Search for "three-component reaction" in Full Text gives 138 result(s) in Beilstein Journal of Organic Chemistry.
Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102
Graphical Abstract
Scheme 1: In situ generation of imidazolylidene carbene.
Scheme 2: Hg(II) complex of NHC.
Scheme 3: Isolable and bottlable carbene reported by Arduengo [3].
Scheme 4: First air-stable carbene synthesized by Arduengo in 1992 [5].
Figure 1: General structure of an NHC.
Figure 2: Stabilization of an NHC by donation of the lone pair electrons into the vacant p-orbital (LUMO) at ...
Figure 3: Abnormal NHC reported by Bertrand [8,9].
Figure 4: Cu(d) orbital to σ*C-N(NHC) interactions in NHC–CuX complexes computed at the B3LYP/def2-SVP level ...
Figure 5: Molecular orbital contributions to the NHC–metal bond.
Scheme 5: Synthesis of NHC–Cu(I) complexes by deprotonation of NHC precursors with a base.
Scheme 6: Synthesis of [NHC–CuX] complexes.
Scheme 7: Synthesis of [(ICy)CuX] and [(It-Bu)CuX] complexes.
Scheme 8: Synthesis of iodido-bridged copper–NHC complexes by deprotonation of benzimidazolium salts reported...
Scheme 9: Synthesis of copper complexes by deprotonation of triazolium salts.
Scheme 10: Synthesis of thiazolylidene–Cu(I) complex by deprotonation with KOt-Bu.
Scheme 11: Preparation of NHC–Cu(I) complexes.
Scheme 12: Synthesis of methylmalonic acid-derived anionic [(26a,b)CuCl]Li(THF)2 and zwitterionic (28) heterol...
Scheme 13: Synthesis of diaminocarbene and diamidocarbene (DAC)–Cu(I) complexes.
Scheme 14: Synthesis of the cationic (NHC)2Cu(I) complex 39 from benzimidazolium salts 38 with tetrakis(aceton...
Scheme 15: Synthesis of NHC and ADC (acyclic diamino carbenes) Cu(I) hexamethyldisilazide complexes reported b...
Scheme 16: Synthesis of NHC–copper(I) complexes using an acetylacetonate-functionalized imidazolium zwitterion...
Scheme 17: Synthesis of NHC–Cu(I) complexes through deprotonation of azolium salts with Cu2O.
Scheme 18: Synthesis of NHC–CuBr complex through deprotonation with Cu2O reported by Kolychev [31].
Scheme 19: Synthesis of chiral NHC–CuBr complexes from phenoxyimine-imidazolium salts reported by Douthwaite a...
Scheme 20: Preparation of linear neutral NHC–CuCl complexes through the use of Cu2O. For abbreviations, please...
Scheme 21: Synthesis of abnormal-NHC–copper(I) complexes by Bertrand, Cazin and co-workers [35].
Scheme 22: Microwave-assisted synthesis of thiazolylidene/benzothiazolylidene–CuBr complexes by Bansal and co-...
Scheme 23: Synthesis of NHC–CuX complexes through transmetallation.
Scheme 24: Preparation of six- or seven-membered NHC–Cu(I) complexes through transmetalation from Ag(I) comple...
Scheme 25: Synthesis of 1,2,3-triazolylidene–CuCl complexes through transmetallation of Ag(I) complexes genera...
Scheme 26: Synthesis of NHC–copper complexes having both Cu(I) and Cu(II) units through transmetalation report...
Scheme 27: Synthesis of new [(IPr(CH2)3Si(OiPr)3)CuX] complexes and anchoring on MCM-41.
Scheme 28: Synthesis of bis(trimethylsilyl)phosphide–Cu(I)–NHC complexes through ligand displacement.
Scheme 29: Synthesis of silyl- and stannyl [(NHC)Cu−ER3] complexes.
Scheme 30: Synthesis of amido-, phenolato-, thiophenolato–Cu(NHC) complexes.
Scheme 31: Synthesis of first isolable NHC–Cu–difluoromethyl complexes reported by Sanford et al. [44].
Scheme 32: Synthesis of NHC–Cu(I)–bifluoride complexes reported by Riant, Leyssens and co-workers [45].
Scheme 33: Conjugate addition of Et2Zn to enones catalyzed by an NHC–Cu(I) complex reported by Woodward in 200...
Scheme 34: Hydrosilylation of a carbonyl group.
Scheme 35: NHC–Cu(I)-catalyzed hydrosilylation of ketones reported by Nolan et al. [48,49].
Scheme 36: Application of chiral NHC–CuCl complex 104 for the enantioselective hydrosilylation of ketones.
Scheme 37: Hydrosilylation reactions catalyzed by NHC–Cu(Ot-Bu) complexes.
Scheme 38: NHC–CuCl catalyzed carbonylative silylation of alkyl halides.
Scheme 39: Nucleophilic conjugate addition to an activated C=C bond.
Figure 6: Molecular electrostatic potential maps (MESP) of two NHC–CuX complexes computed at the B3LYP/def2-S...
Scheme 40: Conjugate addition of Grignard reagents to 3-alkyl-substituted cyclohexenones catalyzed by a chiral...
Scheme 41: NHC–copper complex-catalyzed conjugate addition of Grignard reagent to 3-substituted hexenone repor...
Scheme 42: Conjugate addition or organoaluminum reagents to β-substituted cyclic enones.
Scheme 43: Conjugate addition of boronates to acyclic α,β-unsaturated carboxylic esters, ketones, and thioeste...
Scheme 44: NHC–Cu(I)-catalyzed hydroboration of an allene reported by Hoveyda [63].
Scheme 45: Conjugate addition of Et2Zn to cyclohexenone catalyzed by NHC–Cu(I) complex derived from benzimidaz...
Scheme 46: Asymmetric conjugate addition of diethylzinc to 3-nonen-2-one catalyzed by NHC–Cu complexes derived...
Scheme 47: General scheme of a [3 + 2] cycloaddition reaction.
Scheme 48: [3 + 2] Cycloaddition of azides with alkynes catalyzed by NHC–Cu(I) complexes reported by Diez-Gonz...
Scheme 49: Application of NHC–CuCl/N-donor combination to catalyze the [3 + 2] cycloaddition of benzyl azide w...
Scheme 50: [3 + 2] Cycloaddition of azides with acetylenes catalyzed by bis(NHC)–Cu complex 131 and mixed NHC–...
Figure 7: NHC–CuCl complex 133 as catalyst for the [3 + 2] cycloaddition of alkynes with azides at room tempe...
Scheme 51: [3 + 2] Cycloaddition of a bulky azide with an alkynylpyridine using [(NHC)Cu(μ-I)2Cu(NHC)] copper ...
Scheme 52: [3 + 2] Cycloaddition of benzyl azide with phenylacetylene under homogeneous and heterogeneous cata...
Scheme 53: [3 + 2] Cycloaddition of benzyl azide with acetylenes catalyzed by bisthiazolylidene dicopper(I) co...
Figure 8: Copper (I)–NHC linear coordination polymer 137 and its conversion into tetranuclear (138) and dinuc...
Scheme 54: An A3 reaction.
Scheme 55: Synthesis of SiO2-immobilized NHC–Cu(I) catalyst 141 and its application in the A3-coupling reactio...
Scheme 56: Preparation of dual-purpose Ru@SiO2–[(NHC)CuCl] catalyst system 142 developed by Bordet, Leitner an...
Scheme 57: Application of the catalyst system Ru@SiO2–[Cu(NHC)] 142 to the one-pot tandem A3 reaction and hydr...
Scheme 58: A3 reaction of phenylacetylene with secondary amines and aldehydes catalyzed by benzothiazolylidene...
Figure 9: Kohn–Sham HOMOs of phenylacetylene and NHC–Cu(I)–phenylacetylene complex computed at the B3LYP/def2...
Figure 10: Energies of the FMOs of phenylacetylene, iminium ion, and NHC–Cu(I)–phenylacetylene complex compute...
Scheme 59: NHC–Cu(I) catalyzed diboration of ketones 147 by reacting with bis(pinacolato)diboron (148) reporte...
Scheme 60: Protoboration of terminal allenes catalyzed by NHC–Cu(I) complexes reported by Hoveyda and co-worke...
Scheme 61: NHC–CuCl-catalyzed borylation of α-alkoxyallenes to give 2-boryl-1,3-butadienes.
Scheme 62: Regioselective hydroborylation of propargylic alcohols and ethers catalyzed by NHC–CuCl complexes 1...
Scheme 63: NHC–CuOt-Bu-catalyzed semihydrogenation and hydroborylation of alkynes.
Scheme 64: Enantioselective NHC–Cu(I)-catalyzed hydroborations of 1,1-disubstituted aryl olefins reported by H...
Scheme 65: Enantioselective NHC–Cu(I)-catalyzed hydroboration of exocyclic 1,1-disubstituted alkenes reported ...
Scheme 66: Markovnikov-selective NHC–CuOH-catalyzed hydroboration of alkenes and alkynes reported by Jones et ...
Scheme 67: Dehydrogenative borylation and silylation of styrenes catalyzed by NHC–CuOt-Bu complexes developed ...
Scheme 68: N–H/C(sp2)–H carboxylation catalyzed by NHC–CuOH complexes.
Scheme 69: C–H Carboxylation of benzoxazole and benzothiazole derivatives with CO2 using a 1,2,3-triazol-5-yli...
Scheme 70: Use of Cu(I) complex derived from diethylene glycol-functionalized imidazo[1,5,a] pyridin-3-ylidene...
Scheme 71: Allylation and alkenylation of polyfluoroarenes and heteroarenes catalyzed by NHC–Cu(I) complexes r...
Scheme 72: Enantioselective C(sp2)–H allylation of (benz)oxazoles and benzothiazoles with γ,γ-disubstituted pr...
Scheme 73: C(sp2)–H arylation of arenes catalyzed by dual NHC–Cu/NHC–Pd catalytic system.
Scheme 74: C(sp2)–H Amidation of (hetero)arenes with N-chlorocarbamates/N-chloro-N-sodiocarbamates catalyzed b...
Scheme 75: NHC–CuI catalyzed thiolation of benzothiazoles and benzoxazoles.
Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91
Graphical Abstract
Scheme 1: Representative cascade reactions of Michael adducts of 3-methyleneoxindoles.
Figure 1: Crystal structure of dispiro compound 3a.
Figure 2: Crystal structure of compound 4a.
Scheme 2: Proposed reaction mechanism.
Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73
Graphical Abstract
Scheme 1: Various cycloaddition reactions of 5,6-unsymmetric 1,4-dihydropyridines.
Figure 1: Single crystal structure of the compound 4k.
Figure 2: Single crystal structure of compound 5a.
Figure 3: Single crystal structure of compound 6f.
Scheme 2: Plausible reaction mechanism for the various products 4, 5, and 6.
Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53
Graphical Abstract
Scheme 1: Diversity of structures synthesized by combining IMCR’s.
Figure 1: Drugs possessing imidazo[1,2-a]pyridine unit.
Figure 2: Drugs possessing peptide unit.
Scheme 2: Diversity of GBB reaction products as precursors for Ugi reaction.
Scheme 3: Synthesis of new acids containing a substituted imidazo[1,2-a]pyridine fragment.
Scheme 4: Synthesis of new peptidomimetics containing a substituted imidazo[1,2-a]pyridine fragment.
Scheme 5: Synthesis and reactivity of new acids containing a substituted imidazo[1,2-a]pyridine fragment with...
Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52
Graphical Abstract
Figure 1: Biologically active molecules containing α-arylglycine motifs (highlighted in green and blue).
Scheme 1: The Petasis reaction – fundamental reactivities and recent developments.
Scheme 2: Observations from previous studies and mechanistic rationale.
Scheme 3: Initial experiments.
Scheme 4: Reaction scope – aryltrifluoroborates (yields and enantiomeric ratios in parentheses refer to our p...
Scheme 5: Synthesis of both enantiomers of arylglycine building block 18.
Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22
Graphical Abstract
Figure 1: Representative drug molecules based on pyrazole, thioamide, and amide derivatives.
Figure 2: Previous and present findings for the synthesis of thioamide derivatives.
Scheme 1: Synthesis of pyrazole C-3-tethered thioamides.
Scheme 2: Synthesis of pyrazole C-4-tethered thioamides.
Scheme 3: Metal- and catalyst-free preparation of pyrazole C-5-linked thioamide conjugates.
Scheme 4: Synthesis of 4-iodopyrazole C-3-tethered thioamides.
Scheme 5: Gram-scale scope of the current protocol.
Scheme 6: Control experiment.
Scheme 7: H2O2-mediated synthesis of pyrazole-pyridine conjugates with amide tethers.
Scheme 8: Synthesis of pyrazole-pyridine conjugates 9F and 10F having amide tethers.
Scheme 9: A tentative mechanism for the formation of pyrazole conjugates with thioamide and amide linkage.
Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175
Graphical Abstract
Figure 1: (a) Previously developed three-component approach to 1,5-disubstituted 1,2,3-triazoles; (b) double ...
Scheme 1: Results of a trial reaction between 1, o-azidobenzaldehyde (3a) and propargylamine.
Figure 2: Diversely bioactive compounds based on scaffolds A and B.
Scheme 2: Three-component reaction of 1, propargylamine and various o-azidobenzaldehydes.
Figure 3: Aromatic azido aldehydes 3j–l that failed to react with 1 and propargylamine.
Scheme 3: Variations of the amine component in the reactions with 1 and 3a.
Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168
Graphical Abstract
Figure 1: Selected imidazole-based bioactive molecules.
Scheme 1: Formation of ethyl 2-cyano-2-(1,3-dihydro-2H-imidazole-2-ylidene)acetate derivatives via [3 + 2] cy...
Scheme 2: C–H/C–Li coupling reaction of 2H-imidazole 1-oxides with pentafluorophenyllithium.
Scheme 3: Transition-metal-free coupling reaction of 2H-imidazole 1-oxides with polyphenols. Reaction conditi...
Scheme 4: Halogenation reaction of 2-unsubstituted imidazole N-oxides using tosyl halogenides.
Scheme 5: Solvent-free chlorination reaction of imidazole N-oxides.
Scheme 6: Multicomponent reaction of imidazole N-oxides 28 with Meldrum’s acid (26) and aldehydes.
Scheme 7: Multicomponent reaction of imidazole N-oxides with CH-acids and aldehydes. Reaction conditions: aTh...
Scheme 8: Three-component condensation reaction of imidazole N-oxides, arylglyoxals, and CH-acids 38 (dimedon...
Scheme 9: Synthesis of imidazole-2-thiones containing cyclohexyl-substituents at 3-position.
Scheme 10: Preparation of optically active derivatives of 3-butoxyimidazole-2-thione.
Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118
Graphical Abstract
Figure 1: Structure of naturally occurring and synthetic 2-pyrrolidone derivatives.
Figure 2: Structure of natural compounds containing a 1,5-dihydro-2H-pyrrol-2-one subunit.
Scheme 1: Synthesis of substituted 4-acetyl-3-hydroxy-3-pyrroline-2-ones 4 via three-component reaction.
Scheme 2: Proposed mechanistic path for the synthesis of substituted 4-acetyl-3-hydroxy-3-pyrroline-2-ones.
Scheme 3: Tautomerism of compounds 4a–c in DMSO.
Figure 3: View of the molecular structure of compound 10aa with atom labeling. Displacement ellipsoids are dr...
Figure 4: The PES of reaction for the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-dione 10ab enamine de...
Scheme 4: Reaction pathways from 4a, 4a’ to 10ab via IS5 in the gase phase.
Scheme 5: Reaction pathways from 4a to 10ab-v2 via IS3 in the gase phase.
Figure 5: The PES for the possible pathways (1), (2), (3), and (4) in ethanol solvent.
Figure 6: The optimized structures of some reactants, intermediates, transition states, and products in the p...
Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99
Graphical Abstract
Scheme 1: Representative cycloaddition reactions of phenacylmalononitriles.
Figure 1: Single crystal structure of compound 3k.
Figure 2: Single crystal structure of compound 4a.
Figure 3: Single crystal structure of compound 4c.
Scheme 2: Proposed reaction mechanism for compounds 3, 4, and 5.
Figure 4: Single crystal structure of compound 5.
Scheme 3: Control experiment.
Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87
Graphical Abstract
Figure 1: Biologically active selenides having alkynyl or imidazopyridinyl groups.
Figure 2: (a) ORTEP drawing of 4aa and (b) its stacking structure.
Scheme 1: Control reactions.
Figure 3: Proposed mechanism.
Scheme 2: Transformation from 4aa.
Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80
Graphical Abstract
Scheme 1: Construction of diverse tetrahydrocarbazoles via Levy-type reaction.
Scheme 2: Synthesis of spiro[carbazole-3,3'-inolines]. Reaction conditions: 2-methylindole (0.5 mmol), aromat...
Scheme 3: Synthesis of spiro[carbazole-2,3'-indolines]. Reaction conditions: 2-methylindole (0.5 mmol), aroma...
Scheme 4: Synthesis of tetrahydrospiro[carbazole-3,5'-pyrimidines]. Reaction conditions: 2-methylindole (0.5 ...
Scheme 5: Synthesis of tetrahydrospiro[carbazole-3,1'-cycloalkane]-diones. Reaction conditions: 2-methylindol...
Scheme 6: Synthesis of 3,3'-(arylmethylene)bis(2-methyl-1H-indole). Reaction conditions: 2-methylindole (1.0 ...
Scheme 7: Proposed reaction mechanism for the multicomponent reaction.
Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70
Graphical Abstract
Figure 1: Inductive heating, a powerful tool in industry and the Life Sciences.
Figure 2: Electric displacement field of a ferromagnetic and superparamagnetic material.
Figure 3: Temperature profiles of reactors heated conventionally and by RF heating (Figure 3 redrawn from [24]).
Scheme 1: Continuous flow synthesis of isopulegol (2) from citronellal (1).
Scheme 2: Dry (reaction 1) and steam (reaction 2) methane reforming.
Scheme 3: Calcination and RF heating.
Scheme 4: The continuously operated “Sabatier” process.
Scheme 5: Biofuel production from biomass using inductive heating for pyrolysis.
Scheme 6: Water electrolysis using an inductively heated electrolysis cell.
Scheme 7: Dimroth rearrangement (reaction 1) and three-component reaction (reaction 2) to propargyl amines 8 ...
Figure 4: A. Flow reactor filled with magnetic nanostructured particles (MagSilicaTM) and packed bed reactor ...
Scheme 8: Claisen rearrangement in flow: A. comparison between conventional heating (external oil bath), micr...
Scheme 9: Continuous flow reactions and comparison with batch reaction (oil bath). A. Pd-catalyzed transfer h...
Scheme 10: Continuous flow reactions and comparison with batch reaction (oil bath). A. pericyclic reactions an...
Scheme 11: Reactions under flow conditions using inductively heated fixed-bed materials serving as stoichiomet...
Scheme 12: Reactions under flow conditions using inductively heated fixed-bed materials serving as catalysts: ...
Scheme 13: Two step flow protocol for the preparation of 1,1'-diarylalkanes 77 from ketones and aldehydes 74, ...
Scheme 14: O-Alkylation, the last step in the multistep flow synthesis of Iloperidone (80) accompanied with a ...
Scheme 15: Continuous two-step flow process consisting of Grignard reaction followed by water elimination bein...
Scheme 16: Inductively heated continuous flow protocol for the synthesis of Iso E Super (88) [91,92].
Scheme 17: Three-step continuous flow synthesis of macrocycles 89 and 90 with musk-like olfactoric properties.
Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3
Graphical Abstract
Figure 1: Selected examples of natural products and drugs possessing the indane scaffold.
Scheme 1: Known strategies and conceptual advance of this contribution.
Figure 2: Selected examples of bioactive spirobarbiturates.
Figure 3: The screened organocatalysts.
Scheme 2: Substrate scope of 2-isothiocyanato-1-indanones. The reactions were carried out with 1 (0.12 mmol), ...
Scheme 3: Substrate scope of barbiturate-based olefins. The reactions were carried out with 1a (0.12 mmol), 2...
Figure 4: X-ray crystal structure of 3ae (displacement ellipsoids are drawn at the 50% probability level).
Scheme 4: Gram-scale synthesis of 3ah.
Scheme 5: Further transformation of 3ah.
Scheme 6: One-pot three-component reaction.
Scheme 7: Proposed reaction mechanism.
Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168
Graphical Abstract
Figure 1: Natural isopavine alkaloids and synthetic derivatives of isopavine.
Figure 2: The structure and numbering of dihydromethanodibenzoazocine.
Scheme 1: The Petasis reaction and the Pomeranz–Fritsch–Bobbitt cyclization.
Scheme 2: The synthesis of 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids via a combination ...
Scheme 3: Synthesis of N-benzylated aminoacetaldehyde acetals 3a–e. Conditions: a) reaction run in EtOH; b) r...
Scheme 4: Synthesis of amino acids 6a–g.
Scheme 5: Synthesis of dihydromethanodibenzoazocine-5-carboxylic acids 7a–f. Conditions: a) 20% HCl, rt, 24 h...
Scheme 6: Synthesis of TA-073.
Scheme 7: Reaction of 6a with 4% aqueous HCl solution in THF and with 20% aqueous HCl solution. Conditions: a...
Scheme 8: Three pathways of the synthesis of 12, the decarboxylated analogue of 6a.
Scheme 9: The chemical behavior of 12 in 4% aqueous HCl solution in THF and in 20% aqueous HCl solution.
Scheme 10: A plausible mechanism of the reaction of 6a with 4% aqueous HCl solution in THF.
Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143
Graphical Abstract
Scheme 1: Nickel-catalyzed cross-coupling versus C‒H activation.
Figure 1: Oxidative and reductive quenching cycles of a photocatalyst. [PC] = photocatalyst, A = acceptor, D ...
Scheme 2: Photoredox nickel-catalyzed C(sp3)–H arylation of dimethylaniline (1a).
Scheme 3: Photoredox nickel-catalyzed arylation of α-amino, α-oxy and benzylic C(sp3)‒H bonds with aryl bromi...
Figure 2: Proposed catalytic cycle for the photoredox-mediated HAT and nickel catalysis enabled C(sp3)‒H aryl...
Scheme 4: Photoredox arylation of α-amino C(sp3)‒H bonds with aryl iodides.
Figure 3: Proposed mechanism for photoredox nickel-catalyzed α-amino C‒H arylation with aryl iodides.
Scheme 5: Nickel-catalyzed α-oxy C(sp3)−H arylation of cyclic and acyclic ethers.
Figure 4: Proposed catalytic cycle for the C(sp3)−H arylation of cyclic and acyclic ethers.
Scheme 6: Photochemical nickel-catalyzed C–H arylation of ethers.
Figure 5: Proposed catalytic cycle for the nickel-catalyzed arylation of ethers with aryl bromides.
Scheme 7: Nickel-catalyzed α-amino C(sp3)‒H arylation with aryl tosylates.
Scheme 8: Arylation of α-amino C(sp3)‒H bonds by in situ generated aryl tosylates from phenols.
Scheme 9: Formylation of aryl chlorides through redox-neutral 2-functionalization of 1,3-dioxolane (13).
Scheme 10: Photochemical C(sp3)–H arylation via a dual polyoxometalate HAT and nickel catalytic manifold.
Figure 6: Proposed mechanism for C(sp3)–H arylation through dual polyoxometalate HAT and nickel catalytic man...
Scheme 11: Photochemical nickel-catalyzed α-hydroxy C‒H arylation.
Scheme 12: Photochemical synthesis of fluoxetine (21).
Scheme 13: Photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl bromides.
Figure 7: Proposed mechanism for the photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl brom...
Scheme 14: Photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and nickel catalysis.
Figure 8: Proposed mechanism for photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and ...
Scheme 15: Benzophenone- and nickel-catalyzed photoredox benzylic C–H arylation.
Scheme 16: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)–H arylation.
Scheme 17: Photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Figure 9: Proposed mechanism for the photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Scheme 18: Photoredox nickel-catalyzed α-(sp3)‒H arylation of secondary benzamides with aryl bromides.
Scheme 19: Enantioselective sp3 α-arylation of benzamides.
Scheme 20: Nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxalates.
Figure 10: Proposed mechanism for the nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxal...
Scheme 21: C(sp3)−H arylation of bioactive molecules using mpg-CN photocatalysis and nickel catalysis.
Figure 11: Proposed mechanism for the mpg-CN/nickel photocatalytic C(sp3)–H arylation.
Scheme 22: Nickel-catalyzed synthesis of 1,1-diarylalkanes from alkyl bromides and aryl bromides.
Figure 12: Proposed mechanism for photoredox nickel-catalyzed C(sp3)–H alkylation via polarity-matched HAT.
Scheme 23: Photoredox nickel-catalyzed C(sp3)‒H alkylation via polarity-matched HAT.
Scheme 24: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of ethers.
Scheme 25: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of amides and thioethers.
Scheme 26: Photoredox and nickel-catalyzed C(sp3)‒H alkylation of benzamides with alkyl bromides.
Scheme 27: CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers with alkyl bromides.
Figure 13: Proposed mechanism for the CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers.
Scheme 28: Nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides and acid chlorides using trimethy...
Figure 14: Proposed catalytic cycle for the nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides ...
Scheme 29: Photochemical nickel-catalyzed C(sp3)–H methylations.
Scheme 30: Photoredox nickel catalysis-enabled alkylation of unactivated C(sp3)–H bonds with alkyl bromides.
Scheme 31: Photochemical C(sp3)–H alkenylation with alkenyl tosylates.
Scheme 32: Photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Figure 15: Proposed mechanism for the photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Scheme 33: Photoredox nickel-catalyzed hydroalkylation of activated alkynes with C(sp3)−H bonds.
Scheme 34: Allylation of unactivated C(sp3)−H bonds with allylic chlorides.
Scheme 35: Photochemical nickel-catalyzed α-amino C(sp3)–H allylation of secondary amides with trifluoromethyl...
Scheme 36: Photoredox δ C(sp3)‒H allylation of secondary amides with trifluoromethylated alkenes.
Scheme 37: Photoredox nickel-catalyzed acylation of α-amino C(sp3)‒H bonds of N-arylamines.
Figure 16: Proposed mechanism for the photoredox nickel-catalyzed acylation of α-amino C(sp3)–H bonds of N-ary...
Scheme 38: Photocatalytic α‑acylation of ethers with acid chlorides.
Figure 17: Proposed mechanism for the photocatalytic α‑acylation of ethers with acid chlorides.
Scheme 39: Photoredox and nickel-catalyzed C(sp3)‒H esterification with chloroformates.
Scheme 40: Photoredox nickel-catalyzed dehydrogenative coupling of benzylic and aldehydic C–H bonds.
Figure 18: Proposed reaction pathway for the photoredox nickel-catalyzed dehydrogenative coupling of benzylic ...
Scheme 41: Photoredox nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic ac...
Scheme 42: Nickel-catalyzed C(sp3)‒H acylation with N-acylsuccinimides.
Figure 19: Proposed mechanism for the nickel-catalyzed C(sp3)–H acylation with N-acylsuccinimides.
Scheme 43: Nickel-catalyzed benzylic C–H functionalization with acid chlorides 45.
Scheme 44: Photoredox nickel-catalyzed benzylic C–H acylation with N-acylsuccinimides 84.
Scheme 45: Photoredox nickel-catalyzed acylation of indoles 86 with α-oxoacids 87.
Scheme 46: Nickel-catalyzed aldehyde C–H functionalization.
Figure 20: Proposed catalytic cycle for the photoredox nickel-catalyzed aldehyde C–H functionalization.
Scheme 47: Photoredox carboxylation of methylbenzenes with CO2.
Figure 21: Proposed mechanism for the photoredox carboxylation of methylbenzenes with CO2.
Scheme 48: Decatungstate photo-HAT and nickel catalysis enabled alkene difunctionalization.
Figure 22: Proposed catalytic cycle for the decatungstate photo-HAT and nickel catalysis enabled alkene difunc...
Scheme 49: Diaryl ketone HAT catalysis and nickel catalysis enabled dicarbofunctionalization of alkenes.
Figure 23: Proposed catalytic mechanism for the diaryl ketone HAT catalysis and nickel catalysis enabled dicar...
Scheme 50: Overview of photoredox nickel-catalyzed C–H functionalizations.
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93
Graphical Abstract
Figure 1: Icilio Guareschi (1847–1918). (Source: Annali della Reale Accademia di Agricoltura di Torino 1919, ...
Scheme 1: Vitamin B6 (pyridoxine, 1), gabapentin (2), and thymol (3).
Figure 2: Baliatico (Nursing) by Francesco Scaramuzza (275 cm × 214 cm, Parma, Complesso Museale della Pilott...
Figure 3: Schiff’s fictitious report on the foundation of the Gazzetta Chimica Italiana (Image reproduced fro...
Scheme 2: Reaction of thymol (3) with chloroform under the basic conditions of the Guareschi–Lustgarten react...
Figure 4: The chemistry building of Turin University in a historical picture. Note, that one of the “mysterio...
Scheme 3: Triacetonamine (6) and the related compounds phorone (7), α-eucaine (8), and tropinone (9).
Scheme 4: Taxonomy of the Guareschi pyridone syntheses.
Scheme 5: The catalytic cycle of the “1897 reaction”.
Scheme 6: Resonance forms of the radical 10.
Figure 5: The wet chamber used by Guareschi to restore parchments (Gorrini, G. L'incendio della R. Biblioteca...
Figure 6: The Guareschi mask. (Servizio Chimico Militare. L'opera di Icilio Guareschi precursore della masche...
Figure 7: Guareschi’s bust at the Dipartimento di Scienza e Tecnologia del Farmaco of Turin University. Permi...
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67
Graphical Abstract
Scheme 1: The electron transfer process in EDA complexes.
Scheme 2: Synthesis of benzo[b]phosphorus oxide 3 initiated by an EDA complex.
Scheme 3: Mechanism of the synthesis of quinoxaline derivative 7.
Scheme 4: Synthesis of imidazole derivative 10 initiated by an EDA complex.
Scheme 5: Synthesis of sulfamoylation product 12 initiated by an EDA complex.
Scheme 6: Mechanism of the synthesis of sulfamoylation product 12.
Scheme 7: Synthesis of indole derivative 22 initiated by an EDA complex.
Scheme 8: Synthesis of perfluoroalkylated pyrimidines 26 initiated by an EDA complex.
Scheme 9: Synthesis of phenanthridine derivative 29 initiated by an EDA complex.
Scheme 10: Synthesis of cis-tetrahydroquinoline derivative 32 initiated by an EDA complex.
Scheme 11: Mechanism of the synthesis of cis-tetrahydroquinoline derivative 32.
Scheme 12: Synthesis of phenanthridine derivative 38 initiated by an EDA complex.
Scheme 13: Synthesis of spiropyrroline derivative 40 initiated by an EDA complex.
Scheme 14: Synthesis of benzothiazole derivative 43 initiated by an EDA complex.
Scheme 15: Synthesis of perfluoroalkyl-s-triazine derivative 45 initiated by an EDA complex.
Scheme 16: Synthesis of indoline derivative 47 initiated by an EDA complex.
Scheme 17: Mechanism of the synthesis of spirocyclic indoline derivative 47.
Scheme 18: Synthesis of cyclobutane product 50 initiated by an EDA complex.
Scheme 19: Mechanism of the synthesis of spirocyclic indoline derivative 50.
Scheme 20: Synthesis of 1,3-oxazolidine compound 59 initiated by an EDA complex.
Scheme 21: Synthesis of trifluoromethylated product 61 initiated by an EDA complex.
Scheme 22: Synthesis of indole alkylation product 64 initiated by an EDA complex.
Scheme 23: Synthesis of perfluoroalkylation product 67 initiated by an EDA complex.
Scheme 24: Synthesis of hydrotrifluoromethylated product 70 initiated by an EDA complex.
Scheme 25: Synthesis of β-trifluoromethylated alkyne product 71 initiated by an EDA complex.
Scheme 26: Mechanism of the synthesis of 2-phenylthiophene derivative 74.
Scheme 27: Synthesis of allylated product 80 initiated by an EDA complex.
Scheme 28: Synthesis of trifluoromethyl-substituted alkynyl product 84 initiated by an EDA complex.
Scheme 29: Synthesis of dearomatized fluoroalkylation product 86 initiated by an EDA complex.
Scheme 30: Mechanism of the synthesis of dearomatized fluoroalkylation product 86.
Scheme 31: Synthesis of C(sp3)–H allylation product 91 initiated by an EDA complex.
Scheme 32: Synthesis of perfluoroalkylation product 93 initiated by an EDA complex.
Scheme 33: Synthesis of spirocyclic indolene derivative 95 initiated by an EDA complex.
Scheme 34: Synthesis of perfluoroalkylation product 97 initiated by an EDA complex.
Scheme 35: Synthesis of alkylated indole derivative 100 initiated by an EDA complex.
Scheme 36: Mechanism of the synthesis of alkylated indole derivative 100.
Scheme 37: Synthesis of arylated oxidized indole derivative 108 initiated by an EDA complex.
Scheme 38: Synthesis of 4-ketoaldehyde derivative 111 initiated by an EDA complex.
Scheme 39: Mechanism of the synthesis of 4-ketoaldehyde derivative 111.
Scheme 40: Synthesis of perfluoroalkylated olefin 118 initiated by an EDA complex.
Scheme 41: Synthesis of alkylation product 121 initiated by an EDA complex.
Scheme 42: Synthesis of acylation product 123 initiated by an EDA complex.
Scheme 43: Mechanism of the synthesis of acylation product 123.
Scheme 44: Synthesis of trifluoromethylation product 126 initiated by an EDA complex.
Scheme 45: Synthesis of unnatural α-amino acid 129 initiated by an EDA complex.
Scheme 46: Synthesis of thioether derivative 132 initiated by an EDA complex.
Scheme 47: Synthesis of S-aryl dithiocarbamate product 135 initiated by an EDA complex.
Scheme 48: Mechanism of the synthesis of S-aryl dithiocarbamate product 135.
Scheme 49: Synthesis of thioether product 141 initiated by an EDA complex.
Scheme 50: Mechanism of the synthesis of borate product 144.
Scheme 51: Synthesis of boronation product 148 initiated by an EDA complex.
Scheme 52: Synthesis of boration product 151 initiated by an EDA complex.
Scheme 53: Synthesis of boronic acid ester derivative 154 initiated by an EDA complex.
Scheme 54: Synthesis of β-azide product 157 initiated by an EDA complex.
Scheme 55: Decarboxylation reaction initiated by an EDA complex.
Scheme 56: Synthesis of amidated product 162 initiated by an EDA complex.
Scheme 57: Synthesis of diethyl phenylphosphonate 165 initiated by an EDA complex.
Scheme 58: Mechanism of the synthesis of diethyl phenylphosphonate derivative 165.
Scheme 59: Synthesis of (Z)-2-iodovinyl phenyl ether 168 initiated by an EDA complex.
Scheme 60: Mechanism of the synthesis of (Z)-2-iodovinyl phenyl ether derivative 168.
Scheme 61: Dehalogenation reaction initiated by an EDA complex.
Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258
Graphical Abstract
Scheme 1: Metal-catalyzed difunctionalization of unsaturated carbon–carbon bonds.
Scheme 2: Substrate scope for the synthesis of the β-fluorovinylphosphonates 2 using diethyl phosphite. React...
Scheme 3: Substrate scope for the synthesis of the β-fluorovinylphosphonates 3 using dimethyl phosphite. Reac...
Scheme 4: Radical-trapping experiments.
Scheme 5: Proposed mechanism for the silver-catalyzed phosphonofluorination of alkynes.
Scheme 6: Attempted use of a suspected phosphonofluorination intermediate to synthesize a β-fluorovinylphosph...
Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241
Graphical Abstract
Figure 1: Representative biologically active N-(hetero)aryl-4,5-unsubstituted pyrrole scaffolds.
Scheme 1: Typical routes to N-(heteroaryl)-4,5-unsubstituted pyrroles.
Scheme 2: Substrate scope of the pyrrole synthesis.
Scheme 3: Synthesis of N-heterocyclic pyrroles.
Scheme 4: Direct synthesis of pyrrole-3-carboxamide derivatives.
Scheme 5: Plausible mechanism of the three-component reaction.
Scheme 6: Synthesis of polysubstituted pyrazolo[3,4-b]pyridine derivatives.
Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238
Graphical Abstract
Figure 1: Schematic illustration for the preparation of the catalyst in this work.
Figure 2: FTIR spectra of LS, LS-FAS, and LS-FAS-Cu.
Figure 3: Thermogravimetric weight loss of the obtained materials LS-FAS and LS-FAS-Cu.
Figure 4: FSEM imagine of LS-FAS-Cu in different scale label a) 1 μm, b) 200 nm; FTEM images of LS-FAS-Cu in ...
Figure 5: XPS spectra of LS-FAS-Cu in the regions of C 1s, O 1s, Cu 2p3/2 and Cu LMM (inset).
Scheme 1: Substrate scope of LS-FAS-Cu catalyzed three-component reactions of 4-aminoindoles, alkynes and ald...
Figure 6: Recyclability of LS-FAS-Cu, LS-FM-Cu and Resin-Cu in the reaction between compounds 1a, 2a and 3a.
Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163
Graphical Abstract
Scheme 1: Post-transformations of 2-oxo-aldehyde-derived Ugi adducts 8.
Scheme 2: Synthesis of 2-oxo-aldehyde-derived Ugi adducts.
Figure 1: Molecular representation of the X-ray crystal structure of (S)-12e (slow enantiomer).