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Search for "glycol" in Full Text gives 267 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
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
- . The synthesis commenced with the treatment of precursor 92, obtained in three steps from ethylene glycol, with MeMgBr and catalytic 94/CuBr, yielding the 1,4-addition product 93 in 96% yield and excellent regioselectivity (ee 98%) (Scheme 15). The authors highlighted the scalability of this reaction
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 advances in synthetic approaches for bioactive cinnamic acid derivatives
- Betty A. Kustiana,
- Galuh Widiyarti and
- Teni Ernawati
Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85
- scaled up to a gram scale. Uozumi and co-workers (2019) reported a carbonylation under aqueous flow conditions using alkenyl halide 240 to prepare cinnamic acid (7) catalyzed by an amphiphilic polystyrene-poly(ethylene glycol) resin-supported Pd-diphenylphosphine catalyst (cat 6) (Scheme 65A) [31]. Also
Graphical Abstract
Figure 1: Biologically active cinnamic acid derivatives.
Scheme 1: General synthetic strategies for cinnamic acid derivatizations.
Scheme 2: Cinnamic acid coupling via isobutyl anhydride formation.
Scheme 3: Amidation reaction via O/N-pivaloyl activation.
Scheme 4: Cinnamic acid amidation using TCCA/PPh3 reagent.
Scheme 5: Cinnamic acid amidation using triazine-based reagents.
Scheme 6: Cinnamic acid amidation using continuous flow mechanochemistry.
Scheme 7: Cinnamic acid amidation using COMU as coupling reagent.
Scheme 8: Cinnamic acid amidation using allenone coupling reagent.
Scheme 9: Cinnamic acid amidation using 4-acetamidophenyl triflimide as reagent.
Scheme 10: Cinnamic acid amidation using methyltrimethoxysilane (MTM).
Scheme 11: Cinnamic acid amidation utilizing amine–borane reagent.
Scheme 12: Cinnamic acid amidation using TCCA/PPh3 reagent.
Scheme 13: Cinnamic acid amidation using PPh3/I2 reagent.
Scheme 14: Cinnamic acid amidation using PCl3 reagent.
Scheme 15: Cinnamic acid amidation utilizing pentafluoropyridine (PFP) as reagent.
Scheme 16: Cinnamic acid amidation using hypervalent iodine(III).
Scheme 17: Mechanochemical amidation using 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (TFEDMA) reagent.
Scheme 18: Methyl ester preparation using tris(2,4,6-trimethoxyphenyl)phosphine (TMPP).
Scheme 19: N-Trifluoromethyl amide preparation using isothiocyanate and AgF.
Scheme 20: POCl3-mediated amide coupling of carboxylic acid and DMF.
Scheme 21: O-Alkylation of cinnamic acid using alkylating agents.
Scheme 22: Glycoside preparation via Mitsunobu reaction.
Scheme 23: O/N-Acylation via rearrangement reactions.
Scheme 24: Amidation reactions using sulfur-based alkylating agents.
Scheme 25: Amidation reaction catalyzed by Pd0 via C–N cleavage.
Scheme 26: Amidation reaction catalyzed by CuCl/PPh3.
Scheme 27: Cu(II) triflate-catalyzed N-difluoroethylimide synthesis.
Scheme 28: Cu/Selectfluor-catalyzed transamidation reaction.
Scheme 29: CuO–CaCO3-catalyzed amidation reaction.
Scheme 30: Ni-catalyzed reductive amidation.
Scheme 31: Lewis acidic transition-metal-catalyzed O/N-acylations.
Scheme 32: Visible-light-promoted amidation of cinnamic acid.
Scheme 33: Sunlight/LED-promoted amidation of cinnamic acid.
Scheme 34: Organophotocatalyst-promoted N–O cleavage of Weinreb amides to synthesize primary amides.
Scheme 35: Cinnamamide synthesis through [Ir] photocatalyst-promoted C–N-bond cleavage of tertiary amines.
Scheme 36: Blue LED-promoted FeCl3-catalyzed reductive transamidation.
Scheme 37: FPyr/TCT-catalyzed amidation of cinnamic acid derivative 121.
Scheme 38: Cs2CO3/DMAP-mediated esterification.
Scheme 39: HBTM organocatalyzed atroposelective N-acylation.
Scheme 40: BH3-catalyzed N-acylation reactions.
Scheme 41: Borane-catalyzed N-acylation reactions.
Scheme 42: Catalytic N-acylation reactions via H/F bonding activation.
Scheme 43: Brønsted base-catalyzed synthesis of cinnamic acid esters.
Scheme 44: DABCO/Fe3O4-catalyzed N-methyl amidation of cinnamic acid 122.
Scheme 45: Catalytic oxidation reactions of acylating agents.
Scheme 46: Preparation of cinnamamide-substituted benzocyclooctene using I(I)/I(III) catalysis.
Scheme 47: Pd-colloids-catalyzed oxidative esterification of cinnamyl alcohol.
Scheme 48: Graphene-supported Pd/Au alloy-catalyzed oxidative esterification via hemiacetal intermediate.
Scheme 49: Au-supported on A) carbon nanotubes (CNT) and B) on porous boron nitride (pBN) as catalyst for the ...
Scheme 50: Cr-based catalyzed oxidative esterification of cinnamyl alcohols with H2O2 as the oxidant.
Scheme 51: Co-based catalysts used for oxidative esterification of cinnamyl alcohol.
Scheme 52: Iron (A) and copper (B)-catalyzed oxidative esterification of cinnamaldehyde.
Scheme 53: NiHPMA-catalyzed oxidative esterification of cinnamaldehyde.
Scheme 54: Synthesis of cinammic acid esters through NHC-catalyzed oxidative esterification via intermolecular...
Scheme 55: Redox-active NHC-catalyzed esterification via intramolecular oxidation.
Scheme 56: Electrochemical conversion of cinnamaldehyde to methyl cinnamate.
Scheme 57: Bu4NI/TBHP-catalyzed synthesis of bisamides from cinnamalaldehyde N-tosylhydrazone.
Scheme 58: Zn/NC-950-catalyzed oxidative esterification of ketone 182.
Scheme 59: Ru-catalyzed oxidative carboxylation of terminal alkenes.
Scheme 60: Direct carboxylation of alkenes using CO2.
Scheme 61: Carboxylation of alkenylboronic acid/ester.
Scheme 62: Carboxylation of gem-difluoroalkenes with CO2.
Scheme 63: Photoredox-catalyzed carboxylation of difluoroalkenes.
Scheme 64: Ru-catalyzed carboxylation of alkenyl halide.
Scheme 65: Carboxylation of alkenyl halides under flow conditions.
Scheme 66: Cinnamic acid ester syntheses through carboxylation of alkenyl sulfides/sulfones.
Scheme 67: Cinnamic acid derivatives synthesis through a Ag-catalyzed decarboxylative cross-coupling proceedin...
Scheme 68: Pd-catalyzed alkyne hydrocarbonylation.
Scheme 69: Fe-catalyzed alkyne hydrocarbonylation.
Scheme 70: Alkyne hydrocarboxylation using CO2.
Scheme 71: Alkyne hydrocarboxylation using HCO2H as CO surrogate.
Scheme 72: Co/AlMe3-catalyzed alkyne hydrocarboxylation using DMF.
Scheme 73: Au-catalyzed oxidation of Au–allenylidenes.
Scheme 74: Pd-catalyzed C–C-bond activation of cyclopropenones to synthesize unsaturated esters and amides.
Scheme 75: Ag-catalyzed C–C-bond activation of diphenylcyclopropenone.
Scheme 76: Cu-catalyzed C–C bond activation of diphenylcyclopropenone.
Scheme 77: PPh3-catalyzed C–C-bond activation of diphenylcyclopropenone.
Scheme 78: Catalyst-free C–C-bond activation of diphenylcyclopropenone.
Scheme 79: Cu-catalyzed dioxolane cleavage.
Scheme 80: Multicomponent coupling reactions.
Scheme 81: Pd-catalyzed partial hydrogenation of electrophilic alkynes.
Scheme 82: Nickel and cobalt as earth-abundant transition metals used as catalysts for the partial hydrogenati...
Scheme 83: Metal-free-catalyzed partial hydrogenation of conjugated alkynes.
Scheme 84: Horner–Wadsworth–Emmons reaction between triethyl 2-fluoro-2-phosphonoacetate and aldehydes with ei...
Scheme 85: Preparation of E/Z-cinnamates using thiouronium ylides.
Scheme 86: Transition-metal-catalyzed ylide reactions.
Scheme 87: Redox-driven ylide reactions.
Scheme 88: Noble transition-metal-catalyzed olefination via carbenoid species.
Scheme 89: TrBF4-catalyzed olefination via carbene species.
Scheme 90: Grubbs catalyst (cat 7)/photocatalyst-mediated metathesis reactions.
Scheme 91: Elemental I2-catalyzed carbonyl-olefin metathesis.
Scheme 92: Cu-photocatalyzed E-to-Z isomerization of cinnamic acid derivatives.
Scheme 93: Ni-catalyzed E-to-Z isomerization.
Scheme 94: Dehydration of β-hydroxy esters via an E1cB mechanism to access (E)-cinnamic acid esters.
Scheme 95: Domino ring-opening reaction induced by a base.
Scheme 96: Dehydroamination of α-aminoester derivatives.
Scheme 97: Accessing methyl cinnamate (44) via metal-free deamination or decarboxylation.
Scheme 98: The core–shell magnetic nanosupport-catalyzed condensation reaction.
Scheme 99: Accessing cinnamic acid derivatives from acetic acid esters/amides through α-olefination.
Scheme 100: Accessing cinnamic acid derivatives via acceptorless α,β-dehydrogenation.
Scheme 101: Cu-catalyzed formal [3 + 2] cycloaddition.
Scheme 102: Pd-catalyzed C–C bond formation via 1,4-Pd-shift.
Scheme 103: NHC-catalyzed Rauhut–Currier reactions.
Scheme 104: Heck-type reaction for Cα arylation.
Scheme 105: Cu-catalyzed trifluoromethylation of cinnamamide.
Scheme 106: Ru-catalyzed alkenylation of arenes using directing groups.
Scheme 107: Earth-abundant transition-metal-catalyzed hydroarylation of α,β-alkynyl ester 374.
Scheme 108: Precious transition-metal-catalyzed β-arylation of cinnamic acid amide/ester.
Scheme 109: Pd-catalyzed β-amination of cinnamamide.
Scheme 110: S8-mediated β-amination of methyl cinnamate (44).
Scheme 111: Pd-catalyzed cross-coupling reaction of alkynyl esters with phenylsilanes.
Scheme 112: Pd-catalyzed β-cyanation of alkynyl amide/ester.
Scheme 113: Au-catalyzed β-amination of alkynyl ester 374.
Scheme 114: Metal-free-catalyzed Cβ-functionalizations of alkynyl esters.
Scheme 115: Heck-type reactions.
Scheme 116: Mizoroki–Heck coupling reactions using unconventional functionalized arenes.
Scheme 117: Functional group-directed Mizoroki–Heck coupling reactions.
Scheme 118: Pd nanoparticles-catalyzed Mizoroki–Heck coupling reactions.
Scheme 119: Catellani-type reactions to access methyl cinnamate with multifunctionalized arene.
Scheme 120: Multicomponent coupling reactions.
Scheme 121: Single atom Pt-catalyzed Heck coupling reaction.
Scheme 122: Earth-abundant transition metal-catalyzed Heck coupling reactions.
Scheme 123: Polymer-coated earth-abundant transition metals-catalyzed Heck coupling reactions.
Scheme 124: Earth-abundant transition-metal-based nanoparticles as catalysts for Heck coupling reactions.
Scheme 125: CN- and Si-based directing groups to access o-selective cinnamic acid derivatives.
Scheme 126: Amide-based directing group to access o-selective cinnamic acid derivatives.
Scheme 127: Carbonyl-based directing group to access o-selective cinnamic acid derivatives.
Scheme 128: Stereoselective preparation of atropisomers via o-selective C(sp2)–H functionalization.
Scheme 129: meta-Selective C(sp2)–H functionalization using directing group-tethered arenes.
Scheme 130: para-Selective C(sp2)–H functionalization using directing group-tethered arenes.
Scheme 131: Non-directed C(sp2)–H functionalization via electrooxidative Fujiwara–Moritani reaction.
Scheme 132: Interconversion of functional groups attached to cinnamic acid.
Scheme 133: meta-Selective C(sp2)–H functionalization of cinnamate ester.
Scheme 134: C(sp2)–F arylation using Grignard reagents.
Scheme 135: Truce–Smiles rearrangement of N-aryl metacrylamides.
Scheme 136: Phosphine-catalyzed cyclization of γ-vinyl allenoate with enamino esters.
Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions
- Wen-Hui Mi,
- Teng-Yu Huang,
- Xu-Dong Wang,
- Yu-Fei Ao,
- Qi-Qiang Wang and
- De-Xian Wang
Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72
- , while the glycol chains are oriented along the long axis in the opposite orientations. In packing mode, the submacrocycle units form close contacts through intermolecular hydrogen bonding, C–H···π, and lone pair–π interactions, resulting in a 1D linear assembly. Anion recognition With the functional
- carboxylate heads and the submacrocycles. Additionally, the protons Hd and He on the glycol chain showed initial downfield shifts followed by upfield shifts. These discontinuous chemical shift movements suggest the host–dicarboxylate interactions and the simultaneous conformational changes in the host upon
- hydroxy groups and engaging in anion–π interactions (2.70–2.92 Å) with the triazine rings (Figure 3). Additionally, the glycol arms of the macrocycle may further stabilize the anion binding through van der Waals interactions with the alkyl chains of the dianions. Driven by these multiple noncovalent
Graphical Abstract
Scheme 1: Synthesis of ultracycles.
Figure 1: (a, b) Crystal structure of B4aH (hydrogen atoms are omitted for clarity), and (c) the stacking str...
Figure 2: (a) The structures of host and guests, (b) 1H NMR spectra (298 K, 400 MHz, CD3CN) of B4aH upon titr...
Figure 3: (a–c) DFT-optimized structure of the B4aH-C72− complex. The blue dotted lines represent hydrogen bo...
Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra
- Yuuki Ishii,
- Minoru Yamaji,
- Fumito Tani,
- Kenta Goto,
- Yoshihiro Kubozono and
- Hideki Okamoto
Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53
- state. The orange and blue sites, respectively, indicate negative and positive regions (−0.02 ≈ 0.02 hartree). Synthesis of building blocks 10, 13, and 15. Reagents and conditions: a) NaBH4, MeOH, THF, reflux; b) PBr3, reflux; c) N-methylmorpholine-N-oxide, THF, reflux; d) ethylene glycol, p-TsOH
Graphical Abstract
Figure 1: Chemical structures of phenacenes studied in this work.
Scheme 1: Synthesis of building blocks 10, 13, and 15. Reagents and conditions: a) NaBH4, MeOH, THF, reflux; ...
Scheme 2: Synthesis of F8PIC, F8FUL, and F87PHEN. Reagents and conditions: a) KOH, 18-crown-6, CH2Cl2, reflux...
Figure 2: UV–vis and fluorescence spectra of F8PIC (a), F8FUL (b), and F87PHEN (c) (red lines) and the corres...
Figure 3: Photoluminescence spectra of F8PIC (a), F8FUL (b), and F87PHEN (c) in toluene at 77 K.
Figure 4: Electronic spectra of F8PIC (a), F8FUL (b), and F87PHEN (c) (red lines) and the corresponding paren...
Figure 5: (a) The MO diagrams of the parent and fluorinated phenacenes (B3LYP/6-31+G(d,p)). H and L, respecti...
Photocatalyzed elaboration of antibody-based bioconjugates
- Marine Le Stum,
- Eugénie Romero and
- Gary A. Molander
Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49
- facilitated a site-specific covalent linkage to the antibody, resulting in the formation of a DAR 2 ADC precursor. For their ADC design strategy, the group selected a polyethylene glycol (PEG) linker, as it enhances the water solubility of the ADC, while the payload consists of the cytotoxic agent DM1, which
Graphical Abstract
Figure 1: Representation of an antibody–drug conjugate. The antibody shown in this figure is from https://www...
Figure 2: a. Photoredox catalytic cycles; b. absorption spectrum of photosensitizers. Therapeutic window indi...
Figure 3: Graph representing the average number of publications focusing on photoredox chemistry applied to p...
Figure 4: Schematic procedure developed by Sato et al. on histidine photoinduced modification. The antibody s...
Figure 5: Schematic procedure of the divergent method developed by Sato et al. on histidine/tyrosine photoind...
Figure 6: Schematic procedure developed by Bräse et al. on photoinduced disulfide rebridging method.
Figure 7: Schematic procedure developed by Lang et al. on a photoinduced dual nickel photoredox-catalyzed app...
Figure 8: Schematic of the procedure developed by Chang et al. on photoinduced high affinity IgG Fc-binding s...
Figure 9: Potential advantages of photoredox chemistry for bioconjugation applied to antibodies. The antibody...
Figure 10: Representation of the photoinduced control of the DAR. The antibody shown in this figure is from ht...
Figure 11: Representation of a photoinduced control of multi-payloads ADC strategy. The antibody shown in this...
Cryptophycin unit B analogues
- Thomas Schachtsiek,
- Jona Voss,
- Maren Hamsen,
- Beate Neumann,
- Hans-Georg Stammler and
- Norbert Sewald
Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40
- approximately only one order of magnitude (IC50 = 0.52 nM) when tested on CCRF-CEM T lymphoblasts [20]. Loss of the meta-chloro substituent shows a similar trend. Functionalisation of the hydroxy group with ethylene glycol residues further decreases cytotoxicity, whereby this effect increases with increasing
Graphical Abstract
Figure 1: A: Structure of cryptophycin-52. B: Cryptophycin-52 derivatives modified with conjugation handles i...
Scheme 1: Synthesis of modified unit B derivatives. a) HNO3, H2SO4, 0 °C, 5 h, 48% (isolated as monohydrate);...
Figure 2: Molecular structure of Boc-ᴅ-Phe(4-NHMe)-OMe 7 as determined by single-crystal X-ray diffraction me...
Scheme 2: Synthesis of cryptophycin diols 24 and 25. a) EDC·HCl, DMAP, NEt3, CH2Cl2, 0 °C to rt, 22 h, 60%; b...
Scheme 3: Three-step diol–epoxide transformation starting from diols 24 and 25. a) (MeO)3CH, pyridinium p-tol...
Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC
- Bingnan Wang,
- Yong Lu and
- Chuo Chen
Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28
- polyethylene glycol (PEG) linker of various lengths is typically used to build a small library to identify a lead compound. For example, iVeliparib-AP6 (Figure 1) developed through this practice is a PROTAC that degrades poly(ADP-ribose) polymerase 2 (PARP2) selectively [5]. Results and Discussion The
Graphical Abstract
Figure 1: The structures of veliparib and iVeliparib-AP6.
Scheme 1: The synthetic route for iVeliparib-AP6.
Figure 2: Identification of the cryptic impurity of iVeliparib. The UV trace of the initially purified iVelip...
Figure 3: The structures of 6 and 7 and the MS ion extraction traces of 3, 4, 6, and 7 from HPLC analysis of ...
Scheme 2: The conversion of byproduct 6 to 10 to facilitate its removal.
Figure 4: The LUMO and electrostatic charges of thalidomide and its derivatives by DFT calculation at the ωB9...
Red light excitation: illuminating photocatalysis in a new spectrum
- Lucas Fortier,
- Corentin Lefebvre and
- Norbert Hoffmann
Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22
Graphical Abstract
Figure 1: Influence of the metal center M (Fe, Ru, Os) on the position of the MLCT and MC (metal-centered) ab...
Scheme 1: Red-light-mediated ring-closing metathesis through activation of a ruthenium catalyst by an osmium ...
Scheme 2: Photocatalyzed polymerization of dicylopentadiene mediated with red or blue light.
Figure 2: Comparison between [Ru(bpy)3]2+ and [Os(tpy)2]2+ in a photocatalyzed trifluoromethylation reaction:...
Scheme 3: Red-light photocatalyzed C–N cross-coupling reaction by T. Rovis et al. (SET = single-electron tran...
Figure 3: Red-light-mediated aryl oxidative addition with a bismuthinidene complex.
Scheme 4: Red-light-mediated reduction of aryl derivatives by O. S. Wenger et al. (PC = photocatalyst, anh = ...
Scheme 5: Red-light-mediated aryl halides reduction with an isoelectronic chromium complex (TDAE = tetrakis(d...
Scheme 6: Red-light-photocatalyzed trifluoromethylation of styrene derivatives with Umemoto’s reagent and a p...
Scheme 7: Red-light-mediated energy transfer for the cross-dehydrogenative coupling of N-phenyltetrahydroisoq...
Scheme 8: Red-light-mediated oxidative cyanation of tertiary amines with a phthalocyanin zinc complex.
Scheme 9: Formation of dialins and tetralins via a red-light-photocatalyzed reductive decarboxylation mediate...
Scheme 10: Oxidation of β-citronellol (28) via energy transfer mediated by a red-light activable silicon phtha...
Scheme 11: Formation of alcohol derivatives 32 from boron compounds 31 using chlorophyll (chl) as a red-light-...
Scheme 12: Red-light-driven reductive dehalogenation of α-halo ketones mediated by a thiaporphyrin photocataly...
Figure 4: Photoinduced electron transfer-reversible addition-fragmentation chain transfer polymerization medi...
Figure 5: Recent examples of red-light-mediated photocatalytic reactions with traditional organic dyes.
Figure 6: Squaraine photocatalysts used by Goddard et al. and aza-Henry reaction with squaraine-based photoca...
Figure 7: Reactions described by Goddard et al. involving 40 as the photocatalyst.
Figure 8: Various structures of squaraine derivatives used to initiate photopolymerizations.
Figure 9: Naturally occurring cyanins.
Figure 10: Influence of the structure on the photophysical properties of a cyanin dye.
Figure 11: NIR-light-mediated aza-Henry reaction photocatalyzed by 46.
Scheme 13: Photocatalyzed arylboronic acids oxidation by 46.
Figure 12: Cyanin structures synthetized and characterized by Goddard et al. (redox potentials given against s...
Figure 13: N,N′-Di-n-propyl-1,13-dimethoxyquinacridinium (55) with its redox potentials at its ground state an...
Scheme 14: Dual catalyzed C(sp2)–H arylation of 57 using DMQA 55 as the red-light-absorbing photocatalyst.
Scheme 15: Red-light-mediated aerobic oxidation of arylboronic acids 59 into phenols 60 via the use of DMQA as...
Figure 14: Red-light-photocatalyzed reactions proposed by Gianetti et al. using DMQA as the photocatalyst.
Scheme 16: Simultaneous release of NO and production of superoxide (O2•−) and their combination yielding the p...
Figure 15: Palladium porphyrin complex as the photoredox catalyst and the NO releasing substrate are linked in...
Scheme 17: Uncaging of compound 69 which is a microtubule depolymerizing agent using near IR irradiation. The ...
Scheme 18: Photochemical uncaging of drugs protected with a phenylboronic acid derivative using near IR irradi...
Scheme 19: Photoredox catalytical generation of aminyl radicals with near IR irradiation for the transfer of b...
Scheme 20: Photoredox catalytical fluoroalkylation of tryptophan moieties.
Figure 16: Simultaneous absorption of two photons of infrared light of low energy enables electronic excitatio...
Scheme 21: Uncaging Ca2+ ions using two-photon excitation with near infrared light.
Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis
- Remi Peters,
- Levy A. Charleston,
- Karinan van Eck,
- Teun van Berlo and
- Daniela A. Wilson
Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5
- Remi Peters Levy A. Charleston Karinan van Eck Teun van Berlo Daniela A. Wilson Institute of Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands 10.3762/bjoc.21.5 Abstract Polysarcosine emerges as a promising alternative to polyethylene glycol (PEG
- glutamate); polysarcosine; shape transformation; stomatocyte; supramolecular chemistry; Introduction Polymeric vesicles represent a promising candidate for usage in drug delivery systems due to their facile assembly and ability to provide a stable soft interface. Among these materials, polyethylene glycol
Graphical Abstract
Scheme 1: i) Synthesis of benzyl glutamate NCA using phosgene and propylene oxide as a scavenger. ii) Ring-op...
Figure 1: i) The PBLG-PSar block copolymers are dissolved in DMF and then assembled though the solvent-exchan...
Figure 2: Progression of shape transformation of PSar-PBLG vesicles at 70 °C (scalebar 0.5 µm). a) Initial (0...
Figure 3: The temperature-dependent behavior of vesicles and shape Transformation: a) Thermograph of PBLG-PSa...
Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures
- Yosuke Akae
Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252
- generally comprises a linear polymer-chain-like polyethylene glycol (PEG) and many rings, the loss of a few rings at the end-capping step is not expected to cause a severe issue during polyrotaxane synthesis, as applicable in small-rotaxane-molecule synthesis. Harada and Kamachi first synthesized
- depended on the cavity size, the same as small-molecule inclusion. For example, PEG forms stable pseudopolyrotaxane structures with α, β, and γ-CDs, although polypropylene glycol (PPG) only forms a stable pseudopolyrotaxane structure with β-CD [41]. In addition to these linear polymer chains, various types
Graphical Abstract
Figure 1: Overview of the CD-based rotaxane as a polymer material covered in this review.
Figure 2: CD structure.
Figure 3: Typical pathway for synthesizing CD-based rotaxanes.
Scheme 1: (A) Synthesis of α-CD-based [2]rotaxane via a metal–ligand complex. (B) Chemical structures of meth...
Scheme 2: Synthesis of α-CD-based polyrotaxane.
Scheme 3: Facile [3]rotaxane synthesis by the urea end-capping method.
Figure 4: (A) Single-crystal structure of α-CD-based [3]rotaxane 3 and PMα-CD-based [3]rotaxane 4. (B) Schema...
Figure 5: Structural control of CD-based [2]rotaxane via (A) light irradiation and (B) light irradiation and ...
Figure 6: Relationship among the plus–minus signs of ICD, the position of the guest molecule, and the axis of...
Figure 7: Structural control of CD-based rotaxane via (A) redox reaction and (B) in a solvent.
Scheme 4: (A) Synthesis of pseudopolyrotaxane bearing an ABA triblock copolymer as an axle. (B) Two synthetic...
Scheme 5: Slippage of size-complementary rotaxanes.
Figure 8: (A) Reversible formation of the CD-based [2]rotaxane. (B) Deslipping reaction of the CD-based size-...
Figure 9: (A) Chemical structures of [3]rotaxanes 2 and 3. (B) Schematic of the deslipping reaction of [3]rot...
Figure 10: (A) Modification of the axle ends of [3]rotaxane by (1) bromination and (2) the Suzuki coupling rea...
Figure 11: (A) ICD spectra of [3]rotaxanes bearing acylated (top) and conventional (bottom) CDs. (B) Schematic...
Figure 12: Synthesis of macromolecular[3]rotaxane via a size-complementary protocol.
Figure 13: Conjugated polymer insulated by (A) β-CD. (B) Triphenylamine-substituted β-CD.
Figure 14: Synthesis of the VSC and successive rotaxane-crosslinked polymer (RCP) preparation.
Figure 15: (A) Chemical structure of the [3]rotaxane crosslinker (RC). (B) Schematic of the synthesis and de-c...
Figure 16: (A) Random vinylation of the CD-based [3]rotaxane; (B) Schematic of the reaction between α-CD and m...
Figure 17: (A) Aggregation of CD-based [3]rotaxane. (B) Schematic of the plausible mechanism of the aggregatio...
Copper-catalyzed yne-allylic substitutions: concept and recent developments
- Shuang Yang and
- Xinqiang Fang
Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232
- Shuang Yang Xinqiang Fang State Key Laboratory of Structural Chemistry, and Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences, Fuzhou
Graphical Abstract
Scheme 1: Copper-catalyzed allylic and yne-allylic substitution.
Scheme 2: Challenges in achieving highly selective yne-allylic substitution.
Scheme 3: Yne-allylic substitutions using indoles and pyroles.
Scheme 4: Yne-allylic substitutions using amines.
Scheme 5: Yne-allylic substitution using 1,3-dicarbonyls.
Scheme 6: Postulated mechanism via copper acetylide-bonded allylic cation.
Scheme 7: Amine-participated asymmetric yne-allylic substitution.
Scheme 8: Asymmetric decarboxylative yne-allylic substitution.
Scheme 9: Asymmetric yne-allylic alkoxylation and alkylation.
Scheme 10: Proposed mechanism for Cu(I) system.
Scheme 11: Asymmetric yne-allylic dialkylamination.
Scheme 12: Proposed mechanism of yne-allylic dialkylamination.
Scheme 13: Asymmetric yne-allylic sulfonylation.
Scheme 14: Proposed mechanism of yne-allylic sulfonylation.
Scheme 15: Aymmetric yne-allylic substitutions using indoles and indolizines.
Scheme 16: Double yne-allylic substitutions using pyrrole.
Scheme 17: Proposed mechanism of yne-allylic substitution using electron-rich arenes.
Scheme 18: Aymmetric yne-allylic monofluoroalkylations.
Scheme 19: Proposed mechanism.
Scheme 20: Aymmetric yne-allylic substitution of yne-allylic esters with anthrones.
Scheme 21: Aymmetric yne-allylic substitution of yne-allylic esters with coumarins.
Scheme 22: Aymmetric yne-allylic substitution of with coumarins by Lin.
Scheme 23: Proposed mechanism.
Scheme 24: Amination by alkynylcopper driven dearomatization and rearomatization.
Scheme 25: Arylation by alkynylcopper driven dearomatization and rearomatization.
Scheme 26: Remote substitution/cyclization/1,5-H shift process.
Scheme 27: Proposed mechanism.
Scheme 28: Arylation or amination by alkynylcopper driven dearomatization and rearomatization.
Scheme 29: Remote nucleophilic substitution of 5-ethynylthiophene esters.
Scheme 30: Proposed mechanism.
Scheme 31: [4 + 1] annulation of yne-allylic esters and cyclic 1,3-dicarbonyls.
Scheme 32: Asymmetric [4 + 1] annulation of yne-allylic esters.
Scheme 33: Proposed mechanism.
Scheme 34: Asymmetric [3 + 2] annulation of yne-allylic esters.
Scheme 35: Postulated annulation step.
Scheme 36: [4 + 1] Annulations of vinyl ethynylethylene carbonates and 1,3-dicarbonyls.
Scheme 37: Proposed mechanism.
Scheme 38: Formal [4 + 1] annulations with amines.
Scheme 39: Formal [4 + 2] annulations with hydrazines.
Scheme 40: Proposed mechanism.
Scheme 41: Dearomative annulation of 1-naphthols and yne-allylic esters.
Scheme 42: Dearomative annulation of phenols or 2-naphthols and yne-allylic esters.
Scheme 43: Postulated annulation mechanism.
Scheme 44: Dearomative annulation of phenols or 2-naphthols.
Scheme 45: Dearomative annulation of indoles.
Scheme 46: Postulated annulation step.
Scheme 47: Asymmetric [4 + 1] cyclization of yne-allylic esters with pyrazolones.
Scheme 48: Proposed mechanism.
Scheme 49: Construction of C–C axially chiral arylpyrroles.
Scheme 50: Construction of C–N axially chiral arylpyrroles.
Scheme 51: Construction of chiral arylpyrroles with 1,2-di-axial chirality.
Scheme 52: Proposed mechanism.
Scheme 53: CO2 shuttling in yne-allylic substitution.
Scheme 54: CO2 fixing in yne-allylic substitution.
Scheme 55: Proposed mechanism.
A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis
- Nian Li,
- Ruzal Sitdikov,
- Ajit Prabhakar Kale,
- Joost Steverlynck,
- Bo Li and
- Magnus Rueping
Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214
Graphical Abstract
Figure 1: Classification of LSF reactions in this review.
Scheme 1: C(sp2)–H trifluoromethylation of heteroarenes.
Scheme 2: C(sp2)–H and C(sp3)–H alkylation of complex molecules.
Scheme 3: Electrochemical oxidation-induced intermolecular aromatic C–H sulfonamidation.
Scheme 4: Bioconjugation of tyrosine with (a) phenothiazine and (b) urazole derivatives.
Scheme 5: Electrochemical iodoamination of indoles using unactivated amines.
Scheme 6: Allylic C(sp3)–H aminations with sulfonamides.
Scheme 7: Electrochemical benzylic oxidation of C–H bonds.
Scheme 8: Site-selective electrooxidation of methylarenes to aromatic acetals.
Scheme 9: Electrochemical activation of C–H by electron-deficient W2C nanocrystals.
Scheme 10: α-Acyloxy sulfide preparation via C–H/OH cross-dehydrogenative coupling.
Scheme 11: Aromatic C–H-bond thiolation.
Scheme 12: C(sp2)–H functionalization for the installation of sulfonamide groups.
Scheme 13: Preparation of (hetero)aryl chlorides and vinyl chloride with 1,2-dichloroethane. aCu(OAc)2 (0.05 e...
Scheme 14: Electrochemical dual-oxidation enables access to α-chlorosulfoxides.
Scheme 15: Regio- and chemoselective formyloxylation–bromination/chlorination/trifluoromethylation of alkenes.
Scheme 16: Aziridine formation by coupling amines and alkenes.
Scheme 17: Formation of iminosulfide ethers via difunctionalization of an isocyanide.
Scheme 18: Synthesis of 1,3-difunctionalized molecules via C–C-bond cleavage of arylcyclopropane.
Scheme 19: Electrooxidative amino- and oxyselenation of alkenes. VBImBr = 1-butyl-3-vinylimidazolium bromide.
Scheme 20: Electrooxidative dehydrogenative [4 + 2] annulation of indole derivatives.
Scheme 21: Electrochemical cyclization combined with alkoxylation of triticonazole.
Scheme 22: Electrochemically tuned oxidative [4 + 2] annulation of olefins with hydroxamic acids.
Scheme 23: Electrosynthesis of indole derivatives via cyclization of 2-ethynylanilines.
Scheme 24: Allylic C–H oxidation of mono-, di-, and sesquiterpenes.
Scheme 25: Oxidation of unactivated C–H bonds.
Scheme 26: Fluorination of C(sp3)–H bonds. rAP = rapid alternating polarity.
Scheme 27: C(sp3)–H α-cyanation of secondary piperidines.
Scheme 28: Selective electrochemical hydrolysis of hydrosilanes to silanols.
Scheme 29: Organocatalytic electrochemical amination of benzylic C–H bonds.
Scheme 30: Iodide ion-initiated anodic oxidation reactions.
Scheme 31: Mn(III/IV) electro-catalyzed C(sp3)–H azidation.
Scheme 32: Tailored cobalt–salen complexes enable electrocatalytic intramolecular allylic C–H functionalizatio...
Scheme 33: Cobalt–salen complexes-induced electrochemical (cyclo)additions.
Scheme 34: Electrochemical 1,2-diarylation of alkenes enabled by direct dual C–H functionalization of electron...
Scheme 35: Cobalt-electrocatalyzed atroposelective C–H annulation.
Scheme 36: Nickel-electrocatalyzed C(sp2)–H alkoxylation with secondary alcohols.
Scheme 37: Nickel-catalyzed electrochemical enantioselective amination.
Scheme 38: Ruthenium-electrocatalyzed C(sp2)–H mono- and diacetoxylation.
Scheme 39: Rhodium(III)-catalyzed aryl-C–H phosphorylation enabled by anodic oxidation-induced reductive elimi...
Scheme 40: Asymmetric Lewis-acid catalysis for the synthesis of non-racemic 1,4-dicarbonyl compounds.
Scheme 41: Electrochemical enantioselective C(sp3)–H alkenylation.
Scheme 42: Palladium-catalyzed electrochemical dehydrogenative cross-coupling.
Scheme 43: Ir-electrocatalyzed vinylic C(sp2)–H activation for the annulation between acrylic acids and alkyne...
Scheme 44: Electrochemical gold-catalyzed C(sp3)–C(sp) coupling of alkynes and arylhydrazines.
Scheme 45: Photoelectrochemical alkylation of C–H heteroarenes using organotrifluoroborates.
Scheme 46: Mn-catalyzed photoelectro C(sp3)–H azidation.
Scheme 47: Photoelectrochemical undirected C–H trifluoromethylations of (Het)arenes.
Scheme 48: Photoelectrochemical dehydrogenative cross-coupling of heteroarenes with aliphatic C–H bonds.
Scheme 49: C–H amination via photoelectrochemical Ritter-type reaction.
Scheme 50: Photoelectrochemical multiple oxygenation of C–H bonds.
Scheme 51: Accelerated C(sp3)–H heteroarylations by the f-EPC system.
Scheme 52: Photoelectrochemical cross-coupling of amines.
Scheme 53: Birch electroreduction of arenes. GSW = galvanized steel wire.
Scheme 54: Electroreductive deuterations.
Scheme 55: Chemoselective electrosynthesis using rapid alternating polarity.
Scheme 56: Electroreductive olefin–ketone coupling.
Scheme 57: Electroreductive approach to radical silylation.
Scheme 58: Electrochemical borylation of alkyl halides. CC = carbon close.
Scheme 59: Radical fluoroalkylation of alkenes.
Scheme 60: Electrochemical defluorinative hydrogenation/carboxylation.
Scheme 61: Electrochemical decarboxylative olefination.
Scheme 62: Electrochemical decarboxylative Nozaki–Hiyama–Kishi coupling.
Scheme 63: Nickel-catalyzed electrochemical reductive relay cross-coupling.
Scheme 64: Electrochemical chemo- and regioselective difunctionalization of 1,3-enynes.
Scheme 65: Electrocatalytic doubly decarboxylative crosscoupling.
Scheme 66: Electrocatalytic decarboxylative crosscoupling with aryl halides.
Scheme 67: Nickel-catalyzed electrochemical reductive coupling of halides.
Scheme 68: Nickel-electrocatalyzed enantioselective carboxylation with CO2.
Scheme 69: Reductive electrophotocatalysis for borylation.
Scheme 70: Electromediated photoredox catalysis for selective C(sp3)–O cleavages of phosphinated alcohols to c...
Scheme 71: Stereoselective electro-2-deoxyglycosylation from glycals. MFE = methyl nonafluorobutyl ether.
Scheme 72: Electrochemical peptide modifications.
Scheme 73: Electrochemical α-deuteration of amides.
Scheme 74: Electrochemical synthesis of gem-diselenides.
Scheme 75: Site-selective electrochemical aromatic C–H amination.
Scheme 76: Electrochemical coupling of heteroarenes with heteroaryl phosphonium salts.
Scheme 77: Redox-neutral strategy for the dehydroxyarylation reaction.
Scheme 78: Nickel-catalyzed electrochemical C(sp3)–C(sp2) cross-coupling of benzyl trifluoroborate and halides....
Scheme 79: Paired electrocatalysis for C(sp3)–C(sp2) coupling.
Scheme 80: Redox-neutral strategy for amination of aryl bromides.
Scheme 81: Redox-neutral cross-coupling of aryl halides with weak N-nucleophiles. aProtocol with (+) RVC | RVC...
Scheme 82: Nickel-catalyzed N-arylation of NH-sulfoximines with aryl halides.
Scheme 83: Esterification of carboxylic acids with aryl halides.
Scheme 84: Electrochemically promoted nickel-catalyzed carbon–sulfur-bond formation. GFE = graphite felt elect...
Scheme 85: Electrochemical deoxygenative thiolation by Ni-catalysis. GFE = graphite felt electrode; NFE = nick...
Scheme 86: Electrochemical coupling of peptides with aryl halides.
Scheme 87: Paired electrolysis for the phosphorylation of aryl halides. GFE = graphite felt electrode, FNE = f...
Scheme 88: Redox-neutral alkoxyhalogenation of alkenes.
Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression
- Tabea Bartsch,
- Stephan Lütz and
- Katrin Rosenthal
Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192
- encoding for the target protein, amino acids and nucleoside triphosphates as substrates, an energy regeneration system and other additives such as polyethylene glycol (PEG) [9]. Although CFPS has been used and improved since the 1960s, there are challenges in its application such as low production volumes
- /ethylene glycol (EG), and choline chloride/glycerol) were chosen as additives to vary the viscosity, ion concentration, amount of macromolecules, and osmolarity in CFPS. The calculated values for the properties of the CFPS system with polymers and DES added at different concentrations are shown in Table 1
- . Although the viscosities of pure DES are relatively high (choline chloride/urea 1:2: 1200 mPa·s [28], choline chloride/glycerol 1:2: 300 mPa·s [28], betaine/ethylene glycol 1:3: 65 mPa·s [29]), the effect on viscosity when adding 2–10% to the CFPS system is almost negligible. The concentration of inorganic
Graphical Abstract
Figure 1: CFPS of sfGFP with different technical additives at various concentrations. Experiments with 2% PEG...
Figure 2: CFPS of thscGAS-sfGFP with different technical additives at various concentrations. Experiments wit...
Electrochemical allylations in a deep eutectic solvent
- Sophia Taylor and
- Scott T. Handy
Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189
- 1:3 molar ratio of tetrabutylammonium bromide and ethylene glycol (TBAB/EG) [28]. Using the reaction of p-anisaldehyde with allyl bromide as a test case, reactions were performed using three sets of different sacrificial electrodes as well as non-sacrificial graphite. As can be seen in Table 1, tin
- partial solubility of ethylene glycol in methoxycyclopentane as ethylene glycol could be clearly seen in the 1H NMR spectrum of the crude reaction extracts. It should also be noted that the lower isolated yields most likely reflect mechanical losses during extraction and chromatographic separation as the
- much less expensive and is particularly well known and frequently used in DESs. It is known that choline chloride and ethylene glycol will also form a DES when combined in a 1:2 molar ratio [49]. This solvent is much more viscous than the TBAB/EG one, and an initial attempt to use the same 20 mA
The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)
- Cristina Martini,
- Muhammad Idham Darussalam Mardjan and
- Andrea Basso
Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162
- on different substrates, the conditions were similar: 20 mol % of the catalyst, ethanol as solvent at 80 °C in the first case, 30 mol % of catalyst, ethylene glycol at 90 °C in the second case; however, a striking difference appears when the reaction was carried out in the absence of silver catalyst
- . Sashidhara et al. reported no conversion, while Liu et al. reported a 58% yield of the GBB product, postulating the ability of ethylene glycol to function as an activator (through hydrogen bonding) and a facilitator of proton transfer. After this discovery, ethylene glycol has never been employed in GBB
- reactions, if we exclude a 96-member library of GBB adducts reported very recently by Dömling et al. [9]. In this case, however, Sc(OTf)3 was used as the catalyst and the choice for ethylene glycol was dictated by the need to have a polar solvent with a high boiling temperature. Shankar et al., however
Graphical Abstract
Scheme 1: Mechanism of the GBB reaction.
Scheme 2: Comparison of the performance of Sc(OTf)3 with some RE(OTf)3 in a model GBB reaction. Conditions: a...
Scheme 3: Comparison of the performance of various Brønsted acid catalysts in the synthesis of GBB adduct 6. ...
Scheme 4: Synthesis of Brønsted acidic ionic liquid catalyst 7. Conditions: a) neat, 60 °C, 24 h; b) TfOH, DC...
Scheme 5: Aryliodonium derivatives as organic catalysts in the GBB reaction. In the box the proposed binding ...
Scheme 6: DNA-encoded GBB reaction in micelles made of amphiphilic polymer 13. Conditions: a) 13 (50 equiv), ...
Scheme 7: GBB reaction catalyzed by cyclodextrin derivative 14. Conditions: a) 14 (1 mol %), water, 100 °C, 4...
Scheme 8: Proposed mode of activation of CALB. a) activation of the substrates; b) activation of the imine; c...
Scheme 9: One-pot GBB reaction–Suzuki coupling with a bifunctional hybrid biocatalyst. Conditions: a) Pd(0)-C...
Scheme 10: GBB reaction employing 5-HMF (23) as carbonyl component. Conditions: a) TFA (20 mol %), EtOH, 60 °C...
Scheme 11: GBB reaction with β-C-glucopyranosyl aldehyde 26. Conditions: a) InCl3 (20 mol %), MeOH, 70 °C, 2–3...
Scheme 12: GBB reaction with diacetylated 5-formyldeoxyuridine 29, followed by deacetylation of GBB adduct 30....
Scheme 13: GBB reaction with glycal aldehydes 32. Conditions: a) HFIP, 25 °C, 2–4 h.
Scheme 14: Vilsmeier–Haack formylation of 6-β-acetoxyvouacapane (34) and subsequent GBB reaction. Conditions: ...
Scheme 15: GBB reaction of 4-formlyl-PCP 37. Conditions: a) HOAc or HClO4, MeOH/DCM (2:3), rt, 3 d.
Scheme 16: GBB reaction with HexT-aldehyde 39. Conditions: a) 39 (20 nmol) and amidine (20 μmol), MeOH, rt, 6 ...
Scheme 17: GBB reaction of 2,4-diaminopirimidine 41. Conditions: a) Sc(OTf)3 (20 mol %), MeCN, 120 °C (MW), 1 ...
Scheme 18: Synthesis of N-edited guanine derivatives from 3,6-diamine-1,2,4-triazin-5-one 44. Conditions: a) S...
Scheme 19: Synthesis of 2-aminoimidazoles 49 by a Mannich-3CR followed by a one-pot intramolecular oxidative a...
Scheme 20: On DNA Suzuki–Miyaura reaction followed by GBB reaction. Conditions: a) CsOH, sSPhos-Pd-G2; b) AcOH...
Scheme 21: One-pot cascade synthesis of 5-iminoimidazoles. Conditions: a) Na2SO4, DMF, 220 °C (MW).
Scheme 22: GBB reaction of 5-amino-1H-imidazole-4-carbonile 57. Conditions: a) HClO4 (5 mol %), MeOH, rt, 24 h....
Scheme 23: One-pot cascade synthesis of indole-imidazo[1,2,a]pyridine hybrids. In blue the structural motif in...
Scheme 24: One-pot cascade synthesis of fused polycyclic indoles 67 or 69 from indole-3-carbaldehyde. Conditio...
Scheme 25: One-pot cascade synthesis of linked- and bridged polycyclic indoles from indole-2-carbaldehyde (70)...
Scheme 26: One-pot cascade synthesis of pentacyclic dihydroisoquinolines (X = N or CH). In blue the structural...
Scheme 27: One-pot stepwise synthesis of imidazopyridine-fused benzodiazepines 85. Conditions: a) p-TsOH (20 m...
Scheme 28: One-pot stepwise synthesis of benzoxazepinium-fused imidazothiazoles 89. Conditions: a) Yb(OTf)3 (2...
Scheme 29: One-pot stepwise synthesis of fused imidazo[4,5,b]pyridines 95. Conditions: a) HClO4, MeOH, rt, ove...
Scheme 30: Synthesis of heterocyclic polymers via the GBB reaction. Conditions: a) p-TsOH, EtOH, 70 °C, 24 h.
Scheme 31: One-pot multicomponent reaction towards the synthesis of covalent organic frameworks via the GBB re...
Scheme 32: One-pot multicomponent reaction towards the synthesis of covalent organic frameworks via the GBB re...
Scheme 33: GBB-like multicomponent reaction towards the synthesis of benzothiazolpyrroles (X = S) and benzoxaz...
Scheme 34: GBB-like multicomponent reaction towards the formation of imidazo[1,2,a]pyridines. Conditions: a) I2...
Scheme 35: Post-functionalization of GBB products via Ugi reaction. Conditions a) HClO4, DMF, rt, 24 h; b) MeO...
Scheme 36: Post-functionalization of GBB products via Click reaction. Conditions: a) solvent-free, 150 °C, 24 ...
Scheme 37: Post-functionalization of GBB products via cascade alkyne–allene isomerization–intramolecular nucle...
Scheme 38: Post-functionalization of GBB products via metal-catalyzed intramolecular N-arylation. In red and b...
Scheme 39: Post-functionalization of GBB products via isocyanide insertion (X = N or CH). Conditions: a) HClO4...
Scheme 40: Post-functionalization of GBB products via intramolecular nucleophilic addition to nitriles. Condit...
Scheme 41: Post-functionalization of GBB products via Pictet–Spengler cyclization. Conditions: a) 4 N HCl/diox...
Scheme 42: Post-functionalization of GBB products via O-alkylation. Conditions: a) TFA (20 mol %), EtOH, 120 °...
Scheme 43: Post-functionalization of GBB products via macrocyclization (X = -CH2CH2O-, -CH2-, -(CH2)4-). Condi...
Figure 1: Antibacterial activity of GBB-Ugi adducts 113 on both Gram-negative and Gram-positive strains.
Scheme 44: GBB multicomponent reaction using trimethoprim as the precursor. Conditions: a) Yb(OTf)3 or Y(OTf)3...
Figure 2: Antibacterial activity of GBB adducts 152 against MRSA and VRE; NA = not available.
Figure 3: Antibacterial activity of GBB adduct 153 against Leishmania amazonensis promastigotes and amastigot...
Figure 4: Antiviral and anticancer evaluation of the GBB adducts 154a and 154b. In vitro antiproliferative ac...
Figure 5: Anticancer activity of the GBB-furoxan hybrids 145b, 145c and 145d determined through antiprolifera...
Scheme 45: Synthesis and anticancer activity of the GBB-gossypol conjugates. Conditions: a) Sc(OTf)3 (10 mol %...
Figure 6: Anticancer activity of polyheterocycles 133a and 136a against human neuroblastoma. Clonogenic assay...
Figure 7: Development of GBB-adducts 158a and 158b as PD-L1 antagonists. HTRF assays were carried out against...
Figure 8: Development of imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines as TDP1 inhibitors. The SMM meth...
Figure 9: GBB adducts 164a–c as anticancer through in vitro HDACs inhibition assays. Additional cytotoxic ass...
Figure 10: GBB adducts 165, 166a and 166b as anti-inflammatory agents through HDAC6 inhibition; NA = not avail...
Scheme 46: GBB reaction of triphenylamine 167. Conditions: a) NH4Cl (10 mol %), MeOH, 80 °C (MW), 1 h.
Scheme 47: 1) Modified GBB-3CR. Conditions: a) TMSCN (1.0 equiv), Sc(OTf)3 (0.2 equiv), MeOH, 140 °C (MW), 20 ...
Scheme 48: GBB reaction to assemble imidazo-fused heterocycle dimers 172. Conditions: a) Sc(OTf)3 (20 mol %), ...
Figure 11: Model compounds 173 and 174, used to study the acid/base-triggered reversible fluorescence response...
Benzylic C(sp3)–H fluorination
- Alexander P. Atkins,
- Alice C. Dean and
- Alastair J. J. Lennox
Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137
- achieved. Product 21 could be resubjected to the reaction conditions, affording difluoride 22 in 46% yield. Metal fluorides are an economical source of nucleophilic fluorine, but are sparingly soluble in organic solvents. To overcome this, in 2012, Fuchigami and co-workers used polyethylene glycol (PEG) to
Graphical Abstract
Figure 1: A) Benzylic fluorides in bioactive compounds, with B) the relative BDEs of different benzylic C–H b...
Figure 2: Base-mediated benzylic fluorination with Selectfluor.
Figure 3: Sonochemical base-mediated benzylic fluorination with Selectfluor.
Figure 4: Mono- and difluorination of nitrogen-containing heteroaromatic benzylic substrates.
Figure 5: Palladium-catalysed benzylic C–H fluorination with N-fluoro-2,4,6-trimethylpyridinium tetrafluorobo...
Figure 6: Palladium-catalysed, PIP-directed benzylic C(sp3)–H fluorination of α-amino acids and proposed mech...
Figure 7: Palladium-catalysed monodentate-directed benzylic C(sp3)–H fluorination of α-amino acids.
Figure 8: Palladium-catalysed bidentate-directed benzylic C(sp3)–H fluorination.
Figure 9: Palladium-catalysed benzylic fluorination using a transient directing group approach. Ratio refers ...
Figure 10: Outline for benzylic C(sp3)–H fluorination via radical intermediates.
Figure 11: Iron(II)-catalysed radical benzylic C(sp3)–H fluorination using Selectfluor.
Figure 12: Silver and amino acid-mediated benzylic fluorination.
Figure 13: Copper-catalysed radical benzylic C(sp3)–H fluorination using NFSI.
Figure 14: Copper-catalysed C(sp3)–H fluorination of benzylic substrates with electrochemical catalyst regener...
Figure 15: Iron-catalysed intramolecular fluorine-atom-transfer from N–F amides.
Figure 16: Vanadium-catalysed benzylic fluorination with Selectfluor.
Figure 17: NDHPI-catalysed radical benzylic C(sp3)–H fluorination with Selectfluor.
Figure 18: Potassium persulfate-mediated radical benzylic C(sp3)–H fluorination with Selectfluor.
Figure 19: Benzylic fluorination using triethylborane as a radical chain initiator.
Figure 20: Heterobenzylic C(sp3)–H radical fluorination with Selectfluor.
Figure 21: Benzylic fluorination of phenylacetic acids via a charge-transfer complex. NMR yields in parenthese...
Figure 22: Oxidative radical photochemical benzylic C(sp3)–H strategies.
Figure 23: 9-Fluorenone-catalysed photochemical radical benzylic fluorination with Selectfluor.
Figure 24: Xanthone-photocatalysed radical benzylic fluorination with Selectfluor II.
Figure 25: 1,2,4,5-Tetracyanobenzene-photocatalysed radical benzylic fluorination with Selectfluor.
Figure 26: Xanthone-catalysed benzylic fluorination in continuous flow.
Figure 27: Photochemical phenylalanine fluorination in peptides.
Figure 28: Decatungstate-photocatalyzed versus AIBN-initiated selective benzylic fluorination.
Figure 29: Benzylic fluorination using organic dye Acr+-Mes and Selectfluor.
Figure 30: Palladium-catalysed benzylic C(sp3)–H fluorination with nucleophilic fluoride.
Figure 31: Manganese-catalysed benzylic C(sp3)–H fluorination with AgF and Et3N·3HF and proposed mechanism. 19...
Figure 32: Iridium-catalysed photocatalytic benzylic C(sp3)–H fluorination with nucleophilic fluoride and N-ac...
Figure 33: Iridium-catalysed photocatalytic benzylic C(sp3)–H fluorination with TBPB HAT reagent.
Figure 34: Silver-catalysed, amide-promoted benzylic fluorination via a radical-polar crossover pathway.
Figure 35: General mechanism for oxidative electrochemical benzylic C(sp3)–H fluorination.
Figure 36: Electrochemical benzylic C(sp3)–H fluorination with HF·amine reagents.
Figure 37: Electrochemical benzylic C(sp3)–H fluorination with 1-ethyl-3-methylimidazolium trifluoromethanesul...
Figure 38: Electrochemical benzylic C(sp3)–H fluorination of phenylacetic acid esters with HF·amine reagents.
Figure 39: Electrochemical benzylic C(sp3)–H fluorination of triphenylmethane with PEG and CsF.
Figure 40: Electrochemical benzylic C(sp3)–H fluorination with caesium fluoride and fluorinated alcohol HFIP.
Figure 41: Electrochemical secondary and tertiary benzylic C(sp3)–H fluorination. GF = graphite felt. DCE = 1,...
Figure 42: Electrochemical primary benzylic C(sp3)–H fluorination of electron-poor toluene derivatives. Ring f...
Figure 43: Electrochemical primary benzylic C(sp3)–H fluorination utilizing pulsed current electrolysis.
Synthetic applications of the Cannizzaro reaction
- Bhaskar Chatterjee,
- Dhananjoy Mondal and
- Smritilekha Bera
Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120
- reaction of tetraethylene glycol (TEG) was accomplished by Vida et al. [29] using a barium compound. Different types of solvents were also applied for the Cannizzaro reactions. The use of aqueous or solvent-free conditions has played pivotal roles in terms of environmental consciousness and a greener
- Cannizzaro reaction of dialdehyde 23, synthesized from tetraethylene glycol (TEG) 22. The dialdehyde 23 underwent a clean desymmetrization to form the hydroxy carboxylic acid derivative 24. The reaction was mediated by Ba2+ which perfectly bound the TEG and allowed the aldehyde functionalities to be placed
- ethylene glycol units of different chain lengths ranging from 2–5 (25, 26, and 27), by varying the aromatic substitution in the ortho, meta and para-positions and finally obtained the desymmetrized products 28, 29, and 30 in good to excellent yields (Scheme 15). This has been effectively depicted in the
Graphical Abstract
Figure 1: Types and mechanism of the Cannizzaro reaction.
Figure 2: Various approaches of the Cannizzaro reaction.
Figure 3: Representative molecules synthesized via the Cannizzaro reaction.
Scheme 1: Intramolecular Cannizzaro reaction of aryl glyoxal hydrates using TOX catalysts.
Scheme 2: Intramolecular Cannizzaro reaction of aryl methyl ketones using ytterbium triflate/selenium dioxide....
Scheme 3: Intramolecular Cannizzaro reaction of aryl glyoxals using Cr(ClO4)3 as catalyst.
Scheme 4: Cu(II)-PhBox-catalyzed asymmetric Cannizzaro reaction.
Scheme 5: FeCl3-based chiral catalyst applied for the enantioselective intramolecular Cannizzaro reaction rep...
Scheme 6: Copper bis-oxazoline-catalysed intramolecular Cannizzaro reaction and proposed mechanism.
Scheme 7: Chiral Fe catalysts-mediated enantioselective Cannizzaro reaction.
Scheme 8: Ruthenium-catalyzed Cannizzaro reaction of aromatic aldehydes.
Scheme 9: MgBr2·Et2O-assisted Cannizzaro reaction of aldehydes.
Scheme 10: LiBr-catalyzed intermolecular Cannizzaro reaction of aldehydes.
Scheme 11: γ-Alumina as a catalyst in the Cannizzaro reaction.
Scheme 12: AlCl3-mediated Cannizzaro disproportionation of aldehydes.
Scheme 13: Ru–N-heterocyclic carbene catalyzed dehydrogenative synthesis of carboxylic acids.
Figure 4: Proposed catalytic cycle for the dehydrogenation of alcohols.
Scheme 14: Intramolecular desymmetrization of tetraethylene glycol.
Scheme 15: Desymmetrization of oligoethylene glycol dialdehydes.
Scheme 16: Intramolecular Cannizzaro reaction of calix[4]arene dialdehydes.
Scheme 17: Desymmetrization of dialdehydes of symmetrical crown ethers using Ba(OH)2.
Scheme 18: Synthesis of ottelione A (proposed) via intramolecular Cannizzaro reaction.
Scheme 19: Intramolecular Cannizzaro reaction for the synthesis of pestalalactone.
Scheme 20: Synthetic strategy towards nigricanin involving an intramolecular Cannizzaro reaction.
Scheme 21: Spiro-β-lactone-γ-lactam part of oxazolomycins via aldol crossed-Cannizzaro reaction.
Scheme 22: Synthesis of indole alkaloids via aldol crossed-Cannizzaro reaction.
Scheme 23: Aldol and crossed-Cannizzaro reaction towards the synthesis of ertuliflozin.
Scheme 24: Synthesis of cyclooctadieneones using a Cannizzaro reaction.
Scheme 25: Microwave-assisted crossed-Cannizzaro reaction for the synthesis of 3,3-disubstituted oxindoles.
Scheme 26: Synthesis of porphyrin-based rings using the Cannizzaro reaction.
Scheme 27: Synthesis of phthalides and pestalalactone via Cannizarro–Tishchenko-type reaction.
Scheme 28: Synthesis of dibenzoheptalene bislactones via a double intramolecular Cannizzaro reaction.
Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents
- Ayhan Yıldırım
Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114
- importance in intramolecular Diels–Alder reactions, the effects of solvents such as glycerol, polyethylene glycol, organic carbonates, deep eutectic solvents, supercritical CO2 and H2O have recently been extensively studied [65][66][67]. Recently, attention has also been drawn to photoinduced oxidative [4
Graphical Abstract
Figure 1: Reaction yields after seven uses of SSO and average recovery of the oil.
Scheme 1: Synthesis of epoxyisoindole-7-carboxylic acids 2a–m and 2n–p.
Scheme 2: Possible side reactions of unsaturated fatty acids with maleic anhydride.
Figure 2: Coupling constants of selected protons in compound 2a and its optimized geometric structure.
Scheme 3: Equilibrium of 2n–p with maleamic acid precursors.
Figure 3: Possible mechanism for the IMDAF reaction.
Figure 4: IRC calculations of a) endo-, b) exo-transition structures and products for compound 2a (semi-empir...
Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer
- Mohd Farhan Ansari,
- Atul Kumar Maurya,
- Abhishek Kumar and
- Saravanakumar Elangovan
Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98
- polyethyleneimine derivatives by coupling ethylene glycol and ethylenediamine using manganese-pincer catalyst Mn1 (1 mol %), t-BuOK (10 mol %) in toluene at 150 °C (Scheme 21) [48]. The mechanistic investigation based on the experimental and DFT calculations suggested a BH pathway. First, dehydrogenation of the
- ethylene glycol followed by condensation with ethylenediamine generated the corresponding imine intermediates. The subsequent hydrogenation with borrowed hydrogen finally formed the polyethyleneimine product. In 2023, Royo and co-workers conveyed the N-alkylation of amines with alcohols using the bis
- hydrogenated the C=C and C=O bonds delivering the desired alkylated alcohol products (Scheme 49). Recently, Maji’s group showed environmentally benign examples of the manganese-catalyzed dehydrogenative coupling of ethylene glycol and primary alcohols producing value-added α-hydroxycarboxylic acid molecules
Graphical Abstract
Scheme 1: General scheme of the borrowing hydrogen (BH) or hydrogen auto-transfer (HA) methodology.
Scheme 2: General scheme for C–N bond formation. A) Traditional cross-couplings with alkyl or aryl halides. B...
Figure 1: Manganese pre-catalysts used for the N-alkylation of amines with alcohols.
Scheme 3: Manganese(I)-pincer complex Mn1 used for the N-alkylation of amines with alcohols and methanol.
Scheme 4: N-Methylation of amines with methanol using Mn2.
Scheme 5: C–N-Bond formation with amines and methanol using PN3P-Mn complex Mn3 reported by Sortais et al. [36]. a...
Scheme 6: Base-assisted synthesis of amines and imines with Mn4. Reaction assisted by A) t-BuOK and B) t-BuON...
Scheme 7: Coupling of alcohols and hydrazine via the HB approach reported by Milstein et al. [38]. aReaction time...
Scheme 8: Proposed mechanism for the coupling of alcohols and hydrazine catalyzed by Mn5.
Scheme 9: Phosphine-free manganese catalyst for N-alkylation of amines with alcohols reported by Balaraman an...
Scheme 10: N-Alkylation of sulfonamides with alcohols.
Scheme 11: Mn–NHC catalyst Mn6 applied for the N-alkylation of amines with alcohols. a3 mol % of Mn6 were used....
Scheme 12: N-Alkylation of amines with primary and secondary alcohols. a80 °C, b100 °C.
Scheme 13: Manganese(III)-porphyrin catalyst for synthesis of tertiary amines.
Scheme 14: Proposed mechanism for the alcohol dehydrogenation with Mn(III)-porphyrin complex Mn7.
Scheme 15: N-Methylation of nitroarenes with methanol using catalyst Mn3.
Scheme 16: Mechanism of manganese-catalyzed methylation of nitroarenes using Mn3 as the catalyst.
Scheme 17: Bidentate manganese complex Mn8 applied for the N-alkylation of primary anilines with alcohols. aOn...
Scheme 18: N-Alkylation of amines with alcohols in the presence of manganese salts and triphenylphosphine as t...
Scheme 19: N-Alkylation of diazo compounds with alcohols using catalyst Mn9.
Scheme 20: Proposed mechanism for the amination of alcohols with diazo compounds catalyzed by catalyst Mn9.
Scheme 21: Mn1 complex-catalyzed synthesis of polyethyleneimine from ethylene glycol and ethylenediamine.
Scheme 22: Bis-triazolylidene-manganese complex Mn10 for the N-alkylation of amines with alcohols.
Figure 2: Manganese complexes applied for C-alkylation reactions of ketones with alcohols.
Scheme 23: General scheme for the C–C bond formation with alcohols and ketones.
Scheme 24: Mn1 complex-catalyzed α-alkylation of ketones with primary alcohols.
Scheme 25: Mechanism for the Mn1-catalyzed alkylation of ketones with alcohols.
Scheme 26: Phosphine-free in situ-generated manganese catalyst for the α-alkylation of ketones with primary al...
Scheme 27: Plausible mechanism for the Mn-catalyzed α-alkylation of ketones with alcohols.
Scheme 28: α-Alkylation of esters, ketones, and amides using alcohols catalyzed by Mn11.
Scheme 29: Mono- and dialkylation of methylene ketones with primary alcohols using the Mn(acac)2/1,10-phenanth...
Scheme 30: Methylation of ketones with methanol and deuterated methanol.
Scheme 31: Methylation of ketones and esters with methanol. a50 mol % of t-BuOK were used, bCD3OD was used ins...
Scheme 32: Alkylation of ketones and secondary alcohols with primary alcohols using Mn4.
Scheme 33: Bidentate manganese-NHC complex Mn6 applied for the synthesis of alkylated ketones using alcohols.
Scheme 34: Mn1-catalyzed synthesis of substituted cycloalkanes by coupling diols and secondary alcohols or ket...
Scheme 35: Proposed mechanism for the synthesis of cycloalkanes via BH method.
Scheme 36: Synthesis of various cycloalkanes from methyl ketones and diols catalyze by Mn13. aReaction time wa...
Scheme 37: N,N-Amine–manganese complex (Mn13)-catalyzed alkylation of ketones with alcohols.
Scheme 38: Naphthyridine‑N‑oxide manganese complex Mn14 applied for the alkylation of ketones with alcohols. a...
Scheme 39: Proposed mechanism of the naphthyridine‑N‑oxide manganese complex (Mn14)-catalyzed alkylation of ke...
Scheme 40: α-Methylation of ketones and indoles with methanol using Mn15.
Scheme 41: α-Alkylation of ketones with primary alcohols using Mn16. aNMR yield.
Figure 3: Manganese complexes used for coupling of secondary and primary alcohols.
Scheme 42: Alkylation of secondary alcohols with primary alcohols catalyzed by phosphine-free catalyst Mn17. a...
Scheme 43: PNN-Manganese complex Mn18 for the alkylation of secondary alcohols with primary alcohols.
Scheme 44: Mechanism for the Mn-pincer catalyzed C-alkylation of secondary alcohols with primary alcohols.
Scheme 45: Upgrading of ethanol with methanol for isobutanol production.
Scheme 46: Mn-Pincer catalyst Mn19 applied for the β-methylation of alcohols with methanol. a2.0 mol % of Mn19...
Scheme 47: Functionalized ketones from primary and secondary alcohols catalyzed by Mn20. aMn20 (5 mol %), NaOH...
Scheme 48: Synthesis of γ-disubstituted alcohols and β-disubstituted ketones through Mn9-catalyzed coupling of...
Scheme 49: Proposed mechanism for the Mn9-catalyzed synthesis of γ-disubstituted alcohols and β-disubstituted ...
Scheme 50: Dehydrogenative coupling of ethylene glycol and primary alcohols catalyzed by Mn4.
Scheme 51: Mn18-cataylzed C-alkylation of unactivated esters and amides with alcohols.
Scheme 52: Alkylation of amides and esters using Mn21.
Scheme 53: α-Alkylation of nitriles with primary alcohols using in situ-generated manganese catalyst.
Scheme 54: Proposed mechanism for the α-alkylation of nitriles with primary alcohols.
Scheme 55: Mn9-catalyzed α-alkylation of nitriles with primary alcohols. a1,4-Dioxane was used as solvent, 24 ...
Figure 4: Manganese complexes used for alkylation of heterocyclic compounds.
Scheme 56: Aminomethylation of aromatic compounds with secondary amines and methanol catalyzed by Mn22.
Scheme 57: Regioselective alkylation of indolines with alcohols catalyzed by Mn9. aMn9 (4 mol %), 48 h.
Scheme 58: Proposed mechanism for the C- and N-alkylation of indolines with alcohols.
Scheme 59: C-Alkylation of methyl N-heteroarenes with primary alcohols catalyzed by Mn1. aTime was 60 h.
Scheme 60: C-Alkylation of oxindoles with secondary alcohols.
Scheme 61: Plausible mechanism for the Mn23-catalyzed C-alkylation of oxindoles with secondary alcohols.
Scheme 62: Synthesis of C-3-alkylated products by coupling alcohols with indoles and aminoalcohols.
Scheme 63: C3-Alkylation of indoles using Mn1.
Scheme 64: C-Methylation of indoles with Mn15 and methanol.
Scheme 65: α-Alkylation of 2-oxindoles with primary and secondary alcohols catalyzed by Mn25. aReaction carrie...
Scheme 66: Dehydrogenative alkylation of indolines with Mn1. aMn1 (5.0 mol %) was used.
Scheme 67: Synthesis of bis(indolyl)methane derivatives from indoles and alcohols catalyzed by Mn26. aMn26 (5....
Scheme 68: One-pot synthesis of pyrimidines via BH.
Scheme 69: Synthesis of pyrroles from alcohols and aminoalcohols using Mn4.
Scheme 70: Synthesis of pyrroles via multicomponent reaction catalyzed by Mn12.
Scheme 71: Friedländer quinoline synthesis using an in situ-generated phosphine-free manganese catalyst.
Scheme 72: Quinoline synthesis using bis-N-heterocyclic carbene-manganese catalyst Mn6.
Scheme 73: Quinoline synthesis using manganese(III)-porphyrin catalyst Mn7.
Scheme 74: Manganese-catalyzed tetrahydroquinoline synthesis via borrowing BH.
Scheme 75: Proposed mechanism for the manganese-catalyzed tetrahydroquinoline synthesis.
Scheme 76: Synthesis of C3-alkylated indoles using Mn24.
Scheme 77: Synthesis of C-3-alkylated indoles using Mn1.
Scheme 78: C–C Bond formation by coupling of alcohols and ylides.
Scheme 79: C-Alkylation of fluorene with alcohols catalyzed by Mn24.
Scheme 80: Proposed mechanism for the C-alkylation of fluorene with alcohols catalyzed by Mn24.
Scheme 81: α-Alkylation of sulfones using Mn-PNN catalyst Mn28.
Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines
- Vladislav V. Nikol’skiy,
- Mikhail E. Minyaev,
- Maxim A. Bastrakov and
- Alexey M. Starosotnikov
Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94
- group of compounds 7 should be protected prior to the attempted isoxazole ring formation. Indeed, reactions of 7a–c with ethylene glycol gave dioxolane derivatives 9a–c which were converted into isoxazolo[4,5-b]pyridines 10a–c in high yields under mild conditions (Scheme 4). The obtained result prompted
Graphical Abstract
Figure 1: Some examples of biologically active isoxazolo[4,5-b]pyridines with antibacterial [8], anticancer [12] and...
Scheme 1: Methods for the synthesis of isoxazolo[4,5-b]pyridines: (A) annulation of an isoxazole fragment to ...
Scheme 2: Synthesis of ethyl 6-R-isoxazolo[4,5-b]pyridine-3-carboxylates 4a–c.
Scheme 3: Synthesis of isonitroso compounds 7.
Scheme 4: Base-promoted cyclization of compounds 7a–c.
Scheme 5: Synthesis and rearrangement of arylhydrazones 12.
Figure 2: Biologically active analogs of compounds 13.
Figure 3: X-ray crystal structures of compounds 12c (top left; the second crystallographically unique molecul...
Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives
- Tural N. Akhmedov,
- Ajeet Kumar,
- Daken J. Starkenburg,
- Kyle J. Chesney,
- Khalil A. Abboud,
- Novruz G. Akhmedov,
- Jiangeng Xue and
- Ronald K. Castellano
Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92
- , ethanol, ethylene glycol, and diethylene glycol in the presence of excess triethylamine (Scheme 2). These products provide evidence for the in situ formation of DCPQ 7a and demonstrate its ability to undergo trapping with various nucleophiles through an SNAr mechanism. An alternate strategy was employed
- -stacking distances (≈3.2 Å) are observed between the 5b units. For 6b, this is likely due to the included solvent (ethylene glycol) that hydrogen bonds to the quinoxalinedione. Moving forward, 2b stands out as a promising candidate for future solid-state characterization and device fabrication studies
Graphical Abstract
Figure 1: Chemical structures of H-bonding N-heteroacenes synthesized by Miao et al. and Bunz et al. (a) [22,23]. Pr...
Scheme 1: Synthesis of dicyanopyrazinoquinoxaline derivatives 1a–7a.
Scheme 2: Synthesis of bis-alkoxy-substituted π-conjugated phenanthrolines 16a, 16b, 16c, and 16d.
Scheme 3: An alternative synthetic route to access 7a.
Scheme 4: Synthesis of DPQDs 1b–7b from their corresponding DCPQs 1a–7a. *THF/H2O/1,4-dioxane (4:5:1). **in s...
Figure 2: TGA of 1a–6a (a) and 1b–7b (b) obtained at 10 °C/min under nitrogen.
Figure 3: Absorption spectra (20 μM) for a) DCPQs 1a–6a and b) DPQDs 1b–7b in dimethyl sulfoxide.
Figure 4: Calculated HOMO (below) and LUMO (above) energies by DFT analysis (B3LYP/6-31+G* level of theory), ...
Figure 5: Calculated HOMO (below) and LUMO (above) energies by DFT analysis (B3LYP/6-31+G* level of theory), ...
Figure 6: Asymmetric unit of DPQD 2b with important bond lengths highlighted (a). Torsion angles of 4.33° and...
Carbonylative synthesis and functionalization of indoles
- Alex De Salvo,
- Raffaella Mancuso and
- Xiao-Feng Wu
Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87
- the presence of Ni(dme)Cl2 (a nickel(II) chloride ethylene glycol dimethyl ether complex), dtbbpy (4,4-di-tert-butyl-2,2-dipyridyl), Zn(0) and ZnI2 in DMF at 120 °C [42] (Scheme 22). The nickel catalyst catalyzed the oxidative addition and CO insertion on aryl iodide compounds, while the Zn/ZnI2
Graphical Abstract
Scheme 1: Pd(0)-catalyzed domino C,N-coupling/carbonylation/Suzuki coupling reaction for the synthesis of 2-a...
Scheme 2: Pd(0)-catalyzed single isonitrile insertion: synthesis of 1-(3-amino)-1H-indol-2-yl)-1-ketones.
Scheme 3: Pd(0)-catalyzed gas-free carbonylation of 2-alkynylanilines to 1-(1H-indol-1-yl)-2-arylethan-1-ones....
Scheme 4: Pd(II)-catalyzed heterocyclization/alkoxycarbonylation of 2-alkynylaniline imines.
Scheme 5: Pd(II)-catalyzed heterocyclization/alkoxycarbonylation of 2-alkynylanilines to N-substituted indole...
Scheme 6: Synthesis of indol-2-acetic esters by Pd(II)-catalyzed carbonylation of 1-(2-aminoaryl)-2-yn-1-ols.
Scheme 7: Pd(II)-catalyzed carbonylative double cyclization of suitably functionalized 2-alkynylanilines to 3...
Scheme 8: Indole synthesis by deoxygenation reactions of nitro compounds reported by Cenini et al. [21].
Scheme 9: Indole synthesis by reduction of nitro compounds: approach reported by Watanabe et al. [22].
Scheme 10: Indole synthesis from o-nitrostyrene compounds as reported by Söderberg and co-workers [23].
Scheme 11: Synthesis of fused indoles (top) and natural indoles present in two species of European Basidiomyce...
Scheme 12: Synthesis of 1,2-dihydro-4(3H)-carbazolones through N-heteroannulation of functionalized 2-nitrosty...
Scheme 13: Synthesis of indoles from o-nitrostyrenes by using Pd(OAc)2 and Pd(tfa)2 in conjunction with bident...
Scheme 14: Synthesis of substituted 3-alkoxyindoles via palladium-catalyzed reductive N-heteroannulation.
Scheme 15: Synthesis of 3-arylindoles by palladium-catalyzed C–H bond amination via reduction of nitroalkenes.
Scheme 16: Synthesis of 2,2′-bi-1H-indoles, 2,3′-bi-1H-indoles, 3,3′-bi-1H-indoles, indolo[3,2-b]indoles, indo...
Scheme 17: Pd-catalyzed reductive cyclization of 1,2-bis(2-nitrophenyl)ethene and 1,1-bis(2-nitrophenyl)ethene...
Scheme 18: Flow synthesis of 2-substituted indoles by reductive carbonylation.
Scheme 19: Pd-catalyzed synthesis of variously substituted 3H-indoles from nitrostyrenes by using Mo(CO)6 as C...
Scheme 20: Synthesis of indoles from substituted 2-nitrostyrenes (top) and ω-nitrostyrenes (bottom) via reduct...
Scheme 21: Synthesis of indoles from substituted 2-nitrostyrenes with formic acid as CO source.
Scheme 22: Ni-catalyzed carbonylative cyclization of 2-nitroalkynes and aryl iodides (top) and the Ni-catalyze...
Scheme 23: Mechanism of the Ni-catalyzed carbonylative cyclization of 2-nitroalkynes and aryl iodides (top) an...
Scheme 24: Route to indole derivatives through Rh-catalyzed benzannulation of heteroaryl propargylic esters fa...
Scheme 25: Pd-catalyzed cyclization of 2-(2-haloaryl)indoles reported by Yoo and co-workers [54], Guo and co-worke...
Scheme 26: Approach for the synthesis of 6H-isoindolo[2,1-a]indol-6-ones reported by Huang and co-workers [57].
Scheme 27: Zhou group’s method for the synthesis of 6H-isoindolo[2,1-a]indol-6-ones.
Scheme 28: Synthesis of 6H-isoindolo[2,1-a]indol-6-ones from o-1,2-dibromobenzene and indole derivatives by us...
Scheme 29: Pd(OAc)2-catalyzed Heck cyclization of 2-(2-bromophenyl)-1-alkyl-1H-indoles reported by Guo et al. [55]....
Scheme 30: Synthesis of indolo[1,2-a]quinoxalinone derivatives through Pd/Cu co-catalyzed carbonylative cycliz...
Scheme 31: Pd-catalyzed carbonylative cyclization of o-indolylarylamines and N-monosubstituted o-indolylarylam...
Scheme 32: Pd-catalyzed diasteroselective carbonylative cyclodearomatization of N-(2-bromobenzoyl)indoles with...
Scheme 33: Pd(0)-catalyzed synthesis of CO-linked heterocyclic scaffolds from alkene-indole derivatives and 2-...
Scheme 34: Proposed mechanism for the Pd(0)-catalyzed synthesis of CO-linked heterocyclic scaffolds.
Scheme 35: Pd-catalyzed C–H and N–H alkoxycarbonylation of indole derivatives to indole-3-carboxylates and ind...
Scheme 36: Rh-catalyzed C–H alcoxycarbonylation of indole derivatives to indole-3-carboxylates reported by Li ...
Scheme 37: Pd-catalyzed C–H alkoxycarbonylation of indole derivatives with alcohols and phenols to indole-3-ca...
Scheme 38: Synthesis of N-methylindole-3-carboxylates from N-methylindoles and phenols through metal-catalyst-...
Scheme 39: Synthesis of indol-3-α-ketoamides (top) and indol-3-amides (bottom) via direct double- and monoamin...
Scheme 40: The direct Sonogashira carbonylation coupling reaction of indoles and alkynes via Pd/CuI catalysis ...
Scheme 41: Synthesis of indole-3-yl aryl ketones reported by Zhao and co-workers [73] (path a) and Zhang and co-wo...
Scheme 42: Pd-catalyzed carbonylative synthesis of BIMs from aryl iodides and N-substituted and NH-free indole...
Scheme 43: Cu-catalyzed direct double-carbonylation and monocarbonylation of indoles and alcohols with hexaket...
Scheme 44: Rh-catalyzed direct C–H alkoxycarbonylation of indoles to indole-2-carboxylates [79] (top) and Co-catal...
Scheme 45: Pd-catalyzed carbonylation of NH free-haloindoles.
Synthesis and characterization of water-soluble C60–peptide conjugates
- Yue Ma,
- Lorenzo Persi and
- Yoko Yamakoshi
Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71
- -soluble C60 and C70 derivatives by covalently attaching biocompatible water-soluble polymers, such as polyethylene glycol (PEG) [37][38] and PVP [39]. Although these C60– and C70–polymer conjugates revealed high water-solubility, it was found that they, especially the PEG conjugates, formed micelle-like
Graphical Abstract
Figure 1: a) Synthesis of C60–oligopeptide conjugates 5a–c and b) synthesis of compound 3. Fulleropyrrolidine...
Figure 2: Structure of C60–oligo-Lys (5a), C60–oligo-Glu (5b), and C60–oligo-Arg (5c) and images of dissolved...
Figure 3: DLS diagrams of C60–peptide conjugates 5a (1 mM, in Milli-Q® water), 5b (1 mM, in Milli-Q® water or...
Figure 4: UV–vis spectra of C60–peptide conjugates 5a and 5b (20 μM in Milli-Q® water for 5a and in pH 9.0 TR...
Figure 5: 1H NMR spectrum of C60–peptide conjugate 5a in D2O (above) and of the precursor monoadduct in CDCl3...
Figure 6: 13C NMR spectrum of C60–peptide conjugate 5a in D2O and of the precursor monoadduct in CDCl3 at 150...
Figure 7: a) X-band ESR spectra of the 4-oxo-TEMP adduct with 1O2 generated by C60–oligo-Lys (5a) and rose be...
Synthesis of new representatives of A3B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations
- Victoria M. Alpatova,
- Evgeny G. Rys,
- Elena G. Kononova and
- Valentina A. Ol'shevskaya
Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70
- -dioxaoctane (21) and 1,13-diamino-4,7,10-trioxatridecane (22) in DMSO at 70 °C for 30 min to form amino-conjugates 23 and 24 in 71 and 84% yield, respectively, containing ethylene glycol linkers with terminal primary amino groups (Scheme 6). The presence of ethylene glycol residues in bioactive molecules is
Graphical Abstract
Scheme 1: Synthesis of porphyrins 2 and 3.
Scheme 2: Synthesis of carborane aminoporphyrin 5.
Scheme 3: Synthesis of carboranyl-substituted porphyrins 5–7.
Scheme 4: Synthesis of acylated carboranylporphyrins 11, 12, and 14.
Scheme 5: Synthesis of thio-substituted carboranylporphyrins 18–20.
Scheme 6: Synthesis of amino-substituted carboranylporphyrins 23, 24, and 26.
Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization
- Senze Qiao,
- Zhongyu Cheng and
- Fuzhuo Li
Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66
- and promote the utilization of TE domains as biocatalysts with tremendous potential. To this purpose, Walsh and co-workers developed the 2nd generation of tyrocidine chemoenzymatic approach utilizing a linear peptide immobilized on the solid-phase support poly(ethylene glycol) acrylate (PEGA) with a
- exhibits a cyclization activity against a peptide methyl ester that is feeble but readily detectable [61]. This finding indicates that SurE has a high tolerance for leaving groups. In the light of this property, Wakimoto, Matsuda, and co-workers discovered that ethylene glycol (EG) can act as a linker on
- manner catalyzed by homolog WolJ [63] and SurE G235L (Scheme 5b). Additionally, the above mentioned type I TE, TycC TE, can also tolerate ethylene glycol as a leaving group and gave tyrocidine A (1) in 70% yield, indicating that this convenient bifunctional linker may have a comparable applied range to N
Graphical Abstract
Scheme 1: Brief introduction of thioesterase (TE) domain. (a) NRPS and PKS assembly lines. (b) Mechanism of T...
Scheme 2: Chemoenzymatic synthesis of tyrocidine A and its analogs. (a) First-gen chemoenzymatic synthesis of...
Scheme 3: Representative examples of NAC-activated thioesters-mediated biocatalytic macrolactamization.
Scheme 4: Chemoenzymatic synthesis of CDA, daptomycin and their analogs. (a) Biocatalytic macrocyclization of...
Scheme 5: Chemoenzymatic synthesis of surugamide B and related natural products. (a) Three synthetic strategi...
Scheme 6: Chemoenzymatic synthesis of the pikromycins. (a) Macrocyclization of 10-deoxymethynolide catalyzed ...
Scheme 7: Chemoenzymatic synthesis of the juevnimicins.
Scheme 8: Chemoenzymatic synthesis of the cryptophycins.
