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Search for "Green Chemistry" in Full Text gives 233 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds
- Vasudevan Dhayalan
Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200
- , has emerged as a versatile and robust model for the sustainable synthesis of carbonyl groups and related valued organic compounds. This cooperative photochemical strategy offers broad functional group tolerance and operational simplicity. It aligns with green chemistry principles by operating under
Graphical Abstract
Scheme 1: NHC-catalyzed umpolung strategy for the metal-free synthesis of amide via dual catalysis.
Scheme 2: Visible-light promoted cooperative NHC/photoredox catalyzed ring-opening of aryl cyclopropanes.
Scheme 3: NHC-catalyzed benzylic C–H acylation by dual catalysis.
Scheme 4: NHC/photoredox-catalyzed three-component coupling reaction for the preparation of γ-aryloxy ketones....
Scheme 5: NHC-catalyzed silyl radical generation from silylboronate via dual catalysis.
Scheme 6: NHC-catalyzed C–H acylation of arenes and heteroarenes through photocatalysis.
Scheme 7: NHC-catalyzed iminoacylation of alkenes via photoredox dual organocatalysis.
Scheme 8: NHC/photoredox catalyzed direct synthesis of β-arylketoesters.
Scheme 9: Visible-light-driven NHC/photoredox catalyzed borylacylation of alkenes.
Scheme 10: NHC-catalyzed oxidative functionalization of cinnamaldehyde.
Scheme 11: NHC/photocatalyzed oxidative Smiles rearrangement.
Scheme 12: NHC-catalyzed synthesis of cyclohexanones through photocatalyzed annulation.
Scheme 13: Dual organocatalyzed meta-selective acylation of electron-rich arenes and heteroarenes using blue L...
Scheme 14: Asymmetric synthesis of fused pyrrolidinones via organophotoredox/N‑heterocyclic carbene dual catal...
Palladium-catalyzed regioselective C1-selective nitration of carbazoles
- Vikash Kumar,
- Jyothis Dharaniyedath,
- Aiswarya T P,
- Sk Ariyan,
- Chitrothu Venkatesh and
- Parthasarathy Gandeepan
Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190
- NiCl2/NaBH4 in methanol at room temperature, affording the corresponding amine 4 in 93% yield. To align with green chemistry principles, we employed a recently reported mechanochemical protocol by Ito and co-workers for the reduction of nitro compounds to amines [72]. Using this solvent-free method
Graphical Abstract
Scheme 1: (a) Representative examples of bioactive nitrocarbazoles. (b) Traditional electrophilic aromatic su...
Figure 1: ORTEP diagram of compound 2a (CCDC 2478298).
Scheme 2: Effect of directing groups on the nitration of the carbazoles.
Scheme 3: Scope of the method. Reaction conditions: 1 (0.2 mmol, 1.0 equiv), Pd2(dba)3 (0.02 mmol, 10 mol %),...
Scheme 4: Gram-scale synthesis, directing group removal, and synthetic utility of our method.
Scheme 5: Key mechanistic studies.
Figure 2: Plausible catalytic cycle.
Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds
- Natalya Akhmetdinova,
- Ilgiz Biktagirov and
- Liliya Kh. Faizullina
Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185
- can be used to synthesize complex and unique compounds that cannot be produced by thermal reactions, making photochemical transformations preferable to classical ones, especially when considering the concept of «green chemistry» [73]. Therefore, photochemical rearrangements have great theoretical and
Graphical Abstract
Scheme 1: Ozonolysis–cyclization sequence in the synthesis of echinopine A (3).
Scheme 2: Ozonolysis–cyclization sequence in the synthesis of taiwaniaquinoids 7–12.
Figure 1: Iridoid skeleton.
Scheme 3: Ozonolysis–cyclization sequence in the synthesis of compounds 17a,b, 18 and 19 with iridoid topolog...
Scheme 4: Oxidation–aldol condensation sequence in the synthesis of compounds 21 and 23 with iridoid topology....
Scheme 5: Oxidation–aldol condensation sequence in the synthesis of compounds 29 and 30 with iridoid topology....
Scheme 6: Method for ring contraction in the absence of a double bond in a six-membered ring of triterpenoids....
Scheme 7: Oxidation–Dieckmann cyclization sequence in the synthesis of a new nortriterpenoid 39.
Scheme 8: Oxidation–Dieckmann cyclization sequence in the synthesis of 18,19-di-nor-cholesterol (40).
Scheme 9: Oxidation–cyclization sequence in the synthesis of 3-ethyl-substituted betulinic acid derivatives 49...
Scheme 10: Benzilic acid-type rearrangement in the synthesis of 4β-acetoxyprobotryane-9β,15α-diol (52).
Scheme 11: Benzilic acid-type rearrangement in the synthesis of (−)-taiwaniaquinone H (11).
Scheme 12: Benzilic acid-type rearrangement in the synthesis of dactylicapnosines A (63) and B (64).
Scheme 13: Aza-benzilic acid-type rearrangement in the synthesis of (+)-stephadiamine (71).
Scheme 14: α-Ketol rearrangement in the synthesis of saffloneoside (73).
Scheme 15: Conversion of (−)-preaustinoid A (80) to (−)-preaustinoid B (81) via α-ketol rearrangement.
Scheme 16: α-Ketol rearrangement in the synthesis of 2,8-oxymethano-bridged diquinane 90.
Scheme 17: Oxidative ring contraction during the synthesis of (+)-cuparene (91) and (+)-tochuinylacetate (92).
Scheme 18: Semipinacol rearrangement in the synthesis of diterpenoids 97–100.
Scheme 19: Co-catalyzed homoallyl-type rearrangement in the syntheses of meroterpenes 106–109.
Scheme 20: Ring contraction reaction promoted by TTN·3H2O and HTIB in the synthesis of indanes.
Scheme 21: Rearrangement involving a hypervalent iodine compound in the synthesis of derivative 120.
Scheme 22: Wolff rearrangement in the synthesis of taiwaniaquinones A (7), F (8), taiwaniaquinols B (10), D (1...
Scheme 23: Wolff rearrangement in the synthesis of cheloviolene C (128), seconorrisolide B (129), and seconorr...
Scheme 24: Wolff rearrangement in the synthesis of (−)-pavidolide B (134).
Scheme 25: Wolff rearrangement in the synthesis of presilphiperfolan-8-ol (141).
Scheme 26: Photochemical rearrangement in the synthesis of cyclopentane derivatives 147a,b.
Scheme 27: Synthesis of cyclopentane derivatives 147a and 151.
Scheme 28: Photochemical rearrangement in the synthesis of cyclopentane derivative 153.
Scheme 29: Photochemical rearrangement in the synthesis of tricyclic ketones 155, 156.
Scheme 30: Photochemical rearrangement in the synthesis of cis/trans salts 160.
Figure 2: Scope of the photoinduced carboborative ring contraction of steroids. Reaction conditions: steroid ...
Scheme 31: Photoinduced carboborative ring contraction in the synthesis of artalbic acid (180).
Scheme 32: Synthetic versatility of the photoinduced carboborative ring contraction.
Scheme 33: Methods of disclosure of epoxide 189.
Scheme 34: Methods of disclosure of epoxide 190.
Scheme 35: Rearrangement of α,β-epoxy ketone 197.
Scheme 36: Acid-induced rearrangement in the synthesis of perhydrindane ketones 202 and 205.
Scheme 37: Rearrangement of epoxyketone 208 in the synthesis of huperzine Q (206).
Scheme 38: Rearrangement of epoxide 212 under the action of Grignard reagent.
Scheme 39: Semipinacol rearrangement of epoxide 220 in the synthesis of (−)-citrinadin A (217) and (+)-citrina...
Scheme 40: Semipinacol rearrangement of epoxide 225 in the synthesis of hamigeran G (223).
Scheme 41: Semipinacol rearrangement of epoxide 231 in the synthesis of (−)-spirochensilide A (228).
Scheme 42: Wagner–Meerwein rearrangement in the synthesis of compound 234 with iridoid topology.
Scheme 43: Wagner–Meerwein rearrangement in the synthesis of compound 238 with iridoid topology.
Scheme 44: Wagner–Meerwein rearrangement in the synthesis of compound 241 with iridoid topology.
Scheme 45: Wagner–Meerwein rearrangement in the synthesis of lupane derivatives 245, 246, 248, and 249.
Scheme 46: Wagner–Meerwein rearrangement in the synthesis of weisaconitine D (252) and cardiopetaline (255).
Scheme 47: Wagner–Meerwein rearrangement in the synthesis of cardiopetaline (255).
The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions
- Ayhan Yıldırım and
- Mustafa Göker
Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184
- ]. It is therefore a basic tenet of Green Chemistry to replace the conventional organic solvents, which are flammable and generate toxic volatile components and are costly, with readily accessible and biocompatible alternatives [71]. Indeed, the utilization of eco-friendly bio-based solvents in a
- cylinder chart in Figure 7. Indeed, a significant proportion of the experimentally measured Green Chemistry parameters for methyl laurate are consistent with the predictions of various software or web platforms, and in some cases, even demonstrate that certain toxicity parameters of methyl laurate are more
- is fully consumed by the end of the five-minute reaction period. In academic and industrial communities alike, there is a high level of interest in catalytic methods of Green Chemistry that allow stereoselective transformations [125][126][127][128]. It is imperative to develop stereoselective
Graphical Abstract
Figure 1: Versatile compounds via cycloaddition reactions.
Scheme 1: Molecular structures of parent compounds 1a–f, 2a–d and cycloadducts 3a–u.
Figure 2: a) Radar view of the physical properties of methyl laurate. b) Oral toxicity values of methyl laura...
Figure 3: The oral toxicity values of all the solvents utilized in the present study obtained with ProTox 3.0....
Figure 4: Ecological, environmental risk assessments, pesticide similarity and biodegradability assessments o...
Figure 5: Ecological, environmental risk assessments, pesticide similarity and biodegradability assessments o...
Figure 6: Ecological, environmental risk assessments, pesticide similarity and biodegradability assessments o...
Figure 7: Various toxicity parameters of methyl laurate and a series of other solvents calculated by ADMETLab...
Figure 8: a) Visualization of the localization of conventional organic and bio-based solvents in the Hansen s...
Figure 9: Vapour pressures of the solvents used (values retrieved from the Chemeo molecular database).
Scheme 2: Endo and exo stereoisomeric approaches of nitrone 1a and maleimide 2a in [3 + 2] cycloaddition reac...
Figure 10: Signals of protons used in the calculation of the diastereomeric ratios (cis/trans) of cycloadditio...
Figure 11: Results of studies on the recovery of solvents used in the reaction.
Figure 12: Simplified scheme describing the reaction monitoring and solvent recovery.
Figure 13: a) The superimposed spectra of C,N-diphenylnitrone and N-phenylmaleimide. b) The spectrum of methyl...
Pathway economy in cyclization of 1,n-enynes
- Hezhen Han,
- Wenjie Mao,
- Bin Lin,
- Maosheng Cheng,
- Lu Yang and
- Yongxiang Liu
Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173
- rapid molecular diversification, offering transformative potential for green chemistry and pharmaceutical applications. By unifying mechanistic insights with practical synthetic design, this review provides valuable guidance for future innovations in precision organic synthesis. Keywords: economical
- platform, as exemplified by recent breakthroughs in polycyclic skeleton construction and stereo-divergent cyclization. The implementation of pathway economy fosters significant advancements in green chemistry by minimizing synthetic steps, reducing waste generation, and enhancing atom economy. Notably
Graphical Abstract
Scheme 1: Economical synthesis and pathway economy.
Scheme 2: Au(I)-catalyzed cascade cyclization paths of 1,5-enynes.
Scheme 3: Au(I)-catalyzed cyclization paths of 1,7-enynes.
Scheme 4: I2/TBHP-mediated radical cycloisomerization paths of 1,n-enyne.
Scheme 5: Au(I)-catalyzed cycloisomerization paths of 3-allyloxy-1,6-diynes.
Scheme 6: Pd(II)-catalyzed cycloisomerization paths of 2-alkynylbenzoate-cyclohexadienone.
Scheme 7: Stereoselective cyclization of 1,5-enynes.
Scheme 8: Substituent-controlled cycloisomerization of propargyl vinyl ethers.
Scheme 9: Au(I)-catalyzed pathway-controlled domino cyclization of 1,2-diphenylethynes.
Scheme 10: Au(I)-catalyzed tandem cyclo-isomerization of tryptamine-N-ethynylpropiolamide.
Scheme 11: Au(I)-catalyzed tunable cyclization of 1,6-cyclohexenylalkyne.
Scheme 12: Substituent-controlled 7-exo- and 8-endo-dig-selective cyclization of 2-propargylaminobiphenyl deri...
Scheme 13: BiCl3-catalyzed cycloisomerization of tryptamine-ynamide derivatives.
Scheme 14: Au(I)-mediated substituent-controlled cycloisomerization of 1,6-enynes.
Scheme 15: Ligand-controlled regioselective cyclization of 1,6-enynes.
Scheme 16: Ligand-dependent cycloisomerization of 1,7-enyne esters.
Scheme 17: Ligand-controlled cycloisomerization of 1,5-enynes.
Scheme 18: Ligand-controlled cyclization strategy of alkynylamide tethered alkylidenecyclopropanes.
Scheme 19: Ag(I)-mediated pathway-controlled cycloisomerization of tryptamine-ynamides.
Scheme 20: Gold-catalyzed cycloisomerization of indoles with alkynes.
Scheme 21: Catalyst-dependent cycloisomerization of dienol silyl ethers.
Scheme 22: Cycloisomerization of aromatic enynes governed by catalyst.
Scheme 23: Catalyst-dependent 1,2-migration in cyclization of 1-(indol-2-yl)-3-alkyn-1-ols.
Scheme 24: Gold-catalyzed cycloisomerization of N-propargyl-N-vinyl sulfonamides.
Scheme 25: Gold(I)-mediated enantioselective cycloisomerizations of ortho-(alkynyl)styrenes.
Scheme 26: Catalyst-controlled intramolecular cyclization of 1,7-enynes.
Scheme 27: Brønsted acid-catalyzed cycloisomerizations of tryptamine ynamides.
Scheme 28: Catalyst-controlled cyclization of indolyl homopropargyl amides.
Scheme 29: Angle strain-dominated 6-endo-trig cyclization of propargyl vinyl ethers.
Scheme 30: Angle strain-controlled cycloisomerization of alkyn-tethered indoles.
Scheme 31: Geometrical isomeration-dependent cycloisomerization of 1,3-dien-5-ynes.
Scheme 32: Temperature-controlled cyclization of 1,7-enynes.
Scheme 33: Cycloisomerizations of n-(o-ethynylaryl)acrylamides through temperature modulation.
Scheme 34: Temperature-controlled boracyclization of biphenyl-embedded 1,3,5-trien-7-ynes.
Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions
- Xiaoming Ma,
- Zijie Gao,
- Jiawei Niu,
- Wentao Shao,
- Shenghu Yan,
- Sai Zhang and
- Wei Zhang
Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167
- Xiaoming Ma Zijie Gao Jiawei Niu Wentao Shao Shenghu Yan Sai Zhang Wei Zhang School of Pharmacy, Changzhou University, 1 Gehu Road, Changzhou 213164, China Department of Chemistry and Center for Green Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA 10.3762
Graphical Abstract
Figure 1: Some bioactive molecules bearing triazole, tetrazole, and 1,4-benzodiazepin rings.
Scheme 1: Ugi–azide reaction for the synthesis of 1,5-DS-T-containing heterocycles.
Scheme 2: Proposed Ugi–azide-initiated synthesis of polyheterocyclic scaffolds 7 and 8.
Scheme 3: 4-CR vs stepwise Ugi–azide reactions for the synthesis of 7a.
Scheme 4: Synthesis of benzodiazepines 7a–k. Reaction conditions: 1) 0.2 mmol each of 2-azidobenzaldehyde (1a...
Scheme 5: Synthesis of polycyclic compound 8a.
Scheme 6: Synthesis of product analogs 8. Reaction conditions: 1) 0.2 mmol each of 2-azidobenzaldehyde (1a) a...
Scheme 7: Control reactions to trap the Ugi–azide adduct.
Figure 2: 1H NMR spectra of compounds 6a (red) and 8a (blue).
Scheme 8: Gram-scale one-pot synthesis of 8a.
Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings
- Lifen Peng,
- Ting Wang,
- Zhiwen Yuan,
- Bin Li,
- Zilong Tang,
- Xirong Liu,
- Hui Li,
- Guofang Jiang,
- Chunling Zeng,
- Henry N. C. Wong and
- Xiao-Shui Peng
Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166
- transformations far from thermodynamic equilibria have emerged abundantly with the consideration of green chemistry [89][90][91][92]. Redox-active organic compounds, transition metal coordinating compounds and even an electrode surface were commonly employed as catalysts in the electrochemical transformations [93
Graphical Abstract
Figure 1: Natural products and functional molecules possessing five-membered rings.
Scheme 1: Electrochemical intramolecular coupling of ureas to form indoles.
Scheme 2: Electrochemical dehydrogenative annulation of alkynes with anilines.
Scheme 3: Electrochemical annulations of o-arylalkynylanilines.
Scheme 4: Electrochemical cyclization of 2-ethynylanilines.
Scheme 5: Electrochemical selenocyclization of diselenides and 2-ethynylanilines.
Scheme 6: Electrochemical cascade approach towards 3-selenylindoles.
Scheme 7: Electrochemical C–H indolization.
Scheme 8: Electrochemical annulation of benzamides and terminal alkynes.
Scheme 9: Electrochemical synthesis of isoindolinone by 5-exo-dig aza-cyclization.
Scheme 10: Electrochemical reductive cascade annulation of o-alkynylbenzamide.
Scheme 11: Electrochemical intramolecular 1,2-amino oxygenation of alkyne.
Scheme 12: Electrochemical multicomponent reaction of nitrile, (thio)xanthene, terminal alkyne and water.
Scheme 13: Electrochemical aminotrifluoromethylation/cyclization of alkynes.
Scheme 14: Electrochemical cyclization of o-nitrophenylacetylene.
Scheme 15: Electrochemical annulation of alkynyl enaminones.
Scheme 16: Electrochemical annulation of alkyne and enamide.
Scheme 17: Electrochemical tandem Michael addition/azidation/cyclization.
Scheme 18: Electrochemical [3 + 2] cyclization of heteroarylamines.
Scheme 19: Electrochemical CuAAC to access 1,2,3-triazole.
C2 to C6 biobased carbonyl platforms for fine chemistry
- Jingjing Jiang,
- Muhammad Noman Haider Tariq,
- Florence Popowycz,
- Yanlong Gu and
- Yves Queneau
Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165
- : aldehydes; biobased chemistry; biomass; carbonyl; fine chemicals; ketones; multicomponent; platforms; sustainability; Introduction Shifting towards sustainable practices in the chemical industry relies on continued advancement of green chemistry sciences which aim to minimize the global environmental
- impact while maintaining the efficiency of the chemical processes [1]. Green Chemistry principles outlined by Anastas and Warner in their work “Green Chemistry: Theory and Practice (2000)” [2] notably highlight atom economy, waste minimization and the use of renewable feedstock as pillars of sustainable
Graphical Abstract
Figure 1: C2–C6 biobased carbonyl building blocks.
Scheme 1: Proposed (2 + 2) route to glycolaldehyde and glycolic acid from erythritol by Cu/AC catalyst (AC = ...
Scheme 2: Reductive amination of GCA.
Scheme 3: N-Formylation of secondary amines by reaction with GCA.
Scheme 4: Synthesis and conversion of hydroxy acetals to cyclic acetals.
Scheme 5: Synthesis of 3-(indol-3-yl)-2,3-dihydrofurans via three-component reaction of glycolaldehyde, indol...
Scheme 6: BiCl3-catalyzed synthesis of benzo[a]carbazoles from 2-arylindoles and α-bromoacetaldehyde ethylene...
Scheme 7: Cu/NCNSs-based conversion of glycerol to glycolic acid and other short biobased acids.
Scheme 8: E. coli-based biotransformation of C1 source molecules (CH4, CO2 and CO) towards C2 glycolic acid.
Scheme 9: N-Formylation of amines with C2 (a) or C3 (b) biomass-based feedstocks.
Scheme 10: Methods for the formation of propanoic acid (PA) from lactic acid (LA).
Scheme 11: Co-polymerization of biobased lactic acid and glycolic acid via a bicatalytic process.
Scheme 12: Oxidation of α-hydroxy acids by tetrachloroaurate(III) in acetic acid–sodium acetate buffer medium.
Figure 2: Selective catalytic pathways for the conversion of lactic acid (LA).
Scheme 13: Synthesis of 1,3-PDO via cross-aldol reaction between formaldehyde and acetaldehyde to 3-hydroxypro...
Scheme 14: Hydrothermal conversion of 1,3-dihydroxy-2-propane and 2,3-dihydroxypropanal to methylglyoxal.
Scheme 15: FLS-catalyzed formose reaction to synthesize GA and DHA.
Scheme 16: GCA and DHA oxidation products of glycerol and isomerization of GCA to DHA under flow conditions us...
Scheme 17: Acid-catalyzed reactions of DHA with alcohols.
Scheme 18: Synthesis of dihydroxyacetone phosphate from dihydroxyacetone.
Scheme 19: Bifunctional acid–base catalyst DHA conversion into lactic acid via pyruvaldehyde or fructose forma...
Scheme 20: Catalytic one-pot synthesis of GA and co-synthesis of formamides and formates from DHA.
Scheme 21: (a) Synthesis of furan derivatives and (b) synthesis of thiophene derivative by cascade [3 + 2] ann...
Scheme 22: Brønsted acidic ionic liquid catalyzed synthesis of benzo[a]carbazole from renewable acetol and 2-p...
Scheme 23: Asymmetric hydrogenation of α-hydroxy ketones to 1,2-diols.
Scheme 24: Synthesis of novel 6-(substituted benzylidene)-2-methylthiazolo [2,3-b]oxazol-5(6H)-one from 1-hydr...
Scheme 25: ʟ-Proline-catalyzed synthesis of anti-diols from hydroxyacetone and aldehydes.
Scheme 26: C–C-bond-formation reactions of a biomass-based feedstock aromatic aldehyde (C5) and hydroxyacetone...
Scheme 27: Ethanol upgrading to C4 bulk chemicals via the thiamine (VB1)-catalyzed acetoin condensation.
Scheme 28: One-pot sequential chemoenzymatic synthesis of 2-aminobutane-1,4-diol and 1,2,4-butanetriol via 1,4...
Scheme 29: Synthesis of 1,4-dihydroxybutan-2-one by microbial transformation.
Scheme 30: Conversion of polyols by [neocuproine)Pd(OAc)]2(OTf)2] to α-hydroxy ketones.
Scheme 31: Chemoselective oxidation of alcohols with chiral palladium-based catalyst 2.
Scheme 32: Electrochemical transformation of furfural to 5-hydroxy-2(5H)-furanone (HFO).
Scheme 33: Selective hydrodeoxygenation of HFO and oxidation to γ-butyrolactone (GBL).
Scheme 34: Photosensitized oxygenation of furan towards HFO via ozonide intermediates.
Scheme 35: Conversion of furfural to HFO and MAN by using mesoporous carbon nitride (SGCN) as photocatalyst.
Scheme 36: Synthesis of HFO from furan derivatives.
Scheme 37: Photooxidation of furfural to 5-hydroxy-2(5H)-furanone (HFO).
Scheme 38: Synthesis of Friedel–Crafts indole adduct from HFO.
Scheme 39: Conversion of HFO to α,γ-substituted chiral γ-lactones.
Scheme 40: Tautomeric transformation of HFO to formylacrylic acid.
Scheme 41: Hydrolysis of HFO to succinic acid in aqueous solution.
Scheme 42: Substitution and condensation reactions of 5-hydroxy-2(5H)-furanone (HFO).
Scheme 43: (a) Conversion of HFO towards valuable C4 chemicals and (b) anodic oxidation of 5-hydroxy-2(5H)-fur...
Figure 3: Conversion of HFO towards other natural and synthetic substances.
Scheme 44: Conversion of furfural to maleic anhydride (reaction a: VOx/Al2O3; reaction b: VPO).
Scheme 45: Conversion of furfural into succinic acid.
Scheme 46: Electro‑, photo‑, and biocatalysis for one-pot selective conversions of furfural into C4 chemicals.
Scheme 47: Production route of furfural from hemicellulose.
Scheme 48: Mechanism for xylose dehydration to furfural through a choline xyloside intermediate.
Scheme 49: Conversion of furfural to furfuryl alcohol and its derivatives.
Scheme 50: Conversion of furfural to furfuryl alcohol and 3-(2-furyl)acrolein.
Scheme 51: The aerobic oxidative condensation of biomass-derived furfural and linear alcohols.
Scheme 52: The single-step synthesis of 2-pentanone from furfural.
Scheme 53: Electrocatalytic coupling reaction of furfural and levulinic acid.
Scheme 54: Conversion of furfural to m-xylylenediamine.
Scheme 55: Conversion of furfural to tetrahydrofuran-derived amines.
Scheme 56: Formation of trans-4,5-diamino-cyclopent-2-enones from furfural.
Scheme 57: Production of pyrrole and proline from furfural.
Scheme 58: Synthesis of 1‑(trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones from furfural.
Scheme 59: Conversion of furfural to furfural-derived diacids.
Scheme 60: A telescope protocol derived from furfural and glycerol.
Scheme 61: A tandem cyclization of furfural and 5,5-dimethyl-1,3-cyclohexanedione.
Scheme 62: A Ugi four-component reaction to construct furfural-based polyamides.
Scheme 63: One-pot synthesis of γ-acyloxy-Cy7 from furfural.
Scheme 64: Dimerization–Piancatelli sequence toward humins precursors from furfural.
Scheme 65: Conversion of furfural to CPN.
Scheme 66: Synthesis of jet fuels range cycloalkanes from CPN and lignin-derived vanillin.
Scheme 67: Solar-energy-driven synthesis of high-density biofuels from CPN.
Scheme 68: Reductive amination of CPN to cyclopentylamine.
Scheme 69: Asymmetric hydrogenation of C=O bonds of exocyclic α,β-unsaturated cyclopentanones.
Scheme 70: Preparation of levulinic acid via the C5 route (route a) or C6 route (routes b1 and b2).
Scheme 71: Mechanism of the rehydration of HMF to levulinic acid and formic acid.
Scheme 72: Important levulinic acid-derived chemicals.
Scheme 73: Direct conversion of levulinic acid to pentanoic acid.
Scheme 74: Catalytic aerobic oxidation of levulinic acid to citramalic acid.
Scheme 75: Conversion of levulinic acid to 1,4-pentanediol (a) see ref. [236]; b) see ref. [237]; c) see ref. [238]; d) see r...
Scheme 76: Selective production of 2-butanol through hydrogenolysis of levulinic acid.
Scheme 77: General reaction pathways proposed for the formation of 5MPs from levulinic acid.
Scheme 78: Selective reductive amination of levulinic acid to N-substituted pyrroles.
Scheme 79: Reductive amination of levulinic acid to chiral pyrrolidinone.
Scheme 80: Reductive amination of levulinic acid to non-natural chiral γ-amino acid.
Scheme 81: Nitrogen-containing chemicals derived from levulinic acid.
Scheme 82: Preparation of GVL from levulinic acid by dehydration and hydrogenation.
Scheme 83: Ruthenium-catalyzed levulinic acid to chiral γ-valerolactone.
Scheme 84: Catalytic asymmetric hydrogenation of levulinic acid to chiral GVL.
Scheme 85: Three steps synthesis of ε-caprolactam from GVL.
Scheme 86: Multistep synthesis of nylon 6,6 from GVL.
Scheme 87: Preparation of MeGVL by α-alkylation of GVL.
Scheme 88: Ring-opening polymerization of five-membered lactones.
Scheme 89: Synthesis of GVL-based ionic liquids.
Scheme 90: Preparation of butene isomers from GVL under Lewis acid conditions.
Scheme 91: Construction of C5–C12 fuels from GVL over nano-HZSM-5 catalysts.
Scheme 92: Preparation of alkyl valerate from GVL via ring opening/reduction/esterification sequence.
Scheme 93: Construction of 4-acyloxypentanoic acids from GVL.
Scheme 94: Synthesis of 1,4-pentanediol (PDO) from GVL.
Scheme 95: Construction of novel cyclic hemiketal platforms via self-Claisen condensation of GVL.
Scheme 96: Copper-catalyzed lactamization of GVL.
Figure 4: Main scaffolds obtained from HMF.
Scheme 97: Biginelli reactions towards HMF-containing dihydropyrimidinones.
Scheme 98: Hantzsch dihydropyridine synthesis involving HMF.
Scheme 99: The Kabachnik–Fields reaction involving HMF.
Scheme 100: Construction of oxazolidinone from HMF.
Scheme 101: Construction of rhodamine-furan hybrids from HMF.
Scheme 102: A Groebke–Blackburn–Bienaymé reaction involving HMF.
Scheme 103: HMF-containing benzodiazepines by [4 + 2 + 1] cycloadditions.
Scheme 104: Synthesis of fluorinated analogues of α-aryl ketones.
Scheme 105: Synthesis of HMF derived disubstituted γ-butyrolactone.
Scheme 106: Functionalized aromatics from furfural and HMF.
Scheme 107: Diels–Alder adducts from HMF or furfural with N-methylmaleimide.
Scheme 108: Pathway of the one-pot conversion of HMF into phthalic anhydride.
Scheme 109: Photocatalyzed preparation of humins (L-H) from HMF mixed with spoiled HMF residues (LMW-H) and fur...
Scheme 110: Asymmetric dipolar cycloadditions on HMF.
Scheme 111: Dipolar cycloadditions of HMF based nitrones to 3,4- and 3,5-substituted isoxazolidines.
Scheme 112: Production of δ-lactone-fused cyclopenten-2-ones from HMF.
Scheme 113: Aza-Piancatelli access to aza-spirocycles from HMF-derived intermediates.
Scheme 114: Cross-condensation of furfural, acetone and HMF into C13, C14 and C15 products.
Scheme 115: Base-catalyzed aldol condensation/dehydration sequences from HMF.
Scheme 116: Condensation of HMF and active methylene nitrile.
Scheme 117: MBH reactions involving HMF.
Scheme 118: Synthesis of HMF-derived ionic liquids.
Scheme 119: Reductive amination/enzymatic acylation sequence towards HMF-based surfactants.
Scheme 120: The formation of 5-chloromethylfurfural (CMF).
Scheme 121: Conversion of CMF to HMF, levulinic acid, and alkyl levulinates.
Scheme 122: Conversion of CMF to CMFCC and FDCC.
Scheme 123: Conversion of CMF to BHMF.
Scheme 124: Conversion of CMF to DMF.
Scheme 125: CMF chlorine atom substitutions toward HMF ethers and esters.
Scheme 126: Introduction of carbon nucleophiles in CMF.
Scheme 127: NHC-catalyzed remote enantioselective Mannich-type reactions of CMF.
Scheme 128: Conversion of CMF to promising biomass-derived dyes.
Scheme 129: Radical transformation of CMF with styrenes.
Scheme 130: Synthesis of natural herbicide δ-aminolevulinic acid from CMF.
Scheme 131: Four step synthesis of the drug ranitidine from CMF.
Scheme 132: Pd/CO2 cooperative catalysis for the production of HHD and HXD.
Scheme 133: Different ruthenium (Ru) catalysts for the ring-opening of 5-HMF to HHD.
Scheme 134: Proposed pathways for preparing HXD from HMF.
Scheme 135: MCP formation and uses.
Scheme 136: Cu(I)-catalyzed highly selective oxidation of HHD to 2,5-dioxohexanal.
Scheme 137: Synthesis of N‑substituted 3‑hydroxypyridinium salts from 2,5-dioxohexanal.
Scheme 138: Ru catalyzed hydrogenations of HHD to 1,2,5-hexanetriol (a) see ref. [396]; b) see ref. [397]).
Scheme 139: Aviation fuel range quadricyclanes produced by HXD.
Scheme 140: Synthesis of HDGK from HXD and glycerol as a chain extender.
Scheme 141: Synthesis of serinol pyrrole from HXD and serinol.
Scheme 142: Synthesis of pyrroles from HXD and nitroarenes.
Scheme 143: Two-step production of PX from cellulose via HXD.
Scheme 144: Preparation of HCPN from HMF via hydrogenation and ring rearrangement.
Scheme 145: Suggested pathways from HMF to HCPN.
Scheme 146: α-Alkylation of HCPN with ethylene gas.
Scheme 147: Synthesis of 3-(hydroxymethyl)cyclopentylamine from HMF via reductive amination of HCPN.
Scheme 148: Production of LGO and Cyrene® from biomass.
Scheme 149: Synthesis of HBO from LGO and other applications.
Scheme 150: Construction of m-Cyrene® homopolymer.
Scheme 151: Conversion of Cyrene® to THFDM and 1,6-hexanediol.
Scheme 152: RAFT co-polymerization of LGO and butadienes.
Scheme 153: Polycondensation of HO-LGOL and diols with dimethyl adipate.
Scheme 154: Self-condensation of Cyrene® and Claisen–Schmidt reactions.
Scheme 155: Synthesis of 5-amino-2-(hydroxymethyl)tetrahydropyran from Cyrene®.
Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines
- Margherita Gazzotti,
- Fabrizio Medici,
- Valerio Chiroli,
- Laura Raimondi,
- Sergio Rossi and
- Maurizio Benaglia
Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147
- applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural
Graphical Abstract
Scheme 1: Synthesis of vicinal diamines via imino-pinacol coupling in the presence of metal-based reductants.
Scheme 2: Light-promoted imino-pinacol coupling for the synthesis of vicinal diamines.
Scheme 3: Historical perspective on electrochemical imino-coupling protocols.
Scheme 4: Stereoselective electroreductive intramolecular imino-pinacol reaction.
Scheme 5: Scope of the imino-pinacol coupling reaction. Reaction conditions: GC electrodes, NEt4BF4 (2.6 equi...
Figure 1: X-ray determined structure of chiral piperazine 2b.
Scheme 6: Continuous flow synthesis of piperazine 2a. The yield was determined by 1H NMR spectroscopy using 1...
Scheme 7: Proposed reaction mechanism.
Scheme 8: Cyclic voltammetry investigation. Cyclic voltammetry of a 0.325 M solution of Et4NBF4 in DMF (light...
Influence of the cation in hypophosphite-mediated catalyst-free reductive amination
- Natalia Lebedeva,
- Fedor Kliuev,
- Olesya Zvereva,
- Klim Biriukov,
- Evgeniya Podyacheva,
- Maria Godovikova,
- Oleg I. Afanasyev and
- Denis Chusov
Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130
- , usage of classical reducing agents – H2 on Pd/C or NaBH4 did not show similar chemoselectivity [26]. Additionally, the NaH2PO2 usability is engaging due to fine green chemistry metrics, e.g., an E-factor less than 1 was reached, moreover the main wastes of this process were safe and useful as
Graphical Abstract
Scheme 1: Rationale of the current study: a) Our previous work [20]; b) this work.
Scheme 2: Comparison of KH2PO2 and NaH2PO2 under the optimal conditions.
Figure 1: Substrate scope. Reaction conditions: carbonyl compound (1.45 mmol, 1 equiv), amine (1.81 mmol, 1.2...
Scheme 3: Control experiments.
Scheme 4: Experiments with D3PO2.
Scheme 5: Principal steps of the mechanism of the reductive amination with K2CO3/H3PO2 reducing system.
Figure 2: Reaction profile and DFT energies of intermediates and transition states. M062X functional with the...
General method for the synthesis of enaminones via photocatalysis
- Paula Pérez-Ramos,
- Raquel G. Soengas and
- Humberto Rodríguez-Solla
Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116
- ]. Thus, the use of visible light as an energy source provides more efficient chemical transformations and minimize the use of harmful reagents, the generation of waste and the consumption of energy, fulfilling several principles of Green Chemistry and promoting greener opportunities for organic synthesis
Graphical Abstract
Figure 1: Examples of compounds with medicinal effects containing an enaminone structural moiety.
Scheme 1: Synthesis of enaminones.
Scheme 2: Substrate scope.
Scheme 3: Scale-up synthesis of enaminone 9a.
Scheme 4: Mechanistic studies.
Scheme 5: Proposed mechanism.
Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper
- Andrei Paraschiv,
- Valentina Maruzzo,
- Filippo Pettazzi,
- Stefano Magliocco,
- Paolo Inaudi,
- Daria Brambilla,
- Gloria Berlier,
- Giancarlo Cravotto and
- Katia Martina
Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108
- -amination of benzoxazoles by transition-metal-catalysed reactions that traditionally involve aryl halide scaffolds [11][12][13][14]. However, these procedures entail disadvantages that need to be overcome if green chemistry criteria are to be met; high temperatures, long reaction times, the need for ligands
Graphical Abstract
Scheme 1: Representative synthetic routes for the C–H amination of benzoxazole using supported copper catalys...
Figure 1: Reaction of benzimidazole with piperidine. a) Reaction scheme including intermaidates and b) conver...
Figure 2: Reaction rate comparison between conventional (oil bath) and MW heating. Reaction conditions: benzo...
Scheme 2: Graphical representation of Si-MonoAm-Cu(I) and Si-DiAm-Cu(I) preparation.
Figure 3: TGA profiles of SIPERNAT silica and Si-MonoAm and Si-DiAm.
Scheme 3: Scope of the MW-promoted C2-amination of benzoxazole catalysed by Si-MonoAm-Cu(I). Reaction conditi...
Scheme 4: C2-Amination of substituted benzoxazoles. Reaction conditions: benzoxazole (1.0 mmol), piperidine (...
Figure 4: Hot filtration test for the Si-MonoAm-Cu(I)-catalysed C2-amination of benzoxazole with piperidine i...
Figure 5: FTIR spectra of samples on the left 3800–2400 cm−1 wavenumber on the right 1750–1350 cm−1 wavenumbe...
Figure 6: Si-MonoAm-Cu(I) catalyst reuse.
Figure 7: FESEM images of sample a) Si-MonoAm-Cu(I) 5 wt % and c) Si-MonoAm-Cu(I) 5 wt % used.
Figure 8: EDS maps of a) Si-MonoAm-Cu(I) and b) Si-MonoAm-Cu(I) used.
High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters
- Kelsey Plasse,
- Valerie Wright,
- Guoshu Xie,
- R. Bernadett Vlocskó,
- Alexander Lazarev and
- Béla Török
Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102
- still offered a reasonable increase in rates and thus, in yields. In addition to the synthetic advantages, the benefits HHP offers can also translate to green chemistry. The use of HHP extends the scope of solvent-, reagent- and catalyst-free reactions that significantly reduce workup and waste
Graphical Abstract
Figure 1: Simplified schematic rendering of a high hydrostatic pressure reactor.
Scheme 1: High pressure-initiated synthesis of 1,3-dihydrobenzimidazoles 3a–d. The yields are GC yields and t...
Figure 2: Illustration of the cyclization reaction between chalcone (4) and 3-(trifluoromethyl)phenylhydrazin...
Scheme 2: High pressure-initiated catalyst- and solvent-free synthesis of pyrazoles 6a–c from chalcone (4) an...
Figure 3: Schematic representation of the cycling experiments: the major variables are the applied pressure, ...
Scheme 3: High pressure-initiated synthesis of the active pharmaceutical ingredients in Tylenol® and Aspirin®...
Scheme 4: High pressure-initiated esterification of alcohols 12a–g in a catalyst- and additional solvent-free...
Scheme 5: High pressure-initiated large scale syntheses of N-aryl- and N-alkylpyrroles at about 100 g scale.
Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer
- Hao-Sen Wang,
- Lin Li,
- Xin Chen,
- Jian-Li Wu,
- Kai Sun,
- Xiao-Lan Chen,
- Ling-Bo Qu and
- Bing Yu
Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100
- and the relatively green chemistry of generating amidyl radicals. Amidyl radicals offer several advantages that enhance their applicability in organic synthesis: 1) The BDE of amidyl N–H bond is more than 105 kcal/mol, relative to the bond (C–H, Si–H, B–H, and Ge–H) which BDE is lower than 100 kcal
- the research of direct functionalization via HAT processes and the development of green chemistry in photocatalysis, this review will focus on the generation of amidyl radicals and reaction mechanisms and highlight the photocatalyzed reaction characteristics. This review aims to provide researchers
- reaction; however, such extreme conditions limited the practical applicability of the reactions. To address this limitation, Alexanian's research has shifted toward the principles of green chemistry, utilizing visible light to achieve mild reaction conditions. This approach has not only enhanced the
Graphical Abstract
Figure 1: (a) BDE of C–H. (b) Direct functionalization of C–H catalyzed by transition-metal. (c) Direct funct...
Figure 2: (a) Amidyl radical-enabled hydrogen atom transfer. (b) Substituent effects to amidyl radical proper...
Figure 3: Representative photocatalysts discussed in this review.
Scheme 1: Alkylation of C(sp3)–H catalyzed by amidyl radical under visible light.
Scheme 2: Direct heteroarylation of C(sp3)–H catalyzed by amidyl radical under visible light.
Scheme 3: Alkylation of C(sp3)–H catalyzed by amidyl radical and metal-free photocatalyst under visible light....
Scheme 4: Alkylation of C(sp3)–H, Si–H, and Ge–H catalyzed by amidyl radical under visible light.
Scheme 5: Direct heteroarylation of C(sp3)–H catalyzed by synergistic promotion of amidyl radical and photoca...
Scheme 6: Direct B–H functionalization of icosahedral carboranes catalyzed by amidyl radical under visible li...
Scheme 7: Nucleophilic amination of C(sp3)–H enabled by amidyl radical under visible light.
Scheme 8: Direct heteroarylation of C(sp3)–H and C(sp3)–H without the presence of strong bases, acids, or oxi...
Scheme 9: Xanthylation of C(sp3)–H addressed by amidyl radical under visible light.
Scheme 10: Xanthylation of C(sp3)–H in polyolefins addressed by amidyl radical under visible light.
Scheme 11: Site-selective C(sp3)–H bromination implemented by amidyl radical under visible light.
Scheme 12: Site-selective chlorination of C(sp3)–H in natural products implemented by amidyl radical under vis...
Scheme 13: Alkylation of C(sp3)–H catalyzed by amidyl radical photocatalyst under visible light.
Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents
- Jiangfei Chen,
- Yi-Lin Qu,
- Ming Yuan,
- Xiang-Mei Wu,
- Heng-Pei Jiang,
- Ying Fu and
- Shengrong Guo
Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98
- from N-cyanamide alkenes (Scheme 27) [16]. This approach is notable for its alignment with the principles of green chemistry, utilizing the metal-free photocatalyst 4CzIPN under visible light conditions. In this system, N-cyanamide alkene 54 and BrCF2CO2Et 55 were used as model substrates, with 4CzIPN
Graphical Abstract
Scheme 1: DTBP-mediated oxidative alkylarylation of activated alkenes.
Scheme 2: Iron-catalyzed oxidative 1,2-alkylarylation.
Scheme 3: Possible mechanism for the iron-catalyzed oxidative 1,2-alkylation of activated alkenes.
Scheme 4: A metal-free strategy for synthesizing 3,3-disubstituted oxindoles.
Scheme 5: Iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkenes.
Scheme 6: Proposed mechanism for the iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkene...
Scheme 7: Bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 8: Possible reaction mechanism for the bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 9: Radical cyclization of N-arylacrylamides with isocyanides.
Scheme 10: Plausible mechanism for the radical cyclization of N-arylacrylamides with isocyanides.
Scheme 11: Electrochemical dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 12: Plausible mechanism for the dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 13: Photocatalyzed cyclization of N-arylacrylamide and N,N-dimethylaniline.
Scheme 14: Proposed mechanism for the photocatalyzed cyclization of N-arylacrylamides and N,N-dimethylanilines....
Scheme 15: Electrochemical monofluoroalkylation cyclization of N-arylacrylamides with dimethyl 2-fluoromalonat...
Scheme 16: Proposed mechanism for the electrochemical radical cyclization of N-arylacrylamides with dimethyl 2...
Scheme 17: Photoelectrocatalytic carbocyclization of unactivated alkenes using simple malonates.
Scheme 18: Plausible mechanism for the photoelectrocatalytic carbocyclization of unactivated alkenes with simp...
Scheme 19: Bromide-catalyzed electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 20: Proposed mechanism for the electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 21: Visible light-mediated trifluoromethylarylation of N-arylacrylamides.
Scheme 22: Plausible reaction mechanism for the visible light-mediated trifluoromethylarylation of N-arylacryl...
Scheme 23: Electrochemical difluoroethylation cyclization of N-arylacrylamides with sodium difluoroethylsulfin...
Scheme 24: Electrochemical difluoroethylation cyclization of N-methyacryloyl-N-alkylbenzamides with sodium dif...
Scheme 25: Photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)su...
Scheme 26: Proposed mechanism for the photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamide...
Scheme 27: Visible-light-induced domino difluoroalkylation/cyclization of N-cyanamide alkenes.
Scheme 28: Proposed mechanism of photoredox-catalyzed radical domino difluoroalkylation/cyclization of N-cyana...
Scheme 29: Palladium-catalyzed oxidative difunctionalization of alkenes.
Scheme 30: Two possible mechanisms of palladium-catalyzed oxidative difunctionalization.
Scheme 31: Silver-catalyzed oxidative 1,2-alkyletherification of unactivated alkenes with α-bromoalkylcarbonyl...
Scheme 32: Photochemical radical cascade cyclization of dienes.
Scheme 33: Proposed mechanism for the photochemical radical cascade 6-endo cyclization of dienes with α-carbon...
Scheme 34: Photocatalyzed radical coupling/cyclization of N-arylacrylamides and.
Scheme 35: Photocatalyzed radical-type couplings/cyclization of N-arylacrylamides with sulfoxonium ylides.
Scheme 36: Possible mechanism of visible-light-induced radical-type couplings/cyclization of N-arylacrylamides...
Scheme 37: Visible-light-promoted difluoroalkylated oxindoles systhesis via EDA complexes.
Scheme 38: Possible mechanism for the visible-light-promoted radical cyclization of N-arylacrylamides with bro...
Scheme 39: A dicumyl peroxide-initiated radical cascade reaction of N-arylacrylamide with DCM.
Scheme 40: Possible mechanism of radical cyclization of N-arylacrylamides with DCM.
Scheme 41: An AIBN-mediated radical cascade reaction of N-arylacrylamides with perfluoroalkyl iodides.
Scheme 42: Possible mechanism for the reaction with perfluoroalkyl iodides.
Scheme 43: Photoinduced palladium-catalyzed radical annulation of N-arylacrylamides with alkyl halides.
Scheme 44: Radical alkylation/cyclization of N-Alkyl-N-methacryloylbenzamides with alkyl halides.
Scheme 45: Possible mechanism for the alkylation/cyclization with unactivated alkyl chlorides.
Scheme 46: Visible-light-driven palladium-catalyzed radical cascade cyclization of N-arylacrylamides with unac...
Scheme 47: NHC-catalyzed radical cascade cyclization of N-arylacrylamides with alkyl bromides.
Scheme 48: Possible mechanism of NHC-catalyzed radical cascade cyclization.
Scheme 49: Electrochemically mediated radical cyclization reaction of N-arylacrylamides with freon-type methan...
Scheme 50: Proposed mechanistic pathway of electrochemically induced radical cyclization reaction.
Scheme 51: Redox-neutral photoinduced radical cascade cylization of N-arylacrylamides with unactivated alkyl c...
Scheme 52: Proposed mechanistic hypothesis of redox-neutral radical cascade cyclization.
Scheme 53: Thiol-mediated photochemical radical cascade cylization of N-arylacrylamides with aryl halides.
Scheme 54: Proposed possible mechanism of thiol-mediated photochemical radical cascade cyclization.
Scheme 55: Visible-light-induced radical cascade bromocyclization of N-arylacrylamides with NBS.
Scheme 56: Possible mechanism of visible-light-induced radical cascade cyclization.
Scheme 57: Decarboxylation/radical C–H functionalization by visible-light photoredox catalysis.
Scheme 58: Plausible mechanism of visible-light photoredox-catalyzed radical cascade cyclization.
Scheme 59: Visible-light-promoted tandem radical cyclization of N-arylacrylamides with N-(acyloxy)phthalimides....
Scheme 60: Plausible mechanism for the tandem radical cyclization reaction.
Scheme 61: Visible-light-induced aerobic radical cascade alkylation/cyclization of N-arylacrylamides with alde...
Scheme 62: Plausible mechanism for the aerobic radical alkylarylation of electron-deficient amides.
Scheme 63: Oxidative decarbonylative [3 + 2]/[5 + 2] annulation of N-arylacrylamide with vinyl acids.
Scheme 64: Plausible mechanism for the decarboxylative (3 + 2)/(5 + 2) annulation between N-arylacrylamides an...
Scheme 65: Rhenium-catalyzed alkylarylation of alkenes with PhI(O2CR)2.
Scheme 66: Plausible mechanism for the rhenium-catalyzed decarboxylative annulation of N-arylacrylamides with ...
Scheme 67: Visible-light-induced one-pot tandem reaction of N-arylacrylamides.
Scheme 68: Plausible mechanism for the visible-light-initiated tandem synthesis of difluoromethylated oxindole...
Scheme 69: Copper-catalyzed redox-neutral cyanoalkylarylation of activated alkenes with cyclobutanone oxime es...
Scheme 70: Plausible mechanism for the copper-catalyzed cyanoalkylarylation of activated alkenes.
Scheme 71: Photoinduced alkyl/aryl radical cascade for the synthesis of quaternary CF3-attached oxindoles.
Scheme 72: Plausible photoinduced electron-transfer (PET) mechanism.
Scheme 73: Photoinduced cerium-mediated decarboxylative alkylation cascade cyclization.
Scheme 74: Plausible reaction mechanism for the decarboxylative radical-cascade alkylation/cyclization.
Scheme 75: Metal-free oxidative tandem coupling of activated alkenes.
Scheme 76: Control experiments and possible mechanism for 1,2-carbonylarylation of alkenes with carbonyl C(sp2...
Scheme 77: Silver-catalyzed acyl-arylation of activated alkenes with α-oxocarboxylic acids.
Scheme 78: Proposed mechanism for the decarboxylative acylarylation of acrylamides.
Scheme 79: Visible-light-mediated tandem acylarylation of olefines with carboxylic acids.
Scheme 80: Proposed mechanism for the radical cascade cyclization with acyl radical via visible-light photored...
Scheme 81: Erythrosine B-catalyzed visible-light photoredox arylation-cyclization of N-arylacrylamides with ar...
Scheme 82: Electrochemical cobalt-catalyzed radical cyclization of N-arylacrylamides with arylhydrazines or po...
Scheme 83: Proposed mechanism of radical cascade cyclization via electrochemical cobalt catalysis.
Scheme 84: Copper-catalyzed oxidative tandem carbamoylation/cyclization of N-arylacrylamides with hydrazinecar...
Scheme 85: Proposed reaction mechanism for the radical cascade cyclization by copper catalysis.
Scheme 86: Visible-light-driven radical cascade cyclization reaction of N-arylacrylamides with α-keto acids.
Scheme 87: Proposed mechanism of visible-light-driven cascade cyclization reaction.
Scheme 88: Peroxide-induced radical carbonylation of N-(2-methylallyl)benzamides with methyl formate.
Scheme 89: Proposed cyclization mechanism of peroxide-induced radical carbonylation with N-(2-methylallyl)benz...
Scheme 90: Persulfate promoted carbamoylation of N-arylacrylamides and N-arylcinnamamides.
Scheme 91: Proposed mechanism for the persulfate promoted radical cascade cyclization reaction of N-arylacryla...
Scheme 92: Photocatalyzed carboacylation with N-arylpropiolamides/N-alkyl acrylamides.
Scheme 93: Plausible mechanism for the photoinduced carboacylation of N-arylpropiolamides/N-alkyl acrylamides.
Scheme 94: Electrochemical Fe-catalyzed radical cyclization with N-arylacrylamides.
Scheme 95: Plausible mechanism for the electrochemical Fe-catalysed radical cyclization of N-phenylacrylamide.
Scheme 96: Substrate scope of the selective functionalization of various α-ketoalkylsilyl peroxides with metha...
Scheme 97: Proposed reaction mechanism for the Fe-catalyzed reaction of alkylsilyl peroxides with methacrylami...
Scheme 98: EDA-complex mediated C(sp2)–C(sp3) cross-coupling of TTs and N-methyl-N-phenylmethacrylamides.
Scheme 99: Proposed mechanism for the synthesis of oxindoles via EDA complex.
A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones
- Ashutosh Nath,
- John Mark Awad and
- Wei Zhang
Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92
- –Bienaymé (GBB); imidazopyridine; intramolecular Diels–Alder (IMDA); isoquinolinone; multicomponent reaction (MCR); re-aromatization; Introduction Multicomponent reactions (MCRs) have intrinsic green chemistry advantages of synthetic efficiency and operational simplicity. Performing post-condensational
Graphical Abstract
Figure 1: Bioactive compounds bearing imidazopyridine (red) and isoquinolinone-kind (blue) rings.
Scheme 1: GBB-initiated synthesis of imidazopyridine-fused isoquinolinones.
Scheme 2: GBB reaction and N-acylation for the preparation of imidazo[1,2-a]pyridines 6.
Scheme 3: Substrate scope for IMDA and dehydrative aromatization in making 8. Reaction conditions: 6 and AlCl3...
Figure 2: Transition state analysis of IMDA reactions for 6a, 6j, 6h and 6r.
Figure 3: Relative energy diagram for the synthesis of 8a from 6a.
Scheme 4: Using thiophene-2-carbaldehyde for the synthesis of 8t.
Scheme 5: Proposed mechanisms for IMDA reaction and dehydration re-aromatization.
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
- /N-acylation reactions, metal catalysts, particularly precious transition metals, are considered less sustainable due to their limited availability. Therefore, metal-free catalysis methods have emerged as an alternative to respond to the green chemistry agenda. For instance, Huy and Mbouhom (2019
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.
Recent advances in controllable/divergent synthesis
- Jilei Cao,
- Leiyang Bai and
- Xuefeng Jiang
Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73
- Jilei Cao Leiyang Bai Xuefeng Jiang Hainan Institute of East China Normal University, State Key Laboratory of Petroleum Molecular & Process Engineering, Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University
Graphical Abstract
Scheme 1: Ligand-controlled regiodivergent C1 insertion into arynes [19].
Scheme 2: Ligand effect in homogenous gold catalysis enabling regiodivergent π-bond-activated cyclization [20].
Scheme 3: Ligand-controlled palladium(II)-catalyzed regiodivergent carbonylation of alkynes [21].
Scheme 4: Catalyst-controlled annulations of strained cyclic allenes with π-allyl palladium complexes and pro...
Scheme 5: Ring expansion of benzosilacyclobutenes with alkynes [23].
Scheme 6: Photoinduced regiodivergent and enantioselective cross-coupling [24].
Scheme 7: Catalyst-controlled regiodivergent and enantioselective formal hydroamination of N,N-disubstituted ...
Scheme 8: Catalyst-tuned regio- and enantioselective C(sp3)–C(sp3) coupling [31].
Scheme 9: Catalyst-controlled annulations of bicyclo[1.1.0]butanes with vinyl azides [32].
Scheme 10: Solvent-driven reversible macrocycle-to-macrocycle interconversion [39].
Scheme 11: Unexpected solvent-dependent reactivity of cyclic diazo imides and mechanism [40].
Scheme 12: Palladium-catalyzed annulation of prochiral N-arylphosphonamides with aromatic iodides [41].
Scheme 13: Time-dependent enantiodivergent synthesis [42].
Scheme 14: Time-controlled palladium-catalyzed divergent synthesis of silacycles via C–H activation [43].
Scheme 15: Proposed mechanism for the time-controlled palladium-catalyzed divergent synthesis of silacycles [43].
Scheme 16: Metal-free temperature-controlled regiodivergent borylative cyclizations of enynes [45].
Scheme 17: Nickel-catalyzed switchable site-selective alkene hydroalkylation by temperature regulation [46].
Scheme 18: Copper-catalyzed decarboxylative amination/hydroamination sequence [48].
Scheme 19: Proposed mechanism of copper-catalyzed decarboxylative amination/hydroamination sequence [48].
Scheme 20: Enantioselective chemodivergent three-component radical tandem reactions [49].
Scheme 21: Substrate-controlled synthesis of indoles and 3H-indoles [52].
Scheme 22: Controlled mono- and double methylene insertions into nitrogen–boron bonds [53].
Scheme 23: Copper-catalyzed substrate-controlled carbonylative synthesis of α-keto amides and amides [54].
Scheme 24: Divergent sulfur(VI) fluoride exchange linkage of sulfonimidoyl fluorides and alkynes [55].
Scheme 25: Modular and divergent syntheses of protoberberine and protonitidine alkaloids [56].
Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water
- Wei-Jin Chang,
- Sook Yee Liew,
- Thomas Kurz and
- Siow-Ping Tan
Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46
- exceptional functional group tolerance, accommodating phenyl, aliphatic, phenol, alcohol, heterocyclic, and sulfide groups. This scalable, rapid, and eco-friendly strategy offers a promising avenue for the efficient synthesis of hydantoins, aligning with green chemistry principles and expanding the
- advantages over conventional heating, such as enhanced reaction rates and yields [17]. Microwave irradiation is also aligned with our group’s sustainability goals of adhering to the principles of green chemistry [18]. Following our previous works in the synthesis and evaluation of biologically active
- demonstrate that the process can be effectively scaled up, particularly in industries that prioritize sustainability and operational efficiency. In terms of green chemistry principles, this approach already meets several key goals, such as reducing the use of hazardous reagents and solvents, increasing
Graphical Abstract
Scheme 1: N-Carbamylation of ʟ-phenylaniline using KOCN in water.
Scheme 2: One-pot microwave-assisted synthesis of hydantoins from amino acids.
Figure 1: Hydantoins (H2a–j) synthesized from the one-pot procedure. The hydantoins were characterized using 1...
Formaldehyde surrogates in multicomponent reactions
- Cecilia I. Attorresi,
- Javier A. Ramírez and
- Bernhard Westermann
Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45
- concerns and improved reaction control can be addressed, paving the way for more efficient and sustainable synthetic methodologies. Keywords: cascade reactions; formaldehyde surrogates; green chemistry; heterocycles; multicomponent reactions; Introduction Organic chemistry is a mature discipline that has
- temperatures, no specifically prepared solvents), one-pot, batch processes leading to tandem or cascade reactions, resource efficiency through the application of the 12 principles of Green Chemistry, and readily available starting materials such as waste materials from food production processes [1][2][3]. In
Graphical Abstract
Scheme 1: Features of the ideal reaction (redrawn from P. A. Wender et al. [1]).
Scheme 2: Some of the most popular MCRs with formaldehyde as the carbonyl component.
Scheme 3: Ugi reaction under a catalyzed electro-oxidation process using TEMPO (2,2,6,6-tetramethyl-1-piperid...
Scheme 4: Examples of different products obtained by MCRs in which DMSO serves as -SCH3 source.
Scheme 5: Mechanism of the decomposition of DMSO under acidic or thermal conditions. a) In situ generation of...
Scheme 6: Povarov multicomponent reaction to quinolines.
Scheme 7: Example of the Povarov reaction with formaldehyde with a julolidine derivative as main product.
Scheme 8: Povarov multicomponent reaction to quinoline derivatives I and II using DMSO as formaldehyde surrog...
Scheme 9: Example of a Povarov three-component reaction with change of catalyst, yielding regioisomer III. In...
Scheme 10: The Povarov three-component reactions carried out under acidic catalysis to afford quinoline regios...
Scheme 11: Different MCR routes involving DMSO to synthesize complex heterocycles such as diarylpyridines and ...
Scheme 12: Pyrazole synthesis by a three-component reaction using DMSO as a source of a C-1 unit.
Scheme 13: Three-component reactions for the synthesis of aliphatic heterocycles 13 and 14 using DMSO as a for...
Scheme 14: Proposed mechanism for the 3CR between homoallylic amines, disulfides, and DMSO.
Scheme 15: Mannich-type reaction using DMSO as formaldehyde surrogate.
Scheme 16: Mechanism for the 3CR-Mannich-type reaction between aryl ketone 18, saccharine (19), and DMSO. The ...
Scheme 17: Mannich-type reaction using DMSO as formaldehyde surrogate and under oxidative activation.
Scheme 18: Three-component reaction between an indazole, a carboxylic acid, and DMSO.
Scheme 19: Amine–aldehyde–alkyne (AAA) coupling reaction and plausible mechanism.
Scheme 20: AHA coupling for the synthesis of propargylamines using dihalomethanes as C1 building blocks.
Scheme 21: AHA coupling using CH2Cl2 as both solvent and methylene source.
Scheme 22: Examples of propargylamines synthesized under catalytic AHA protocols.
Scheme 23: Proposed mechanism for the synthesis of propargylamines using dichloromethane as a C1 source.
Scheme 24: Mechanism proposed for the generation of the aminal intermediate E by Buckley et al. [68].
Scheme 25: Pudovic and Kabachnik–Fields reactions for the synthesis of α-aminophosphonates.
Scheme 26: a) Abramov side reaction that generates α-hydroxy phosphonate as a byproduct during the Kabachnik-F...
Scheme 27: Catalyst-free three component reaction to afford α-amino phosphorus product 35 using 1,1-dihaloalka...
Scheme 28: a) Proposed mechanism for the three-component reaction of dichloromethane, amine and phosphorus com...
Scheme 29: Ugi-ammonia strategy using HMTA as a formaldehyde surrogate.
Scheme 30: Glyoxylate and its derivatives as C1 building blocks.
Scheme 31: The Groebke–Blackburn–Bienaymé multicomponent reaction (GBB) and its mechanism.
Scheme 32: a) Byproducts in the GBB multicomponent reaction (GBB) when formaldehyde is used as the carbonyl co...
Scheme 33: Possible regioisomers in the GBB multicomponent reaction when formaldehyde is used as the carbonyl ...
Scheme 34: The multicomponent GBB reaction yields 2-unsubstituted 3-aminoimidazo heterocycles 42a using MP-gly...
Scheme 35: GBB multicomponent reaction to 2-unsubstituted 3-amino imidazo heterocycles 42a using glyoxylic aci...
Scheme 36: GBB reaction using glyoxylic acid immobilized on silica as formaldehyde surrogate.
Scheme 37: Bioactive products synthesized by the GBB reaction using glyoxylic acid.
Scheme 38: van Leusen three-component reaction to imidazoles.
Scheme 39: Side reaction during the synthesis of imidazoles with formaldehyde as the carbonyl compound.
Scheme 40: Optimization of the van Leusen three component reaction to 1,4-disubstituted imidazoles 43 using gl...
Scheme 41: Application of the Sisko strategy [96] for the synthesis of CB1 receptor antagonist compounds [97].
Scheme 42: Side reaction, when NH4OH is used as amine component.
Scheme 43: Ugi-type adducts with the ester moiety and the acidic CH to be used for post-cyclization sequences.
Scheme 44: Ugi/cycloisomerization process to pyrrolones 51, butenolides 52, and pyrroline 53.
Scheme 45: Radical cyclization reactions from Ugi adducts promoted by TEMPO.
Scheme 46: Hydrolysis and decarboxylation reactions to products with incorporation of a C1 unit of ethyl glyox...
Scheme 47: One-step synthetic route to pyrrolones 60 using phenylglyoxal.
Scheme 48: Ugi-pseudo-Knoevenagel-pseudo-Dieckmann cascade sequence for the synthesis of fused heterocycles.
Scheme 49: Ugi-pseudo-Knoevenagel reaction from ethyl glyoxylate.
Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye
- Metodej Dvoracek,
- Brendan Twamley,
- Mathias O. Senge and
- Mikhail A. Filatov
Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37
- crystal lattice and are often reversible, requiring either high-energy light or heat for initiation [6][7][8]. Notably, topochemical polymerizations align with the principles of green chemistry, as they are solvent-free and do not involve toxic reagents [9]. The highly ordered and uniform nature of
Graphical Abstract
Figure 1: Structures of a) the unfunctionalized bimane scaffold and b) the two isomers of bimanes with their ...
Figure 2: a) Structures of the bimanes studied and b) the reaction scheme of the [2 + 2] photocycloaddition o...
Figure 3: Synthetic approach to bimanes.
Figure 4: View of the molecular structures in the crystal of the functionalized bimanes studied: a) Cl2B (B),...
Figure 5: View of the molecular structure in the crystal of a) symmetry generated by inversion bimanes Cl2B (...
Figure 6: View of the packing of the unit cells of a) Me2B viewed normal to the c-axis and b) Me4B viewed nor...
Figure 7: UV–vis spectrum of Cl2B after irradiation in DCM.
Figure 8: Proposed mechanism for the topochemical [2 + 2] photocycloaddition of Cl2B.
Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions
- Francesco Mele,
- Ana M. Constantin,
- Andrea Porcheddu,
- Raimondo Maggi,
- Giovanni Maestri,
- Nicola Della Ca’ and
- Luca Capaldo
Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33
- developed, where additional energy is applied to increase mixing such as pulsation [26][27][28], ultrasound energy [29], segmented flow [30], or mechanical stirring [31]. In line with the recent emphasis on Green Chemistry principles [32][33], alternatives have been developed in order to reduce the amount
Graphical Abstract
Figure 1: The Grotthuss–Draper, Einstein–Stark, and Beer–Lambert laws. T: transmittance; ε: molar attenuation...
Figure 2: The benefits of merging photochemistry with mechanochemical setups (top). Most common setups for ph...
Scheme 1: Mechanochemically triggered pedal-like motion in solid-state [2 + 2] photochemical cycloaddition fo...
Scheme 2: Mechanically promoted [2 + 2] photodimerization of trans-1,2-bis(4-pyridyl)ethylene (2.1) via supra...
Scheme 3: Photo-thermo-mechanosynthesis of quinolines [65].
Scheme 4: Study of the mechanically assisted [2 + 2] photodimerization of chalcone [66].
Scheme 5: Liquid-assisted vortex grinding (LAVG) for the synthesis of [2.2]paracyclophane [68].
Scheme 6: Photomechanochemical approach for the riboflavin tetraacetate-catalyzed photocatalytic oxidation of...
Scheme 7: Photomechanochemical oxidation of 1,2-diphenylethyne to benzil. The photo in Scheme 7 was republished with ...
Scheme 8: Photomechanochemical borylation of aryldiazonium salts. The photo in Scheme 8 was reproduced from [72] (© 2017 ...
Scheme 9: Photomechanochemical control over stereoselectivity in the [2 + 2] dimerization of acenaphthylene. ...
Scheme 10: Photomechanochemical synthesis of polyaromatic compounds using UV light. The photo in Scheme 10 was reproduc...
Scheme 11: Mechanically assisted photocatalytic reactions: A) atom-transfer-radical addition, B) pinacol coupl...
Scheme 12: Use of mechanoluminescent materials as photon sources for photomechanochemistry. SAOED: SrAl2O4:Eu2+...
Figure 3: SWOT (strengths, weaknesses, opportunities, threats) analysis of photomechanochemistry.
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
- chemistry with significant potential in synthetic and biomedical fields. Keywords: green chemistry; medicinal chemistry; organic photochemistry; photocatalysis; red-light mediated transformations; Introduction Red-light-activated photocatalysis has recently gained significant interest as a tool for
- underscores the practicality and accessibility of the method, even outside a laboratory setting. The green chemistry metrics analysis provided in the study confirms the environmental benefits, with high atom economy, low waste generation, minimal resource consumption, and the potential of porphyrin
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.
Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts
- Beatriz Dedeiras,
- Catarina S. Caldeira,
- José C. Cunha,
- Clara S. B. Gomes and
- M. Manuel B. Marques
Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272
- thank the Fundação para a Ciência e Tecnologia (FCT, project 2022.04623.PTDC, fellowship 2022.11629.BD (J.C.). The authors also thank the support by the Associate Laboratory for Green Chemistry – LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 DOI 10.54499/UIDB/50006/2020, UIDP
Graphical Abstract
Figure 1: Examples of cyclic HIRs with a nitrogen-based group transfer [4,10,13-20].
Scheme 1: Electrophilic α‑amination of indanone-based β-ketoesters [4].
Scheme 2: Scope of the different (benzylamino)benziodoxolones (BBXs) 2 with ORTEP-3 diagram of compound 2d, u...
Scheme 3: Scope of the different β-sulfinyl esters 4 [32,33]. Isolated yields. rt – room temperature.
Scheme 4: Scope of the primary amine electrophilic reaction of sulfenate salts. Reaction conditions: 4 (2 equ...
Scheme 5: Electrophilic amination reaction in the presence of TEMPO. Reaction conditions: 4a (2 equiv), NaH (...
Scheme 6: Mechanism proposed for sulfonamide 5, β-sulfinyl ester 4, disulfide 7, and sulfide 3 formations. Th...
Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling
- Jiapeng Guo,
- Weike Su and
- An Su
Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205
- University of Technology, Hangzhou, 310014, P. R. China State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key Laboratory of Green Chemistry-Synthesis Technology of Zhejiang Province, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
Graphical Abstract
Figure 1: The schematic diagram of the continuous flow microreactor system.
Scheme 1: Nitration of IO with mixed acid.
Figure 2: Two mixing setups: (a) a T-mixer and (b) a T-mixer combined with a homemade static mixer, and the e...
Figure 3:
Determination of the number of reaction orders. a) ln(1−xIO) versus t; b) ![[Graphic 1]](/bjoc/content/inline/1860-5397-20-205-i17.svg?max-width=637&scale=1.18182)
versus t; c) ln(1−xIO) v...
Figure 4: Determination of (M−1)cIO0k at different temperatures and H2SO4 mass fractions. (a) 88% H2SO4, (b) ...
Figure 5: Variations and fitting of as a function of a) the mass fraction of H2SO4 at 23 °C, 40 °C, and 60 °C...
Figure 6: Determination of thermodynamic parameters n and k0 and determination of the activation energy and p...
Figure 7: a) The value of apparent rate constant k at various H2SO4 mass fractions and different temperatures...
