development. Keywords: halogen atom transfer; photoredox; radical; total synthesis; zirconium; Introduction Zirconium, a transition metal in the same group as titanium, has been employed across research fields and in medical applications owing to its distinctive physical and chemical
- Schwartz’s reagent (Scheme 1) [7][8]. When compound 2, bearing an alkyl halide and an olefin moiety, was treated with triethylborane and Schwartz’s reagent in tetrahydrofuran, a halogen atom transfer (XAT) occurred at the alkyl halide, generating alkyl radical 3. This radical subsequently underwent
- , Schwartz’s reagent reacts with triethylborane to generate a low-valent zirconium complex 5. This complex abstracts the halogen atom from the alkyl halide, forming alkyl radical 8. The radical then cyclizes onto the olefin, and the resulting radical intermediate undergoes hydrogen atom transfer (HAT) from
Graphical Abstract
Figure 1: Historical background of zirconium and its physical properties. Image depicted in the background of ...
Scheme 1: Zr-mediated radical cyclization.
Scheme 2: Ni/Zr-mediated one-pot ketone synthesis.
Scheme 3: Zirconocene-catalyzed alkylative dimerization of 2-methylene-1,3-dithiane.
Scheme 4: Zirconium complexes as a photoredox catalyst.
Scheme 5: Zr-catalyzed reductive ring opening of epoxides.
Scheme 6: Zr-catalyzed reductive ring opening of oxetanes. a10 mol % of Cp2Zr(OTf)2·THF was used. bPhCF3 was ...
Scheme 7: Zr-catalyzed halogen atom transfer of alkyl chlorides.
Scheme 8: Zr-catalyzed radical homo coupling of alkyl chlorides.
Scheme 9: Zr-catalyzed fluorine atom transfer.
Scheme 10: Zr-catalyzed C–O bond cleavage. aYield without the use of P(OEt)3.
Scheme 11: Application to the total synthesis of halichondrins.
Scheme 12: Zr-catalyzed C3 dimerization of 3-bromotryptophan derivatives. aCp2ZrCl2 was used.
Scheme 13: Mechanistic studies.
Scheme 14: Application to the total synthesis of cyctetryptomycins. A photo of compound 61b was taken by the a...
Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene
- Dmitry N. Platonov,
- Alexander Yu. Belyy,
- Rinat F. Salikov,
- Kirill S. Erokhin and
- Yury V. Tomilov
Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2
- chlorine is associated with an increase in energy of the lowest unoccupied molecular orbital of halogen molecules and a decrease in their electrophilicity. Therefore, if an electrophilic mechanism takes place, iodine apparently reacts with the main conformer faster than a transition to conformer 2' may
- possibility of i-halogenation via a chain radical mechanism (Scheme 3). The initiation stage includes an oxidation of anion 2 into the corresponding radical 13 which in turn reacts with halogens to form products 4a,b and a halogen atom which can also oxidize the anion. Quantum chemical calculations revealed
Graphical Abstract
Figure 1: The expected and the unexpected in selected synthetic strategies.
Figure 2: Distortion in antiaromatic hepta- and hexa(methoxycarbonyl)cycloheptatrienyl anions 1 and 2. HOMO (...
Scheme 1: Reactions of anion 2 generated from cycloheptatriene 3 with halogens and alkyl halides.
Scheme 2: Reactions of anion 2 generated from cycloheptatriene 3 with diazonium salts.
Figure 3: Two conformers of hexa(methoxycarbonyl)cycloheptatrienyl anion 2 and 2'. The energies were obtained...
Scheme 3: Radical mechanism for reactions of anion 2 with halogens, suggested structure of trapped product. T...
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
- -catalyzed C–halogen bond formation (Figure 3E) [36]. Exchange reactions were reviewed by Evano and Nitelet in 2018 (Figure 3F) [37]. In 2020, Gandelman and co-workers provided an overview of decarboxylative chlorination reactions of carboxylic acids (Figure 3G) [38]. Hoveyda’s 2023 review highlights
- reported the use of (PhO)3P–halogen-based reagents for the synthesis of alkenyl halides (Scheme 12) [64]. A variety of alkenyl chlorides was obtained in good yields, with functional groups such as esters and boronates well tolerated. When camphor was treated with (PhO)3P·Cl2 (TPPCl2), the two
- Finkelstein-type halide exchange reaction (Scheme 23). This strategy leverages the decreasing bond-dissociation energies across the halogen series – C–Cl (D298(C−Cl) = 395 kJ mol−1) and C–Br (D298(C–Br) = 318 kJ mol−1) bonds compared to the C–I bond (D298(C–I) = 253 kJ mol−1) to drive the substitution of
Graphical Abstract
Figure 1: Representative alkenyl chloride motifs in natural products. References: Pinnaic acid [8], haterumalide ...
Figure 2: Representative alkenyl chloride motifs in pharmaceuticals and pesticides. References: clomifene [25], e...
Figure 3: Graphical overview of previously published reviews addressing the synthesis of alkenyl chlorides.
Figure 4: Classification of synthetic approaches to alkenyl chlorides.
Scheme 1: Early works by Friedel, Henry, and Favorsky.
Scheme 2: Product distribution obtained by H NMR integration of crude compound as observed by Kagan and co-wo...
Scheme 3: Side reactions observed for the reaction of 14 with PCl5.
Scheme 4: Only compounds 15 and 18 were observed in the presence of Hünig’s base.
Scheme 5: Efficient synthesis of dichloride 15 at low temperatures.
Scheme 6: Various syntheses of alkenyl chlorides on larger scale.
Scheme 7: Scope of the reaction of ketones with PCl5 in boiling cyclohexane.
Scheme 8: Side reactions occur when using excess amounts of PCl5.
Scheme 9: Formation of versatile β-chlorovinyl ketones.
Scheme 10: Mixture of PCl5 and PCl3 used for the synthesis of 49.
Scheme 11: Catechol–PCl3 reagents for the synthesis of alkenyl chlorides.
Scheme 12: (PhO)3P–halogen-based reagents for the synthesis of alkenyl halides.
Scheme 13: Preparation of alkenyl chlorides from alkenyl phosphates.
Scheme 14: Preparation of alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 15: Preparation of electron-rich alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 16: Cu-promoted synthesis of alkenyl chlorides from ketones and POCl3.
Figure 5: GC yield of 9 depending on time and reaction temperature.
Figure 6: Broken reaction flask after attempts to clean the polymerized residue.
Figure 7: GC yield of 9 depending on the amount of CuCl and time.
Scheme 17: Treatment of 4-chromanones with PCl3.
Scheme 18: Synthesis of alkenyl chlorides from the reaction of ketones with acyl chlorides.
Scheme 19: ZnCl2-promoted alkenyl chloride synthesis.
Scheme 20: Regeneration of acid chlorides by triphosgene.
Scheme 21: Alkenyl chlorides from ketones and triphosgene.
Scheme 22: Various substitution reactions.
Scheme 23: Vinylic Finkelstein reactions reported by Evano and co-workers.
Scheme 24: Challenge of selective monohydrochlorination of alkynes.
Scheme 25: Sterically encumbered internal alkynes furnish the hydrochlorination products in high yield.
Scheme 26: Recent work by Kropp with HCl absorbed on alumina.
Scheme 27: High selectivities for monhydrochlorination with nitromethane/acetic acid as solvent.
Figure 8: Functionalized alkynes which typically afford the monhydrochlorinated products.
Scheme 28: Related chorosulfonylation and chloroamination reactions.
Scheme 29: Reaction of organometallic reagents with chlorine electrophiles.
Scheme 30: Elimination reactions of dichlorides to furnish alkenyl chlorides.
Scheme 31: Elimination reactions of allyl chloride 182 to furnish alkenyl chloride 183.
Scheme 32: Detailed studies by Schlosser on the elimination of dichloro compounds.
Scheme 33: Stereoselective variation caused by change of solvent.
Scheme 34: Elimination of gem-dichloride 189 to afford alkene 190.
Scheme 35: Oxidation of enones to dichlorides and in situ elimination thereof.
Scheme 36: Oxidation of allylic alcohols to dichlorides and in situ elimination thereof.
Scheme 37: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 38: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 39: Fluorine–chlorine exchange followed by elimination.
Scheme 40: Intercepting cations with alkynes and trapping of the alkenyl cation intermediate with chloride.
Scheme 41: Investigations by Mayr and co-workers.
Scheme 42: In situ activation of benzyl alcohol 230 with BCl3.
Scheme 43: In situ activation of benzylic alcohols with TiCl4.
Scheme 44: In situ activation of benzylic alcohols with FeCl3.
Scheme 45: In situ activation of benzylic alcohols with FeCl3.
Scheme 46: In situ activation of aliphatic chlorides and alcohols with ZnCl2, InCl3, and FeCl3.
Scheme 47: In situ generation of benzylic cations and trapping thereof with alkynes.
Scheme 48: Intramolecular trapping reactions affording alkenyl halides.
Scheme 49: Intramolecular trapping reactions affording alkenyl chlorides.
Scheme 50: Intramolecular trapping reactions of oxonium and iminium ions affording alkenyl chlorides.
Scheme 51: Palladium and nickel-catalyzed coupling reactions to afford alkenyl chlorides.
Scheme 52: Rhodium-catalyzed couplings of 1,2-trans-dichloroethene with arylboronic esters.
Scheme 53: First report on monoselective coupling reactions for 1,1-dichloroalkenes.
Scheme 54: Negishi’s and Barluenga’s contributions.
Scheme 55: First mechanistic investigation by Johnson and co-workers.
Scheme 56: First successful cross-metathesis with choroalkene 260.
Scheme 57: Subsequent studies by Johnson.
Scheme 58: Hoveyda and Schrock’s work on stereoretentive cross-metathesis with molybdenum-based catalysts.
Scheme 59: Related work with (Z)-dichloroethene.
Scheme 60: Further ligand refinement and traceless protection of functional groups with HBpin.
Scheme 61: Alkenyl chloride synthesis by Wittig reaction.
Scheme 62: Alkenyl chloride synthesis by Julia olefination.
Scheme 63: Alkenyl chloride synthesis by reaction of ketones with Mg/TiCl4 mixture.
Scheme 64: Frequently used allylic substitution reactions which lead to alkenyl chlorides.
Scheme 65: Enantioselective allylic substitutions.
Scheme 66: Synthesis of alkenyl chlorides bearing an electron-withdrawing group.
Scheme 67: Synthesis of α-nitroalkenyl chlorides from aldehydes.
Scheme 68: Synthesis of alkenyl chlorides via elimination of an in situ generated geminal dihalide.
Scheme 69: Carbenoid approach reported by Pace.
Scheme 70: Carbenoid approach reported by Pace.
Scheme 71: Ring opening of cyclopropenes in the presence of MgCl2.
Scheme 72: Electrophilic chlorination of alkenyl MIDA boronates to Z- or E-alkenyl chlorides.
Scheme 73: Hydroalumination and hydroboration of alkynyl chlorides.
Scheme 74: Carbolithiation of chloroalkynes.
Scheme 75: Chlorination of enamine 420.
Scheme 76: Alkyne synthesis by elimination of alkenyl chlorides.
Scheme 77: Reductive lithiation of akenyl chlorides.
Scheme 78: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 79: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 80: Addition–elimination reaction of alkenyl chloride 9 with organolithium reagents.
Scheme 81: C–H insertions of lithiumcarbenoids.
Scheme 82: Pd-catalyzed coupling reactions with alkenyl chlorides as coupling partner.
Scheme 83: Ni-catalyzed coupling of alkenylcopper reagent with alkenyl chloride 183.
Scheme 84: Ni-catalyzed coupling of heterocycle 472 with alkenyl chloride 473.
Scheme 85: Synthesis of α-chloroketones by oxidation of alkenyl chlorides.
Scheme 86: Tetrahalogenoferrate(III)-promoted oxidation of alkenyl chlorides.
Scheme 87: Chlorine–deuterium exchange promoted by a palladium catalyst.
Scheme 88: Reaction of alkenyl chlorides with thiols in the presence of AIBN (azobisisobutyronitrile).
Scheme 89: Chloroalkene annulation.
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
- –halogen exchange in the ABC-fragment 38 followed by 1,2-addition to the ketone moiety in the F-ring fragment 42. Protection group manipulations allowed for the union of both fragments to advanced intermediate 43 in three steps in 42%, setting the stage for the key cyclization reactions in this sequence
- butenolide moiety, selective α-methylation, formation of a lactam, reduction of the former to an amine, and installation of two different protecting groups. Aryl bromide 53 (fragment B) was then ready for coupling. Lithium–halogen exchange in fragment B 53 and subsequent 1,2-addition to fragment A 47
- coupling was carried out via lithium–halogen exchange, 1,2-addition, and subsequent oxidation to give ketone 48. Photoinduced excited-state Nazarov cyclization installed the cyclopentenone C-ring with correct stereoconfiguration at C9 and C10 in excellent yield. Ketone reduction and global deprotection
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...
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
- ; and subsequent conversion of the ketone in 20 to the vinyl iodide in 21 – via hydrazone formation, lithium–halogen exchange, and final nucleophilic substitution – secured the Norrish–Yang cyclization precursor 22. Following systematic optimization of reaction conditions, irradiation of 22 with 100 W
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.
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
- monochlorination and bromination of ketone 6 via enamine 9a [31], and it was envisaged that 9a would be a suitable substrate to achieve the double halogenation using an excess of electrophilic halogen. When enamine 9a was treated with 1.0 mol equivalent of trichloroisocyanouric acid (TCCA), a reagent which can
- chiral halogenated lactones, which could be useful in the enantioselective synthesis of valuable drug precursors. The syntheses feature the use of readily available and cheap starting materials, and we have also demonstrated some of these transformations on a gram scale. Halogen-containing butyrolactone
Graphical Abstract
Figure 1: Halogen-containing butyrolactone-derived bioactives.
Scheme 1: Preparation of chlorinated and brominated lactones 8a,b and 11a,b.
Scheme 2: Preparation of fluorinated lactone 14.
Scheme 3: Fluorination of LGO (5) and conversion to lactone 17.
Scheme 4: Trifluoromethylation of 9a,b and 15 and subsequent Baeyer–Villiger oxidation.
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
- transferred to the radical. Important processes of this kind are hydrogen atom transfer (HAT) and halogen atom abstraction. An intramolecular group transfer reaction can result in the net migration of a functional group. Addition of a radical to a π-bond (carbon–carbon or carbon–heteroatom) is another common
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...
Research towards selective inhibition of the CLK3 kinase
- Vinay Kumar Singh,
- Frédéric Justaud,
- Dabbugoddu Brahmaiah,
- Nangunoori Sampath Kumar,
- Blandine Baratte,
- Thomas Robert,
- Stéphane Bach,
- Chada Raji Reddy,
- Nicolas Levoin and
- René L. Grée
Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172
- decided to prepare also the same molecules with hydrogen instead of the chlorine in meta position of the anilino group. Our previous work on DB18 suggested indeed that the chlorine atom is implicated in intramolecular halogen–π interaction, ending in a conformational constraint and ligand rigidity [24
Graphical Abstract
Figure 1: A) Sequence of amino acids in CLK3 as compared to the three other CLKs; B) Structure of CLK3 highli...
Figure 2: A) Docking of our previous inhibitor (DB18) in CLK3 and B) our working hypothesis.
Figure 3: Design of our target molecules.
Scheme 1: Synthesis of the intermediate anilino-2-quinazolines 7a and 7b.
Scheme 2: Synthesis of the targeted anilino-2-quinazolines 10 and 13.
Figure 4: Primary evaluation of the inhibition of the new quinazolines against a short panel of mammalian kin...
Figure 5: Docking of VS-77 in CLK3.
Figure 6: Docking of VS-77 in Hs_DYRK1A (PDB ID: 8T2H [26]).
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
- transformations of 121 generated bromodiene 122. Next, the metal–halogen exchange/intermolecular addition of 122 with aldehyde (+)-123 and in situ PtCl2-promoted hydrolysis and hydration gave tricyclic product 124. The BnMe3NOH-mediated intramolecular Michael/aldol cascade reaction of 124 constructed the C/D
Graphical Abstract
Figure 1: Several representative terpenoid and alkaloid natural products synthesized by applying desymmetric ...
Figure 2: Selected terpenoid and alkaloid natural products synthesized by applying desymmetric enantioselecti...
Scheme 1: The total synthesis of (+)-aplysiasecosterol A (6) by Li [14].
Scheme 2: The total synthesis of (−)-cyrneine A by Han [31].
Scheme 3: The total syntheses of three cyrneine diterpenoids by Han [31,32].
Scheme 4: The total synthesis of (−)-hamigeran B and (−)-4-bromohamigeran B by Han [51].
Scheme 5: The total synthesis of (+)-randainin D by Baudoin [53].
Scheme 6: The total synthesis of (−)-hunterine A and (−)-aspidospermidine by Stoltz [58].
Scheme 7: The total synthesis of (+)-toxicodenane A by Han [65,66].
Scheme 8: The formal total synthesis of (−)-conidiogeone B and total synthesis of (−)-conidiogeone F by Lee a...
Scheme 9: The total syntheses of four conidiogenones natural products by Lee and Han [72].
Scheme 10: The total synthesis of (−)-platensilin by Lou and Xu [82].
Scheme 11: The total synthesis of (−)-platencin and (−)-platensimycin by Lou and Xu [82].
Scheme 12: The total synthesis of (+)-isochamaecydin and (+)-chamaecydin by Han [86].
Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis
- Rasma Kroņkalne,
- Rūdolfs Beļaunieks,
- Armands Sebris,
- Anatoly Mishnev and
- Māris Turks
Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154
- have been induced by addition of external halogen or selenium electrophiles and Brønsted acids. This encouraged us to develop a methodology involving a copper-catalyzed terminal alkyne arylation of propargylsilanes by diaryl-λ3-iodanes, followed by 1,2-silyl shift and terminated by nucleophile addition
- using the symmetrical dithiophen-2-yliodonium p-tosylate (I-7). It should be noted that all products 8 were obtained with exclusive (E)-selectivity. Tetrahydrofuran 8a and some analogous compounds could be synthesized previously from alcohol 7d, but in two steps, employing a halogen electrophile-induced
Graphical Abstract
Scheme 1: Alkyne arylation with diaryl-λ3-iodanes in the context of 1,2-silyl shift and potential cyclization....
Scheme 2: Competing mechanistic pathways for diene 10 and indene 11 formation.
Scheme 3: Reaction scope for the synthesis of arylated tetrahydrofurans 8. Conditions: All reactions were per...
Scheme 4: Synthesis of lactone and pyrrolidine derivatives. Conditions: ac7e = 0.1 mmol/mL. bReaction conditi...
Scheme 5: Proposed arylation–heterocyclization mechanism for internal nucleophile-containing silanes 7.
Scheme 6: Arylation of C5-chain containing acylamides 16a–c. aThe reaction was performed under modified condi...
Photoswitches beyond azobenzene: a beginner’s guide
- Michela Marcon,
- Christoph Haag and
- Burkhard König
Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143
- (37) followed by reduction with Zn/Ba(OH)2 and partial re-oxidation (Scheme 12A) [52]. They can also be obtained from o-halogenated benzyl bromides 40 by lithium–halogen exchange followed by nucleophilic substitution and a second lithium–halogen exchange with iodine (Scheme 12B) or by nickel-catalysed
Graphical Abstract
Figure 1: Energy diagram of a two-state photoswitch. Figure 1 was redrawn from [2].
Figure 2: Example of the absorption spectra of the isomers of a photoswitch with most efficient irradiation w...
Scheme 1: Photoswitch classes described in this review.
Figure 3: Azoheteroarenes.
Scheme 2: E–Z Isomerisation (top) and mechanisms of thermal Z–E isomerisation (bottom).
Scheme 3: Rotation mechanism favoured by the electron displacement in push–pull systems. Selected examples of...
Figure 4: A) T-shaped and twisted Z-isomers determine the thermal stability and the Z–E-PSS (selected example...
Figure 5: Effect of di-ortho-substitution on thermal half-life and PSS.
Figure 6: Selected thermal lifetimes of azoindoles in different solvents and concentrations. aConcentration o...
Figure 7: Aryliminopyrazoles: N-pyrazoles (top) and N-phenyl (bottom).
Scheme 4: Synthesis of symmetrical heteroarenes through oxidation (A), reduction (B), and the Bayer–Mills rea...
Scheme 5: Synthesis of diazonium salt (A); different strategies of azo-coupling: with a nucleophilic ring (B)...
Scheme 6: Synthesis of arylazothiazoles 25 (A) and heteroaryltriazoles 28 (B).
Scheme 7: Synthesis of heteroarylimines 31a,b [36-38].
Figure 8: Push–pull non-ionic azo dye developed by Velasco and co-workers [45].
Scheme 8: Azopyridine reported by Herges and co-workers [46].
Scheme 9: Photoinduced phase transitioning azobispyrazoles [47].
Figure 9: Diazocines.
Scheme 10: Isomers, conformers and enantiomers of diazocine.
Scheme 11: Partial overlap of the ππ* band with electron-donating substituents and effect on the PSS. Scheme 11 was ada...
Figure 10: Main properties of diazocines with different bridges. aMeasured in n-hexane [56]. bMeasured in THF. cMe...
Scheme 12: Synthesis of symmetric diazocines.
Scheme 13: Synthesis of asymmetric diazocines.
Scheme 14: Synthesis of O- and S-heterodiazocines.
Scheme 15: Synthesis of N-heterodiazocines.
Scheme 16: Puromycin diazocine photoswitch [60].
Figure 11: Indigoids.
Figure 12: The main representatives of the indigoid photoswitch class.
Scheme 17: Deactivation process that prevents Z-isomerisation of indigo.
Figure 13: Stable Z-indigo derivative synthesised by Wyman and Zenhäusern [67].
Figure 14: Selected examples of indigos with aliphatic and aromatic substituents [68]. Dashed box: proposed π–π in...
Scheme 18: Resonance structures of indigo and thioindigo involving the phenyl ring.
Scheme 19: Possible deactivation mechanism for 4,4'-dihydroxythioindigo [76].
Scheme 20: Effect of different heteroaryl rings on the stability and the photophysical properties of hemiindig...
Figure 15: Thermal half-lives of red-shifted hemithioindigos in toluene [79]. aMeasured in toluene-d8.
Scheme 21: Structures of pyrrole [81] and imidazole hemithioindigo [64].
Figure 16: Examples of fully substituted double bond hemithioindigo (left), oxidised hemithioindigos (centre),...
Scheme 22: Structure of iminothioindoxyl 72 (top) and acylated phenyliminoindolinone photoswitch 73 (bottom). ...
Scheme 23: (top) Transition states of iminothioindoxyl 72. The planar transition state is associated with a lo...
Scheme 24: Baeyer–Drewsen synthesis of indigo (top) and N-functionalisation strategies (bottom).
Scheme 25: Synthesis of hemiindigo.
Scheme 26: Synthesis of hemithioindigo and iminothioindoxyl.
Scheme 27: Synthesis of double-bond-substituted hemithioindigos.
Scheme 28: Synthesis of phenyliminoindolinone.
Scheme 29: Hemithioindigo molecular motor [85].
Figure 17: Arylhydrazones.
Scheme 30: Switching of arylhydrazones. Note: The definitions of stator and rotor are arbitrary.
Scheme 31: Photo- and acidochromism of pyridine-based phenylhydrazones.
Scheme 32: A) E–Z thermal inversion of a thermally stable push–pull hydrazone [109]. B) Rotation mechanism favoured...
Scheme 33: Effect of planarisation on the half-life.
Scheme 34: The longest thermally stable hydrazone switches reported so far (left). Modulation of thermal half-...
Figure 18: Dependency of t1/2 on concentration and hypothesised aggregation-induced isomerisation.
Figure 19: Structure–property relationship of acylhydrazones.
Scheme 35: Synthesis of arylhydrazones.
Scheme 36: Synthesis of acylhydrazones.
Scheme 37: Photoswitchable fluorophore by Aprahamian et al. [115].
Scheme 38: The four-state photoswitch synthesised by the Cigáň group [116].
Figure 20: Diarylethenes.
Scheme 39: Isomerisation and oxidation pathway of E-stilbene to phenanthrene.
Scheme 40: Strategies adapted to avoid E–Z isomerisation and oxidation.
Scheme 41: Molecular orbitals and mechanism of electrocyclisation for a 6π system.
Figure 21: Aromatic stabilisation energy correlated with the thermal stability of the diarylethenes [127,129].
Figure 22: Half-lives of diarylethenes with increasing electron-withdrawing groups [128,129].
Scheme 42: Photochemical degradation pathway promoted by electron-donating groups [130].
Figure 23: The diarylethenes studied by Hanazawa et al. [134]. Increased rigidity leads to bathochromic shift.
Scheme 43: The dithienylethene synthesised by Nakatani's group [135].
Scheme 44: Synthesis of perfluoroalkylated diarylethenes.
Scheme 45: Synthesis of 139 and 142 via McMurry coupling.
Scheme 46: Synthesis of symmetrical derivatives 145 via Suzuki–Miyaura coupling.
Scheme 47: Synthesis of acyclic 148, malonic anhydride 149, and maleimide derivatives 154.
Figure 24: Gramicidin S (top left) and two of the modified diarylethene derivatives: first generation (bottom ...
Scheme 48: Pyridoxal 5'-phosphate and its reaction with an amino acid (top). The analogous dithienylethene der...
Figure 25: Fulgides.
Scheme 49: The three isomers of fulgides.
Scheme 50: Thermal and photochemical side products of unsubstituted fulgide [150].
Figure 26: Maximum absorption λc of the closed isomer compared with the nature of the aromatic ring and the su...
Scheme 51: Possible rearrangement of the excited state of 5-dimethylaminoindolylfulgide [153].
Figure 27: Quantum yields of ring closure (ΦE→C) and E–Z isomerisation (ΦE→Z) correlated with the increasing s...
Scheme 52: Active (Eα) and inactive (Eβ) conformers (left) and the bicyclic sterically blocked fulgide 169 (ri...
Scheme 53: Quantum yield of ring-opening (ΦC→E) and E–Z isomerisation (ΦE→Z) for different substitution patter...
Scheme 54: Stobbe condensation pathway for the synthesis of fulgides 179, fulgimides 181 and fulgenates 178.
Scheme 55: Alternative synthesis of fulgides through Pd-catalysed carbonylation.
Scheme 56: Optimised synthesis of fulgimides [166].
Scheme 57: Photoswitchable FRET with a fulgimide photoswitch [167].
Scheme 58: Three-state fulgimide strategy by Slanina's group.
Figure 28: Spiropyrans.
Scheme 59: Photochemical (left) and thermal (right) ring-opening mechanisms for an exemplary spiropyran with a...
Figure 29: Eight possible isomers of the open merocyanine according to the E/Z configurations of the bonds hig...
Scheme 60: pH-Controlled photoisomerisation between the closed spiropyran 191-SP and the open E-merocyanine 19...
Scheme 61: Behaviour of spiropyran in water buffer according to Andréasson and co-workers [180]. 192-SP in an aqueo...
Scheme 62: (left box) Proposed mechanism of basic hydrolysis of MC [184]. (right box) Introduction of electron-dona...
Scheme 63: Photochemical interconversion of naphthopyran 194 (top) and spirooxazine 195 (bottom) photoswitches...
Scheme 64: Synthesis of spiropyrans and spirooxazines 198 and the dicondensation by-product 199.
Scheme 65: Alternative synthesis of spiropyrans and spirooxazines with indolenylium salt 200.
Scheme 66: Synthesis of 4’-substituted spiropyrans 203 by condensation of an acylated methylene indoline 201 w...
Scheme 67: Synthesis of spironaphthopyrans 210 by acid-catalysed condensation of naphthols and diarylpropargyl...
Scheme 68: Photoswitchable surface wettability [194].
Figure 30: Some guiding principles for the choice of the most suitable photoswitch. Note that this guide is ve...
Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue
- Mai Uchibori,
- Nanami Murate,
- Kanako Shima,
- Tatsunori Sakagami,
- Ko Kanehisa,
- Gary James Richards,
- Akiko Hori and
- Osamu Kitagawa
Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138
- , Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan 10.3762/bjoc.21.138 Abstract In single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one and the thione analogue, a unique association based on a halogen–π interaction was detected. In racemic and optically pure
- N-(2-bromo- or 2-chlorophenyl)quinolin-2-ones, homochiral layered polymers, which consist of (P)- or (M)-atropisomers, were formed through intermolecular halogen–π association. The halogen–π association in the racemates is due to a halogen bond (C–X···π) between a σ-hole on the halogen atom and a π
- -electron on the quinolinone benzene ring, while that in optically pure forms is caused by an n–π* interaction between a lone electron pair on the halogen atom and a π* orbital of the quinolinone. In contrast to the formation of the homochiral layered polymer in quinolinones, in racemic N-(2-bromophenyl
Graphical Abstract
Figure 1: Various C–N atropisomeric compounds and their intermolecular interactions in single crystals.
Scheme 1: Synthesis of N-(2-halophenyl)quinolin-2-ones 1a,b and quinoline-2-thione 2a.
Figure 2: Intramolecular associations detected in crystals of rac-1a and rac-1b.
Figure 3: Intramolecular association detected in the crystals of (P)-1a and (P)-1b.
Figure 4: Angles (θ, α) and distances (d) in racemate rac-1a,b and (P)-1a,b.
Figure 5: Crystal structure of racemic quinoline-2-thione rac-2a.
Influence of the cation in hypophosphite-mediated catalyst-free reductive amination
- Natalia Lebedeva,
- Fedor Kliuev,
- Olesya Zvereva,
- Klim Biriukov,
- Evgeniya Podyacheva,
- Maria Godovikova,
- Oleg I. Afanasyev and
- Denis Chusov
Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130
- halogen atom transfer (XAT) agent [17][18]. Standard reduction potentials illustrate that hypophosphite is a powerful four-electron reductant [19]. Our previous studies have proved that NaH2PO2 can be a selective reducing agent in the catalyst-free reductive amination process [20][21][22] that can impart
Graphical Abstract
Scheme 1: Rationale of the current study: a) Our previous work [20]; b) this work.
Scheme 2: Comparison of KH2PO2 and NaH2PO2 under the optimal conditions.
Figure 1: Substrate scope. Reaction conditions: carbonyl compound (1.45 mmol, 1 equiv), amine (1.81 mmol, 1.2...
Scheme 3: Control experiments.
Scheme 4: Experiments with D3PO2.
Scheme 5: Principal steps of the mechanism of the reductive amination with K2CO3/H3PO2 reducing system.
Figure 2: Reaction profile and DFT energies of intermediates and transition states. M062X functional with the...
Photocatalysis and photochemistry in organic synthesis
- Timothy Noël and
- Bartholomäus Pieber
Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128
- ], hydrogen atom transfer [22], halogen atom transfer [23], and energy transfer catalysis [24][25] – have been established as powerful additions to the arsenal of photon-driven reactions. Three articles in this thematic issue exemplify this: The Molloy group developed an intramolecular [2 + 2]-cycloaddition
- of a dehydroalanine derivative using silane-mediated halogen atom transfer [28]. Dual catalytic approaches that merge photocatalysis with Lewis acid [29], organo- [30], or transition metal catalysis [31] have enabled access to bond formations that are otherwise challenging to achieve. In particular
Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds
- Lidia Zaharieva,
- Vera Deneva,
- Fadhil S. Kamounah,
- Nikolay Vassilev,
- Ivan Angelov,
- Michael Pittelkow and
- Liudmil Antonov
Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105
- to the low basicity of the proton-accepting nitrogen atom, the KE* form spontaneously goes to E*, which closes the channel to the twisting region. On the other side there is substantial number of papers describing the very long-lived cis isomers in ortho-halogen-substituted azobenzenes [38][85][86
Graphical Abstract
Scheme 1: Investigated compounds.
Scheme 2: Long-range PT in the studied compounds along with undesired processes of E/Z isomerization. The ind...
Figure 1: Simulated absorption spectra of the tautomers of 1 in toluene. The spectra in acetonitrile are show...
Figure 2: Normalized absorption spectra of 1.
Figure 3: Absorption spectra of 1 in acetonitrile with stepwise addition of water.
Figure 4: VT 1H NMR spectra of compound 1 in acetonitrile-d3.
Figure 5: Changes in the absorption spectrum of 2 in acetonitrile upon addition of trifluoroacetic acid (TFA)...
Figure 6: Ground (M06-2X/TZVP) and excited (CAM-B3LYP/TZVP) state potential energy surface of compound 1 in t...
Figure 7: Changes of the absorbance of compound 1 at 465 nm in toluene upon turning on and off the irradiatio...
Figure 8: a) Change of ΔE(K-E) in kcal/mol as a function of the substitution on different positions (2–6) in ...
Scheme 3: Perspective switching compounds, generated by the computational quantum chemistry calculations.
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
- to a potentially even larger library of amide isosteres. The scope of the carbon nucleophiles is very broad and includes alkyls, alkenyls, alkynyls, aryls and heteroaryls (e.g., pyridine, indole, thiophene), as well as (poly)substituted phenyls bearing a nitrile or halogen(s). On the other hand, the
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.
Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer
- Hao-Sen Wang,
- Lin Li,
- Xin Chen,
- Jian-Li Wu,
- Kai Sun,
- Xiao-Lan Chen,
- Ling-Bo Qu and
- Bing Yu
Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100
- C–C or C–heteroatom bonds. The incorporation of HAT strategies into the functionalization of C–H bonds represents a significant advancement in synthetic organic chemistry for their high atom economy and step economy. HAT reagents (HR), including alkoxyl, acyloxyl, halogen radicals, and amidyl
- require electrophilic heterocycles. These limitations hinder the broader application of such systems. Alexanian’s group modified amidyl radical precursors by incorporating halogen atoms, transforming them into bifunctional reagents. The HAT component of amidyl radical precursors was facilitated by amidyl
- radicals, while halogenation was promoted by the introduced halogen atom [26]. In 2014, Alexanian’s group reported a site-selective aliphatic C–H bromination utilizing modified HRP as both the bromination reagent and HAT reagent (Scheme 11) [25]. Initiated by visible light, HRP-10 underwent homolytic
Graphical Abstract
Figure 1: (a) BDE of C–H. (b) Direct functionalization of C–H catalyzed by transition-metal. (c) Direct funct...
Figure 2: (a) Amidyl radical-enabled hydrogen atom transfer. (b) Substituent effects to amidyl radical proper...
Figure 3: Representative photocatalysts discussed in this review.
Scheme 1: Alkylation of C(sp3)–H catalyzed by amidyl radical under visible light.
Scheme 2: Direct heteroarylation of C(sp3)–H catalyzed by amidyl radical under visible light.
Scheme 3: Alkylation of C(sp3)–H catalyzed by amidyl radical and metal-free photocatalyst under visible light....
Scheme 4: Alkylation of C(sp3)–H, Si–H, and Ge–H catalyzed by amidyl radical under visible light.
Scheme 5: Direct heteroarylation of C(sp3)–H catalyzed by synergistic promotion of amidyl radical and photoca...
Scheme 6: Direct B–H functionalization of icosahedral carboranes catalyzed by amidyl radical under visible li...
Scheme 7: Nucleophilic amination of C(sp3)–H enabled by amidyl radical under visible light.
Scheme 8: Direct heteroarylation of C(sp3)–H and C(sp3)–H without the presence of strong bases, acids, or oxi...
Scheme 9: Xanthylation of C(sp3)–H addressed by amidyl radical under visible light.
Scheme 10: Xanthylation of C(sp3)–H in polyolefins addressed by amidyl radical under visible light.
Scheme 11: Site-selective C(sp3)–H bromination implemented by amidyl radical under visible light.
Scheme 12: Site-selective chlorination of C(sp3)–H in natural products implemented by amidyl radical under vis...
Scheme 13: Alkylation of C(sp3)–H catalyzed by amidyl radical photocatalyst under visible light.
Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes
- Bartłomiej Pigulski
Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99
- azulene-embedded PAHs. This approach requires a halogen-functionalized precursor and typically employs a palladium catalyst. Dou and co-workers reported a last-stage intramolecular C–H arylation of substituted indenofluorenes 61 and 62 (Scheme 10) [57]. The palladium-catalysed reaction yielded fused
Graphical Abstract
Figure 1: a) Stone–Wales (red) and azulene (blue) defects in graphene; b) azulene and its selected resonance ...
Figure 2: Examples of azulene-embedded 2D allotropic forms of carbon: a) phagraphene and b) TPH-graphene.
Scheme 1: Synthesis of non-alternant isomers of pyrene (2 and 6) using dehydrogenation.
Scheme 2: Synthesis of non-alternant isomer 9 of benzo[a]pyrene and 14 of benzo[a]perylene using dehydrogenat...
Scheme 3: Synthesis of azulene-embedded isomers of benzo[a]pyrene (18 and 22) inspired by Ziegler–Hafner azul...
Figure 3: General strategies leading to azulene-embedded nanographenes: a) construction of azulene moiety in ...
Scheme 4: Synthesis of biradical PAHs possessing significant biradical character using oxidation of partially...
Scheme 5: Synthesis of dicyclohepta[ijkl,uvwx]rubicene (29) and its further modifications.
Scheme 6: Synthesis of warped PAHs with one embedded azulene subunit using Scholl-type oxidation.
Scheme 7: Synthesis of warped PAHs with two embedded azulene subunits using Scholl oxidation.
Scheme 8: Synthesis of azulene-embedded PAHs using [3 + 2] annulation accompanied by ring expansion.
Scheme 9: Synthesis of azulene-embedded isomers of linear acenes using [3 + 2] annulation accompanied by ring...
Scheme 10: Synthesis of azulene-embedded PAHs using intramolecular C–H arylation.
Scheme 11: Synthesis of azulene-embedded isomers of acenes using intramolecular C–H arylation.
Scheme 12: Synthesis of azulene-embedded PAHs using intramolecular condensations.
Scheme 13: Synthesis of azulene-embedded PAH 89 using palladium-catalysed [5 + 2] annulation.
Scheme 14: Synthesis of azulene-embedded PAHs using oxidation of substituents around the azulene core.
Scheme 15: Synthesis of azulene-embedded PAHs using the oxidation of reactive positions 1 and 3 of azulene sub...
Scheme 16: Synthesis of azulene-embedded PAHs using intramolecular C–H arylation.
Scheme 17: Synthesis of an azulene-embedded isomer of terylenebisimide using tandem Suzuki coupling and C–H ar...
Scheme 18: Synthesis of azulene embedded PAHs using a bismuth-catalyzed cyclization of alkenes.
Scheme 19: Synthesis of azulene-embedded nanographenes using intramolecular cyclization of alkynes.
Scheme 20: Synthesis of azulene-embedded graphene nanoribbons and azulene-embedded helicenes using annulation ...
Scheme 21: Synthesis of azulene-fused acenes.
Scheme 22: Synthesis of non-alternant isomer of perylene 172 using Yamamoto-type homocoupling.
Scheme 23: Synthesis of N- and BN-nanographenes with embedded azulene unit(s).
Scheme 24: On-surface synthesis of azulene-embedded nanographenes from benzenoid precursors via dehydrogenatio...
Scheme 25: On-surface synthesis of azulene-embedded nanographenes from benzenoid precursors.
Scheme 26: On-surface synthesis of azulene-embedded nanoribbons.
Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents
- Jiangfei Chen,
- Yi-Lin Qu,
- Ming Yuan,
- Xiang-Mei Wu,
- Heng-Pei Jiang,
- Ying Fu and
- Shengrong Guo
Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98
- groups on the aromatic ring (40a–d), effectively underwent this transformation. Halogen substituents (40e, 40f) on the substrates also demonstrated excellent reaction efficiency and substrate tolerance, further broadening the potential scope of applications. Regarding the reaction mechanism (Scheme 22
Graphical Abstract
Scheme 1: DTBP-mediated oxidative alkylarylation of activated alkenes.
Scheme 2: Iron-catalyzed oxidative 1,2-alkylarylation.
Scheme 3: Possible mechanism for the iron-catalyzed oxidative 1,2-alkylation of activated alkenes.
Scheme 4: A metal-free strategy for synthesizing 3,3-disubstituted oxindoles.
Scheme 5: Iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkenes.
Scheme 6: Proposed mechanism for the iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkene...
Scheme 7: Bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 8: Possible reaction mechanism for the bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 9: Radical cyclization of N-arylacrylamides with isocyanides.
Scheme 10: Plausible mechanism for the radical cyclization of N-arylacrylamides with isocyanides.
Scheme 11: Electrochemical dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 12: Plausible mechanism for the dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 13: Photocatalyzed cyclization of N-arylacrylamide and N,N-dimethylaniline.
Scheme 14: Proposed mechanism for the photocatalyzed cyclization of N-arylacrylamides and N,N-dimethylanilines....
Scheme 15: Electrochemical monofluoroalkylation cyclization of N-arylacrylamides with dimethyl 2-fluoromalonat...
Scheme 16: Proposed mechanism for the electrochemical radical cyclization of N-arylacrylamides with dimethyl 2...
Scheme 17: Photoelectrocatalytic carbocyclization of unactivated alkenes using simple malonates.
Scheme 18: Plausible mechanism for the photoelectrocatalytic carbocyclization of unactivated alkenes with simp...
Scheme 19: Bromide-catalyzed electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 20: Proposed mechanism for the electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 21: Visible light-mediated trifluoromethylarylation of N-arylacrylamides.
Scheme 22: Plausible reaction mechanism for the visible light-mediated trifluoromethylarylation of N-arylacryl...
Scheme 23: Electrochemical difluoroethylation cyclization of N-arylacrylamides with sodium difluoroethylsulfin...
Scheme 24: Electrochemical difluoroethylation cyclization of N-methyacryloyl-N-alkylbenzamides with sodium dif...
Scheme 25: Photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)su...
Scheme 26: Proposed mechanism for the photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamide...
Scheme 27: Visible-light-induced domino difluoroalkylation/cyclization of N-cyanamide alkenes.
Scheme 28: Proposed mechanism of photoredox-catalyzed radical domino difluoroalkylation/cyclization of N-cyana...
Scheme 29: Palladium-catalyzed oxidative difunctionalization of alkenes.
Scheme 30: Two possible mechanisms of palladium-catalyzed oxidative difunctionalization.
Scheme 31: Silver-catalyzed oxidative 1,2-alkyletherification of unactivated alkenes with α-bromoalkylcarbonyl...
Scheme 32: Photochemical radical cascade cyclization of dienes.
Scheme 33: Proposed mechanism for the photochemical radical cascade 6-endo cyclization of dienes with α-carbon...
Scheme 34: Photocatalyzed radical coupling/cyclization of N-arylacrylamides and.
Scheme 35: Photocatalyzed radical-type couplings/cyclization of N-arylacrylamides with sulfoxonium ylides.
Scheme 36: Possible mechanism of visible-light-induced radical-type couplings/cyclization of N-arylacrylamides...
Scheme 37: Visible-light-promoted difluoroalkylated oxindoles systhesis via EDA complexes.
Scheme 38: Possible mechanism for the visible-light-promoted radical cyclization of N-arylacrylamides with bro...
Scheme 39: A dicumyl peroxide-initiated radical cascade reaction of N-arylacrylamide with DCM.
Scheme 40: Possible mechanism of radical cyclization of N-arylacrylamides with DCM.
Scheme 41: An AIBN-mediated radical cascade reaction of N-arylacrylamides with perfluoroalkyl iodides.
Scheme 42: Possible mechanism for the reaction with perfluoroalkyl iodides.
Scheme 43: Photoinduced palladium-catalyzed radical annulation of N-arylacrylamides with alkyl halides.
Scheme 44: Radical alkylation/cyclization of N-Alkyl-N-methacryloylbenzamides with alkyl halides.
Scheme 45: Possible mechanism for the alkylation/cyclization with unactivated alkyl chlorides.
Scheme 46: Visible-light-driven palladium-catalyzed radical cascade cyclization of N-arylacrylamides with unac...
Scheme 47: NHC-catalyzed radical cascade cyclization of N-arylacrylamides with alkyl bromides.
Scheme 48: Possible mechanism of NHC-catalyzed radical cascade cyclization.
Scheme 49: Electrochemically mediated radical cyclization reaction of N-arylacrylamides with freon-type methan...
Scheme 50: Proposed mechanistic pathway of electrochemically induced radical cyclization reaction.
Scheme 51: Redox-neutral photoinduced radical cascade cylization of N-arylacrylamides with unactivated alkyl c...
Scheme 52: Proposed mechanistic hypothesis of redox-neutral radical cascade cyclization.
Scheme 53: Thiol-mediated photochemical radical cascade cylization of N-arylacrylamides with aryl halides.
Scheme 54: Proposed possible mechanism of thiol-mediated photochemical radical cascade cyclization.
Scheme 55: Visible-light-induced radical cascade bromocyclization of N-arylacrylamides with NBS.
Scheme 56: Possible mechanism of visible-light-induced radical cascade cyclization.
Scheme 57: Decarboxylation/radical C–H functionalization by visible-light photoredox catalysis.
Scheme 58: Plausible mechanism of visible-light photoredox-catalyzed radical cascade cyclization.
Scheme 59: Visible-light-promoted tandem radical cyclization of N-arylacrylamides with N-(acyloxy)phthalimides....
Scheme 60: Plausible mechanism for the tandem radical cyclization reaction.
Scheme 61: Visible-light-induced aerobic radical cascade alkylation/cyclization of N-arylacrylamides with alde...
Scheme 62: Plausible mechanism for the aerobic radical alkylarylation of electron-deficient amides.
Scheme 63: Oxidative decarbonylative [3 + 2]/[5 + 2] annulation of N-arylacrylamide with vinyl acids.
Scheme 64: Plausible mechanism for the decarboxylative (3 + 2)/(5 + 2) annulation between N-arylacrylamides an...
Scheme 65: Rhenium-catalyzed alkylarylation of alkenes with PhI(O2CR)2.
Scheme 66: Plausible mechanism for the rhenium-catalyzed decarboxylative annulation of N-arylacrylamides with ...
Scheme 67: Visible-light-induced one-pot tandem reaction of N-arylacrylamides.
Scheme 68: Plausible mechanism for the visible-light-initiated tandem synthesis of difluoromethylated oxindole...
Scheme 69: Copper-catalyzed redox-neutral cyanoalkylarylation of activated alkenes with cyclobutanone oxime es...
Scheme 70: Plausible mechanism for the copper-catalyzed cyanoalkylarylation of activated alkenes.
Scheme 71: Photoinduced alkyl/aryl radical cascade for the synthesis of quaternary CF3-attached oxindoles.
Scheme 72: Plausible photoinduced electron-transfer (PET) mechanism.
Scheme 73: Photoinduced cerium-mediated decarboxylative alkylation cascade cyclization.
Scheme 74: Plausible reaction mechanism for the decarboxylative radical-cascade alkylation/cyclization.
Scheme 75: Metal-free oxidative tandem coupling of activated alkenes.
Scheme 76: Control experiments and possible mechanism for 1,2-carbonylarylation of alkenes with carbonyl C(sp2...
Scheme 77: Silver-catalyzed acyl-arylation of activated alkenes with α-oxocarboxylic acids.
Scheme 78: Proposed mechanism for the decarboxylative acylarylation of acrylamides.
Scheme 79: Visible-light-mediated tandem acylarylation of olefines with carboxylic acids.
Scheme 80: Proposed mechanism for the radical cascade cyclization with acyl radical via visible-light photored...
Scheme 81: Erythrosine B-catalyzed visible-light photoredox arylation-cyclization of N-arylacrylamides with ar...
Scheme 82: Electrochemical cobalt-catalyzed radical cyclization of N-arylacrylamides with arylhydrazines or po...
Scheme 83: Proposed mechanism of radical cascade cyclization via electrochemical cobalt catalysis.
Scheme 84: Copper-catalyzed oxidative tandem carbamoylation/cyclization of N-arylacrylamides with hydrazinecar...
Scheme 85: Proposed reaction mechanism for the radical cascade cyclization by copper catalysis.
Scheme 86: Visible-light-driven radical cascade cyclization reaction of N-arylacrylamides with α-keto acids.
Scheme 87: Proposed mechanism of visible-light-driven cascade cyclization reaction.
Scheme 88: Peroxide-induced radical carbonylation of N-(2-methylallyl)benzamides with methyl formate.
Scheme 89: Proposed cyclization mechanism of peroxide-induced radical carbonylation with N-(2-methylallyl)benz...
Scheme 90: Persulfate promoted carbamoylation of N-arylacrylamides and N-arylcinnamamides.
Scheme 91: Proposed mechanism for the persulfate promoted radical cascade cyclization reaction of N-arylacryla...
Scheme 92: Photocatalyzed carboacylation with N-arylpropiolamides/N-alkyl acrylamides.
Scheme 93: Plausible mechanism for the photoinduced carboacylation of N-arylpropiolamides/N-alkyl acrylamides.
Scheme 94: Electrochemical Fe-catalyzed radical cyclization with N-arylacrylamides.
Scheme 95: Plausible mechanism for the electrochemical Fe-catalysed radical cyclization of N-phenylacrylamide.
Scheme 96: Substrate scope of the selective functionalization of various α-ketoalkylsilyl peroxides with metha...
Scheme 97: Proposed reaction mechanism for the Fe-catalyzed reaction of alkylsilyl peroxides with methacrylami...
Scheme 98: EDA-complex mediated C(sp2)–C(sp3) cross-coupling of TTs and N-methyl-N-phenylmethacrylamides.
Scheme 99: Proposed mechanism for the synthesis of oxindoles via EDA complex.
Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates
- Alexander S. Budnikov,
- Igor B. Krylov,
- Fedor K. Monin,
- Valentina M. Merkulova,
- Alexey I. Ilovaisky,
- Liu Yan,
- Bing Yu and
- Alexander O. Terent’ev
Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96
- substitution pattern in the aryl ring does not have a significant effect on the yield of 3 for both acceptor and donor derivatives, which shows the versatility of the developed protocol. However, among halogen-containing derivatives, higher yields were observed for bromine-substituted ones (products 3i and 3l
Graphical Abstract
Scheme 1: Recent approaches for the synthesis of β-ketophosphonates by the oxyphosphorylation of unsaturated ...
Scheme 2: The scope of the discovered copper(II)-mediated phosphorylation of enol acetates.
Scheme 3: Gram-scale synthesis of 3a.
Scheme 4: Control experiments.
Scheme 5: Proposed mechanism for copper(II) mediated phosphorylation of enol acetates.
A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones
- Ashutosh Nath,
- John Mark Awad and
- Wei Zhang
Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92
- for all substitutes of 6a, 6h, 6r and 6j, which, are not ideal effective for IMDA cycloadditions compared to the other substitute cycloadditions. The R2 substituent on the imidazopyridine moiety in 6 was found to have a significant electronic impact on the IMDA cycloaddition. When R2 is a halogen (Br
Graphical Abstract
Figure 1: Bioactive compounds bearing imidazopyridine (red) and isoquinolinone-kind (blue) rings.
Scheme 1: GBB-initiated synthesis of imidazopyridine-fused isoquinolinones.
Scheme 2: GBB reaction and N-acylation for the preparation of imidazo[1,2-a]pyridines 6.
Scheme 3: Substrate scope for IMDA and dehydrative aromatization in making 8. Reaction conditions: 6 and AlCl3...
Figure 2: Transition state analysis of IMDA reactions for 6a, 6j, 6h and 6r.
Figure 3: Relative energy diagram for the synthesis of 8a from 6a.
Scheme 4: Using thiophene-2-carbaldehyde for the synthesis of 8t.
Scheme 5: Proposed mechanisms for IMDA reaction and dehydration re-aromatization.
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
- preparing the organometallic reagent using halogen-metal exchange, which proved feasible for small scale operations. Alcohol 126 was converted into its iodide derivative 127 in 93% yield using Ph3P/I2/imidazole reagent. Halogen-metal exchange of 127 with tert-butyllithium proceeded efficiently, and
- , reductive work up, iodination, halogen-metal exchange, and transmetallation for compound (–)-128, followed by reaction with (S)-120, provided the deoxypropionate product (+)-131 in 78% yield over three steps, with dr >95:5. Finally, another ozonolysis followed by reductive work up with triphenylphospine
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.
Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold
- Henry S. T. Smith,
- Ben Giuliani,
- Kanchana Wijesekera,
- Kah Yean Lum,
- Sandra Duffy,
- Aaron Lock,
- Jonathan M. White,
- Vicky M. Avery and
- Rohan A. Davis
Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90
- -position (tele-substituted; Figure 1), distant from the halogen leaving group at position 5 [10]. A plausible reaction mechanism was proposed by Korsik et al. [10]. The antimalarial activity of series 4 triazolopyrazine scaffolds is generally reduced by substitution of an amine functionality at the 8
- triazolopyrazines from 5-halogen substituted triazolopyrazines and primary amines now in hand, 13 other commercially available liquid primary amines were employed for the synthesis of additional aminated triazolopyrazine analogues (Scheme 2). TLC analysis of the room temperature reaction with phenethylamine (as
- C20H2635ClN6NaO2, 439.1620; found, 439.1616. (A) Position numbering on the pyrazine ring of 1,2,4-triazolo[4,3-a]pyrazine. (B) Illustration of ipso- and tele-substitution products for reactions of nucleophiles with 5-halogenated 1,2,4-triazolo[4,3-a]pyrazine, where X = halogen and Nuc = nucleophile. Key COSY
Graphical Abstract
Figure 1: (A) Position numbering on the pyrazine ring of 1,2,4-triazolo[4,3-a]pyrazine. (B) Illustration of i...
Scheme 1: Treatment of 1 with phenethylamine (PEA) under two different reaction conditions, (i) or (ii), gave ...
Figure 2: Key COSY (–), HMBC (→) and ROESY (↔) correlations for compound 2.
Figure 3: Thermal ellipsoid plot of compound 2.
Scheme 2: Chemical structures, reagents and conditions used to synthesise the new aminated triazolopyrazines 2...
Figure 4: Thermal ellipsoid plots for compounds 7 (A), 10 (B) and 15 (C).
