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Search for "multicomponent coupling reaction" in Full Text gives 7 result(s) in Beilstein Journal of Organic Chemistry.
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
- ) [131]. In addition, a gram scale operation has been successfully demonstrated. In addition, Hu and co-workers (2020) studied a catalyst-free multicomponent coupling reaction of benzynes derived from alkyne 349, cyclopropenone 309, and sulfoxides to give the corresponding o-(methylthio)phenyl acrylates
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.
Combination of multicomponent KA2 and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones
- Riccardo Innocenti,
- Elena Lenci,
- Gloria Menchi and
- Andrea Trabocchi
Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23
- . Following our interest to DOS as a synthetic strategy for the generation of molecular scaffolds according to a couple/pair approach [45][46][47], we reasoned to combine the copper-catalyzed ketone–amine–alkyne (KA2) multicomponent coupling reaction [48] with the Pauson–Khand cycloaddition as the pairing
- components in the outcome of the multicomponent coupling reaction. Similarly, the use of piperidone as the ketone component proved to work only when the amino group was protected as Boc, whereas the N-methyl derivative did not proceed to the coupling product (Table 1, entries 10 and 9, respectively). Indeed
Graphical Abstract
Figure 1: Chemical structure of representative approved drugs containing a spirocyclic moiety.
Scheme 1: Synthetic strategies for accessing pyrrolocyclopentenone derivatives, including the novel couple/pa...
Scheme 2: Couple/pair approach using combined KA2 and Pauson–Khand multicomponent reactions.
Scheme 3: Follow-up chemistry on compound 5 taking advantage of the enone chemistry. Reaction conditions. (i)...
Figure 2: Top: Selected NOE contacts from NOESY 1D spectra of compound 36; bottom: low energy conformer of 36...
Figure 3: PCA plot resulting from the correlation between PC1 vs PC2, showing the positioning in the chemical...
Figure 4: PMI plot showing the skeletal diversity of compounds 3–39 (blue diamonds) with respect to the refer...
Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst
- Kimihiro Komeyama,
- Shunsuke Sakiyama,
- Kento Iwashita,
- Itaru Osaka and
- Ken Takaki
Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118
- substituted secondary alcohols, as demonstrated in the Nozaki–Hiyama–Kishi (NHK) reaction (Scheme 2) [4][5][6][7][8][9]. Although the catalyst combination allows the use of organic halides as carbon nucleophiles, a multicomponent coupling reaction using a similar catalyst combination has had limited success
Graphical Abstract
Scheme 1: Nucleophilic and π-electrophilic characters of organometallics depending on the central metals.
Scheme 2: Ni/Cr or Co/Cr-catalyzed NHK reaction.
Scheme 3: Functionalization of alkynes via carbocobaltation.
Scheme 4: Cyclization/borylation of alkynyl iodoarenes using the Co/Cr catalyst.
Scheme 5: Three-component coupling of aryl iodides, arenes, and aldehydes using Co/Cr catalyst (this work).
Scheme 6: Screening of aldehydes in the Co/Cr-catalyzed three-component coupling reaction. All yields are det...
Scheme 7: Screening of aryl iodides in the Co/Cr-catalyzed three-component coupling reaction. All yields are ...
Scheme 8: Screening of allenes in the Co/Cr-catalyzed three-component coupling reaction. All yields are deter...
Scheme 9: Reversed diastereoselectivity using allenyl ethers 5 and 6. a4-chlorobenzaldehyde was used instead ...
Scheme 10: Stoichiometric reaction of phenylchromium(II or III) reagents (reaction 1) and the three-component ...
Scheme 11: The origin of the diastereoselectivity in the present three-component coupling.
Scheme 12: Plausible reaction mechanism of the three-component coupling.
Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence
- Amarendar Reddy Maddirala and
- Peter R. Andreana
Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74
- carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles. Keywords: convertible isocyanides; lactams; molecular diversity; oxindoles; transamidation; Introduction The Ugi-multicomponent coupling reaction [1][2], followed by post-modification
Graphical Abstract
Scheme 1: Previously reported post-Ugi-4CR methods for the synthesis of 2-oxindoles and spirocyclic 2-oxindol...
Scheme 2: Post-Ugi-4CR/transamidation/cyclization sequence.
Scheme 3: Base-promoted intramolecular 5-endo-dig cyclization.
Figure 1: ORTEP diagram of compound 7a.
Figure 2: Readily and synthetically accessible starting materials.
Scheme 4: Reaction scope with varying combinations of substrates.
Scheme 5: Synthesis of 5-chloro-1'-phenylspiro[indoline-3,2'-pyrrolidine]-2,5'-dione (8a).
Figure 3: Small molecule library of spiro[indoline-3,2'-pyrrolidine]-2,5'-dione analogs.
Scheme 6: Method applicability for the one-pot synthesis of 5-HT6 receptor antagonist 8j [53].
Application of heterocyclic aldehydes as components in Ugi–Smiles couplings
- Katelynn M. Mason,
- Michael S. Meyers,
- Abbie M. Fox and
- Sarah B. Luesse
Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191
- also a competent component for Ugi–Smiles adduct formation. Keywords: Diels–Alder cycloaddition; epoxyisoindoline; multicomponent coupling reaction; tandem reaction; Ugi–Smiles coupling; Introduction Synthetic methods to efficiently prepare libraries of biologically-relevant compounds are in demand
Graphical Abstract
Scheme 1: N-Arylepoxyisoindolines via tandem Ugi–Smiles/IMDA reaction.
Scheme 2: Reaction monitoring by 1H NMR for production of 1b.
Scheme 3: Use of a thienyl-substituted aldehyde for Ugi–Smiles couplings.
Silver and gold-catalyzed multicomponent reactions
- Giorgio Abbiati and
- Elisabetta Rossi
Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46
- ions, generated from the condensation of amines and aldehydes, represents the most convenient method to access propargylamines [4]. Although numerous examples of the A3-coupling reaction have been reported, there are still many challenges and opportunities for this multicomponent coupling reaction. The
Graphical Abstract
Scheme 1: General reaction mechanism for Ag(I)-catalyzed A3-coupling reactions.
Scheme 2: A3-coupling reaction catalyzed by polystyrene-supported NHC–silver halides.
Figure 1: Various NHC–Ag(I) complexes used as catalysts for A3-coupling.
Scheme 3: Proposed reaction mechanism for NHC–AgCl catalyzed A3-coupling reactions.
Scheme 4: Liu’s synthesis of pyrrole-2-carboxaldehydes 4.
Scheme 5: Proposed reaction mechanism for Liu’s synthesis of pyrrole-2-carboxaldehydes 4.
Scheme 6: Gold-catalyzed synthesis of propargylamines 1.
Scheme 7: A3-coupling catalyzed by phosphinamidic Au(III) metallacycle 6.
Scheme 8: Gold-catalyzed KA2-coupling.
Scheme 9: A3-coupling applied to aldehyde-containing oligosaccharides 8.
Scheme 10: A3-MCR for the preparation of propargylamine-substituted indoles 9.
Scheme 11: A3-coupling interceded synthesis of furans 12.
Scheme 12: A3/KA2-coupling mediated synthesis of functionalized dihydropyrazoles 13 and polycyclic dihydropyra...
Scheme 13: Au(I)-catalyzed entry to cyclic carbamimidates 17 via an A3-coupling-type approach.
Scheme 14: Proposed reaction mechanism for the Au(I)-catalyzed synthesis of cyclic carbamimidates 17.
Figure 2: Chiral trans-1-diphenylphosphino-2-aminocyclohexane–Au(I) complex 20.
Scheme 15: A3-coupling-type synthesis of oxazoles 21 catalyzed by Au(III)–salen complex.
Scheme 16: Proposed reaction mechanism for the synthesis of oxazoles 21.
Scheme 17: Synthesis of propargyl ethyl ethers 24 by an A3-coupling-type reaction.
Scheme 18: General mechanism of Ag(I)-catalyzed MCRs of 2-alkynylbenzaldehydes, amines and nucleophiles.
Scheme 19: General synthetic pathway to 1,3-disubstituted-1,2-dihydroisoquinolines.
Scheme 20: Synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 29.
Scheme 21: Synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 35 and 36.
Scheme 22: Rh(II)/Ag(I) co-catalyzed synthesis of 1,3-disubstituted-1,2-dihydroisoquinolines 40.
Scheme 23: General synthetic pathway to 2-amino-1,2-dihydroquinolines.
Scheme 24: Synthesis of 2-amino-1,2-dihydroquinolines 47.
Scheme 25: Synthesis of tricyclic H-pyrazolo[5,1-a]isoquinoline 48.
Scheme 26: Synthesis of tricyclic H-pyrazolo[5,1-a]isoquinolines 48.
Scheme 27: Cu(II)/Ag(I) catalyzed synthesis of H-pyrazolo[5,1-a]isoquinolines 48.
Scheme 28: Synthesis of 2-aminopyrazolo[5,1-a]isoquinolines 53.
Scheme 29: Synthesis of 1-(isoquinolin-1-yl)guanidines 55.
Scheme 30: Ag(I)/Cu(I) catalyzed synthesis of 2-amino-H-pyrazolo[5,1-a]isoquinolines 58.
Scheme 31: Ag(I)/Ni(II) co-catalyzed synthesis of 3,4-dihydro-1H-pyridazino[6,1-a]isoquinoline-1,1-dicarboxyla...
Scheme 32: Ag(I) promoted activation of the α-carbon atom of the isocyanide group.
Scheme 33: Synthesis of dihydroimidazoles 65.
Scheme 34: Synthesis of oxazoles 68.
Scheme 35: Stereoselective synthesis of chiral butenolides 71.
Scheme 36: Proposed reaction mechanism for the synthesis of butenolides 71.
Scheme 37: Stereoselective three-component approach to pirrolidines 77 by means of a chiral auxiliary.
Scheme 38: Stereoselective three-component approach to pyrrolidines 81 and 82 by means of a chiral catalyst.
Scheme 39: Synthesis of substituted five-membered carbocyles 86.
Scheme 40: Synthesis of regioisomeric arylnaphthalene lactones.
Scheme 41: Enantioselective synthesis of spiroacetals 96 by Fañanás and Rodríguez [105].
Scheme 42: Enantioselective synthesis of spiroacetals 101 by Gong [106].
Scheme 43: Synthesis of polyfunctionalized fused bicyclic ketals 103 and bridged tricyclic ketals 104.
Scheme 44: Proposed reaction mechanism for the synthesis of ketals 103 and 104.
Scheme 45: Synthesis of β-alkoxyketones 108.
Scheme 46: Synthesis of N-methyl-1,4-dihydropyridines 112.
Scheme 47: Synthesis of tetrahydrocarbazoles 115–117.
Scheme 48: Plausible reaction mechanism for the synthesis of tetrahydrocarbazoles 115–117.
Scheme 49: Carboamination, carboalkoxylation and carbolactonization of terminal alkenes.
Scheme 50: Oxyarylation of alkenes with arylboronic acids and Selectfluor as reoxidant.
Scheme 51: Proposed reaction mechanism for oxyarylation of alkenes.
Scheme 52: Oxyarylation of alkenes with arylsilanes and Selectfluor as reoxidant.
Scheme 53: Oxyarylation of alkenes with arylsilanes and IBA as reoxidant.
PEG-embedded KBr3: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines
- Sanny Verma,
- Suman L. Jain and
- Bir Sain
Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157
Graphical Abstract
Scheme 1: Synthesis of [K+PEG]Br3−.
Scheme 2: Synthesis of functionalized piperidines.
Figure 1: X-ray structure showing the anti orientation of the phenyl rings at C2 and C6.
Scheme 3: A plausible mechanism for the formation of piperidines.
