Search results
Search for "DBU" in Full Text gives 314 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K
- Liangyu Liu,
- Wanqiu Lu,
- Quanping Guo and
- Zhaoqing Xu
Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202
- resin as the solid support, enabling mild cleavage of the partially protected linear peptide precursor [21]. Efficient Fmoc deprotection was achieved using a solution of 1% pyridine and 1% 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in N,N-dimethylformamide (DMF) [22]. For the assembly of the linear
Graphical Abstract
Scheme 1: Preparation of segetalins A–H, J and K.
Figure 1: Cyclization reactions to segetalins A–H, J and K.
Figure 2: The CD spectra of segetalins A–H, J and K.
Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate
- Roman A. Irgashev
Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191
- formation of carboxylic acid 9bA, isolated in 71% yield (Scheme 7). In addition, an attempt to cyclize 6b in the presence of DBU without a solvent at 110 °C led to significant destruction of the substrate and product 9b was obtained with a yield of about 20%. Cyclization of substrate 4a with NaH in toluene
Graphical Abstract
Scheme 1: The synthetic routes to 3-hydroxy-substituted TT derivatives.
Scheme 2: The present retrosynthetic plan for constructing TT molecules.
Scheme 3: An attempt to nucleophilically substitute the NO2 group in ester 1.
Scheme 4: The reaction of ester 1 with potassium thioacetate.
Scheme 5: A probable mechanism for the formation of compounds 2 and 3.
Scheme 6: The synthesis of 3-(alkylthio)thiophene-2,5-dicarboxylates 4–6, yields, and scope of products. *Fro...
Scheme 7: The synthesis of TT derivatives, yields, and scope of products. Conditions: i) LiH (5 equiv), DMF, ...
Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis
- Nikolai B. Akselvoll,
- Jonas T. Larsen and
- Christian M. Pedersen
Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188
- used building blocks in glycosylations. For the synthesis chamber (A) was loaded with trifluoroacetamide (6 equiv) in pyridine. In the other chamber (B), the hemiacetal (ca. 500 mg, 1 equiv) was dissolved in CH2Cl2 together with a catalytic amount of DBU. Upon addition of trifluoroacetic anhydride
- is not easily done as the system is now under pressure. The chamber was then opened to release excess gas (on small scale) and the product in chamber B can be obtained by concentration and purification. The use of other bases than DBU, was also investigated. Similar to the synthesis of
- trichloroacetimidates K2CO3 was effective for the synthesis of β-acetimidates [26], whereas polystyrene-supported DBU [27] was found to be less effective and DBU was therefore the preferred catalyst. The synthesis of perbenzylated α-glucosyl trifluoroacetimidate 3 proceeded in 52% yield on a preparative scale, with DBU
Graphical Abstract
Figure 1: Examples of methods for the synthesis of trifluoroacetonitrile and our set-up using a two-chamber r...
Scheme 1: Reactions in chambers A and B. Chamber A: generation of the haloacetonitrile by dehydration of the ...
Figure 2: Glycosyl haloacetimidates synthesized using the two-chamber method.
Figure 3: Synthesis of arylmethylene fluoroacetimidates using the two-chamber method.
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
- ]undec-7-ene (DBU) in benzene resulted in high yield of β-hydroxyaldehyde 6. Through a series of synthetic transformations, the target products (−)-taiwaniaquinones A (7), F (8), G (9), and H (11), (−)-taiwaniaquinol B (10) and (−)-dichroanone (12) were obtained from intermediate 6 (Scheme 2). An
- destruction of the main amount of dialdehyde, cyclopentanediol 21 was isolated with a yield of 24%. This synthetic block is promising for the synthesis of gibboside (22) [20]. Following the second direction, ozonolysis of the double bond in compound 14 and subsequent treatment of the ozonide with DBU resulted
- acid (DMOA), are a large series of hybrid natural products with a huge structural diversity and impressive biological activity [50]. Attempts by the authors to use acidic (TiCl4, TMSI, SnCl4), basic (NaOMe, t-BuONa, Et3N, DBU, DMAP) and thermal conditions (PhMe, 110 °C) failed to give the desired
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).
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
- at the anode to generate imine intermediate C. Simultaneously, treatment of 39a with I+ and the following intramolecular nucleophilic cyclization produced C. The elimination of a proton from C afforded the intermediate D. In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), the intramolecular
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
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®.
The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products
- Dong-Xing Tan and
- Fu-She Han
Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164
- 69 and lactone 70 at 456 nm with fac-Ir(ppy)3 as the photocatalyst furnished a mixture of isomeric olefins. Finally, DBU-promoted the isomeric olefins conjugation and removal of the two silyl ether completed the first total synthesis of (+)-randainin D (13). Total synthesis of (−)-hunterine A and
Graphical Abstract
Figure 1: Several representative terpenoid and alkaloid natural products synthesized by applying desymmetric ...
Figure 2: Selected terpenoid and alkaloid natural products synthesized by applying desymmetric enantioselecti...
Scheme 1: The total synthesis of (+)-aplysiasecosterol A (6) by Li [14].
Scheme 2: The total synthesis of (−)-cyrneine A by Han [31].
Scheme 3: The total syntheses of three cyrneine diterpenoids by Han [31,32].
Scheme 4: The total synthesis of (−)-hamigeran B and (−)-4-bromohamigeran B by Han [51].
Scheme 5: The total synthesis of (+)-randainin D by Baudoin [53].
Scheme 6: The total synthesis of (−)-hunterine A and (−)-aspidospermidine by Stoltz [58].
Scheme 7: The total synthesis of (+)-toxicodenane A by Han [65,66].
Scheme 8: The formal total synthesis of (−)-conidiogeone B and total synthesis of (−)-conidiogeone F by Lee a...
Scheme 9: The total syntheses of four conidiogenones natural products by Lee and Han [72].
Scheme 10: The total synthesis of (−)-platensilin by Lou and Xu [82].
Scheme 11: The total synthesis of (−)-platencin and (−)-platensimycin by Lou and Xu [82].
Scheme 12: The total synthesis of (+)-isochamaecydin and (+)-chamaecydin by Han [86].
Bioinspired total syntheses of natural products: a personal adventure
- Zhengyi Qin,
- Yuting Yang,
- Nuran Yan,
- Xinyu Liang,
- Zhiyu Zhang,
- Yaxuan Duan,
- Huilin Li and
- Xuegong She
Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160
- additions, respectively. This result suggests that the addition fully went from the upper face and the left-oriented isopropyl showed no steric effect to control the regioselectivity. With free amide 50a and 50b in hand, the mixture was treated with DBU to promote aza-Michael addition to afford lactam
Graphical Abstract
Figure 1: Representative natural products with biomimetic total synthesis.
Scheme 1: Bioinspired total synthesis of chabranol (2010).
Scheme 2: Proposed biosynthetic pathway of monocerin-family natural products.
Scheme 3: Bioinspired total synthesis of monocerin-family molecules (2013).
Scheme 4: Bioinspired skeletal diversification of (12-MeO-)tabertinggine (2016).
Scheme 5: Structures and our proposed biosynthetic pathway of gymnothelignans.
Scheme 6: Bioinspired total synthesis of gymnothelignans (2014–2025).
Scheme 7: Bioinspired total synthesis of sarglamides (2025).
Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation
- Shuhai Qiu and
- Junzhi Liu
Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149
- could be viewed as the aza[14]metacyclophane derivatives, in which two benzene rings are replaced by two pyrenes. The Pd-catalyzed arylation of 3a with Pd(OAc)2, PMe(t-Bu)2·HBF4 and DBU under microwave conditions gave two isomeric macrocycles MC1 and MC2 with four newly formed C–C bonds in yields of 5
- . Synthesis of N-doped macrocycles MC1, MC2, and MC3. Reaction conditions: a) Pd2(dba)3, Pt-Bu3·HBF4, NaOt-Bu, toluene, 110 °C, 24 h. 3a: 16%; 3b: 10%. b) Pd(OAc)2, PMe(t-Bu)2·HBF4, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), DMAc, microwave, 170 °C, 5 h. MC1: 5%; MC2: 90%; MC3: 85%. Supporting Information
Graphical Abstract
Figure 1: (a) Representatives of inherent chiral calix[4]arenes. (b) Molecular skeletons of inherent chiral N...
Scheme 1: Synthesis of N-doped macrocycles MC1, MC2, and MC3. Reaction conditions: a) Pd2(dba)3, Pt-Bu3·HBF4,...
Figure 2: Crystal structures of compounds (a) 3a, (b) MC2, and (c) MC3. (d) Molecular arrangements of MC3. Hy...
Figure 3: (a) Absorptions and (b) emissions of compounds 3a, 3b, MC1, MC2, and MC3 measured in dichloromethan...
Figure 4: Calculated frontier molecular orbitals and relative energy levels of MC1 (left), MC2 (middle), and ...
Figure 5: (a) CD spectra, (b) |gabs|, and (c) glum values of enantiomers of MC1 measured in dichloromethane a...
Catalytic asymmetric reactions of isocyanides for constructing non-central chirality
- Jia-Yu Liao
Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129
- ring were proven to be suitable substrates to react with tert-butyl isocyanoacetate, affording 3-heteroarylpyrroles 41 in 55–99% yield with 70–96% ee. In these cases, additional 2.0 equivalents of DBU were required to facilitate the conversion from the [3 + 2] cycloadducts to the final products
Graphical Abstract
Figure 1: a) Common types of chirality. b) Representative functional molecules bearing non-central chirality.
Scheme 1: Construction of planar chirality.
Scheme 2: Construction of axial chirality.
Scheme 3: Construction of inherent chirality.
Scheme 4: Construction of helical chirality.
Scheme 5: CPA-catalyzed enantioselective Groebke–Blackburn–Bienaymé reaction.
Scheme 6: Construction of axially chiral 3-arylpyrroles via de novo pyrrole formation.
Scheme 7: Synthesis of atropoisomeric 3-arylpyrroles via central-to-axial chirality transfer.
Scheme 8: Dynamic kinetic resolution of bridged biaryls with α-acidic isocyanides.
Scheme 9: Desymmetrization of prochiral compounds with α-acidic isocyanides.
Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles
- Vladimir G. Ilkin,
- Pavel S. Silaichev,
- Valeriy O. Filimonov,
- Tetyana V. Beryozkina,
- Margarita D. Likhacheva,
- Pavel A. Slepukhin,
- Wim Dehaen and
- Vasiliy A. Bakulev
Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104
- thioamides 1h,i,k,n,o,s,t,v,w,y,z (general procedure). A mixture of the corresponding thioacetamide (1.0 equiv), aldehyde (1.1–4.0 equiv) and DBU (0.1 equiv or 1.0 equiv for 1h,o) in ethanol was stirred for 2–23 h at room temperature. For thioamide 1i, the reaction time was 96 h at 80 °C. The formed
Graphical Abstract
Figure 1: Representatives of biologically active 1,2-thiazoles.
Scheme 1: Synthesis of 2,5-dihydro-1,2-thiazoles.
Scheme 2: Synthesis of 2,3-dihydro-N-sulfonyl-1,2-thiazoles 3. Conditions: aMethod A: thioamide 1 (1.0 equiv)...
Figure 2: Compound 3aa in thermal ellipsoids 50% probability.
Oxetanes: formation, reactivity and total syntheses of natural products
- Peter Gabko,
- Martin Kalník and
- Maroš Bella
Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101
Graphical Abstract
Figure 1: Bond lengths and bond angles in oxetane at 140 K [2].
Figure 2: Analogy of 3-substituted oxetanes to carbonyl and gem-dimethyl groups [12].
Figure 3: Use of oxetanes in drug design – selected examples.
Figure 4: Examples of oxetane-containing natural products.
Scheme 1: Synthetic strategies towards construction of the oxetane ring.
Scheme 2: Overview of intramolecular Williamson etherification and competing Grob fragmentation.
Scheme 3: Synthesis of spiro-oxetanes via 1,4-C–H insertion and Williamson etherification.
Scheme 4: Use of phenyl vinyl selenone in the synthesis of spirooxindole oxetanes.
Scheme 5: Synthesis of bicyclic 3,5-anhydrofuranoses via double epoxide opening/etherification.
Scheme 6: Preparation of spirooxetanes by cycloisomerisation via MHAT/RPC.
Scheme 7: Oxetane synthesis via alcohol C–H functionalisation.
Scheme 8: Access to oxetanes 38 from α-acetyloxy iodides.
Scheme 9: The kilogram-scale synthesis of oxetane intermediate 41.
Scheme 10: Overview of the intramolecular opening of 3-membered rings.
Scheme 11: Synthesis of 4,7-dioxatricyclo[3.2.1.03,6]octane skeletons.
Scheme 12: Silicon-directed electrophilic cyclisation of homoallylic alcohols.
Scheme 13: Hydrosilylation–iodocyclisation of homopropargylic alcohols.
Scheme 14: Cu-catalysed intramolecular O-vinylation of γ-bromohomoallylic alcohols.
Scheme 15: Cu-catalysed intramolecular cross-coupling of hydroxyvinylstannanes.
Scheme 16: Isomerisation of oxiranyl ethers containing weakly carbanion-stabilising groups.
Scheme 17: Cyclisation of diethyl haloalkoxymalonates.
Scheme 18: Synthesis of oxetanes through a 1,5-HAT/radical recombination sequence.
Scheme 19: General approach to oxetanes via [2 + 2] cycloadditions.
Scheme 20: Synthesis of tricyclic 4:4:4 oxetanes through a photochemical triple cascade reaction.
Scheme 21: Iridium-catalysed Paternò–Büchi reaction between α-ketoesters and simple alkenes.
Scheme 22: Three-step synthesis of spirocyclic oxetanes 83 via Paternò–Büchi reaction, nucleophilic ring openi...
Scheme 23: Enantioselective Paternò–Büchi reaction catalysed by a chiral iridium photocatalyst.
Scheme 24: Synthesis of polysubstituted oxetanes 92 via Cu(II)-mediated formal [2 + 2] cycloadditions.
Scheme 25: Synthesis of alkylideneoxetanes via NHC- and DBU-mediated formal [2 + 2] cycloadditions.
Scheme 26: Use of sulphur-stabilised carbanions in ring expansions.
Scheme 27: Synthesis of α,α-difluoro(arylthio)methyl oxetanes.
Scheme 28: Ring expansion in an industrial synthesis of PF-06878031.
Scheme 29: Ring contraction of triflated 2-hydroxy-γ-lactones.
Scheme 30: Ring contraction in an industrial synthesis of PF-06878031.
Scheme 31: Photochemical ring contraction of 2,5-dihydrofurans by aryldiazoacetic acid esters.
Scheme 32: Synthesis of 3-oxetanones via O-H insertion of carbenes.
Scheme 33: Synthesis of phosphonate oxetanones via gold-mediated alkyne oxidation/O–H insertion.
Scheme 34: Syntheses and common derivatisations of 3-oxetanone.
Scheme 35: SN1 substitution of 3-aryloxetan-3-ols by thiols and alcohols.
Scheme 36: Fe–Ni dual-catalytic olefin hydroarylation towards 3-alkyl-3-(hetero)aryloxetanes.
Scheme 37: Synthesis of 3-aryloxetan-3-carboxylic acids.
Scheme 38: Decarboxylative alkylation of 3-aryloxetan-3-carboxylic acids.
Scheme 39: Synthesis of 3-amino-3-aryloxetanes via photoredox/nickel cross-coupling catalysis.
Scheme 40: Intermolecular cross-selective [2 + 2] photocycloaddition towards spirooxetanes.
Scheme 41: Synthesis of 3-aryl-3-aminooxetanes via defluorosulphonylative coupling.
Scheme 42: Two-step synthesis of amide bioisosteres via benzotriazolyl Mannich adducts 170.
Scheme 43: Functionalisation of oxetanyl trichloroacetimidates 172.
Scheme 44: Synthesis of oxetane-amino esters 176.
Scheme 45: Tandem Friedel–Crafts alkylation/intramolecular ring opening of 3-aryloxetan-3-ols.
Scheme 46: Synthesis of polysubstituted furans and pyrroles.
Scheme 47: Synthesis of oxazolines and bisoxazolines.
Scheme 48: Tandem, one-pot syntheses of various polycyclic heterocycles.
Scheme 49: Synthesis of 1,2-dihydroquinolines via skeletal reorganisation of oxetanes.
Scheme 50: Synthesis of benzoindolines and 2,3-dihydrobenzofurans and their derivatisations.
Scheme 51: Synthesis of polysubstituted 1,4-dioxanes.
Scheme 52: Preparation of various lactones via ring opening of oxetane-carboxylic acids 219.
Scheme 53: Tsuji-Trost allylation/ring opening of 3-aminooxetanes.
Scheme 54: Arylative skeletal rearrangement of 3-vinyloxetan-3-ols to 2,5-dihydrofurans.
Scheme 55: Reductive opening of oxetanes using catalytic Mg–H species.
Scheme 56: Opening of oxetanes by silyl ketene acetals.
Scheme 57: Rhodium-catalysed hydroacylation of oxetanes.
Scheme 58: Generation of radicals from oxetanes mediated by a vitamin B12-derived cobalt catalyst.
Scheme 59: Reductive opening of oxetanes by B–Si frustrated Lewis pairs.
Scheme 60: Zirconocene-mediated reductive opening of oxetanes.
Scheme 61: Enantioselective syntheses of small and medium-size rings using chiral phosphoric acids.
Scheme 62: Asymmetric synthesis of 2,3-dihydrobenzo[b]oxepines catalysed by a chiral scandium complex.
Scheme 63: Enantioselective synthesis of 1,3-bromohydrins under a chiral squaramide catalysis.
Scheme 64: Enantioselective opening of 2-aryl-2-ethynyloxetanes by anilines.
Scheme 65: Ru-catalysed insertion of diazocarbonyls into oxetanes.
Scheme 66: Ring expansion of oxetanes by stabilised carbenes generated under blue light irradiation.
Scheme 67: Expansion of oxetanes via nickel-catalysed insertion of alkynyltrifluoroborates.
Scheme 68: Nickel-catalysed expansion of oxetanes into ε-caprolactones.
Scheme 69: Expansion of oxetanes via cobalt-catalysed carbonyl insertion.
Scheme 70: Gold-catalysed intramolecular 1,1-carboalkoxylation of oxetane-ynamides.
Scheme 71: Expansion of oxetanes by stabilised sulphoxonium ylides.
Scheme 72: Cu-catalysed ring expansion of 2-vinyloxetanes by diazoesters.
Scheme 73: Total synthesis of (+)-oxetin.
Scheme 74: Total synthesis of racemic oxetanocin A.
Scheme 75: Total synthesis of (−)-merrilactone A.
Scheme 76: Total synthesis of (+)-dictyoxetane.
Scheme 77: Total synthesis of ent-dichrocephone B.
Scheme 78: Total synthesis of (−)-mitrephorone A.
Scheme 79: Total synthesis of (−)-taxol.
Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes
- Bartłomiej Pigulski
Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99
- two azulene moieties (Scheme 19) [97]. Precursors 148 and 149 were annulated using DBU (1,8-diazabicyclo(5.4.0)undec-7-ene) in NMP (N-methyl-2-pyrrolidone) at 180 °C. The resulting PAHs 150 and 151 were isolated in relatively good yields (40% and 48%, respectively) and exhibited typical azulene-like
Graphical Abstract
Figure 1: a) Stone–Wales (red) and azulene (blue) defects in graphene; b) azulene and its selected resonance ...
Figure 2: Examples of azulene-embedded 2D allotropic forms of carbon: a) phagraphene and b) TPH-graphene.
Scheme 1: Synthesis of non-alternant isomers of pyrene (2 and 6) using dehydrogenation.
Scheme 2: Synthesis of non-alternant isomer 9 of benzo[a]pyrene and 14 of benzo[a]perylene using dehydrogenat...
Scheme 3: Synthesis of azulene-embedded isomers of benzo[a]pyrene (18 and 22) inspired by Ziegler–Hafner azul...
Figure 3: General strategies leading to azulene-embedded nanographenes: a) construction of azulene moiety in ...
Scheme 4: Synthesis of biradical PAHs possessing significant biradical character using oxidation of partially...
Scheme 5: Synthesis of dicyclohepta[ijkl,uvwx]rubicene (29) and its further modifications.
Scheme 6: Synthesis of warped PAHs with one embedded azulene subunit using Scholl-type oxidation.
Scheme 7: Synthesis of warped PAHs with two embedded azulene subunits using Scholl oxidation.
Scheme 8: Synthesis of azulene-embedded PAHs using [3 + 2] annulation accompanied by ring expansion.
Scheme 9: Synthesis of azulene-embedded isomers of linear acenes using [3 + 2] annulation accompanied by ring...
Scheme 10: Synthesis of azulene-embedded PAHs using intramolecular C–H arylation.
Scheme 11: Synthesis of azulene-embedded isomers of acenes using intramolecular C–H arylation.
Scheme 12: Synthesis of azulene-embedded PAHs using intramolecular condensations.
Scheme 13: Synthesis of azulene-embedded PAH 89 using palladium-catalysed [5 + 2] annulation.
Scheme 14: Synthesis of azulene-embedded PAHs using oxidation of substituents around the azulene core.
Scheme 15: Synthesis of azulene-embedded PAHs using the oxidation of reactive positions 1 and 3 of azulene sub...
Scheme 16: Synthesis of azulene-embedded PAHs using intramolecular C–H arylation.
Scheme 17: Synthesis of an azulene-embedded isomer of terylenebisimide using tandem Suzuki coupling and C–H ar...
Scheme 18: Synthesis of azulene embedded PAHs using a bismuth-catalyzed cyclization of alkenes.
Scheme 19: Synthesis of azulene-embedded nanographenes using intramolecular cyclization of alkynes.
Scheme 20: Synthesis of azulene-embedded graphene nanoribbons and azulene-embedded helicenes using annulation ...
Scheme 21: Synthesis of azulene-fused acenes.
Scheme 22: Synthesis of non-alternant isomer of perylene 172 using Yamamoto-type homocoupling.
Scheme 23: Synthesis of N- and BN-nanographenes with embedded azulene unit(s).
Scheme 24: On-surface synthesis of azulene-embedded nanographenes from benzenoid precursors via dehydrogenatio...
Scheme 25: On-surface synthesis of azulene-embedded nanographenes from benzenoid precursors.
Scheme 26: On-surface synthesis of azulene-embedded nanoribbons.
Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents
- Jiangfei Chen,
- Yi-Lin Qu,
- Ming Yuan,
- Xiang-Mei Wu,
- Heng-Pei Jiang,
- Ying Fu and
- Shengrong Guo
Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98
- heteroatom for the synthesis of functionalized oxindoles was also reported in 2013 [3]. In this study, DBU was employed as a ligand and TBHP as an oxidant. A series of ethers, including 1,2-dimethoxyethane, THF, 1,4-dioxane, tetrahydro-2H-pyran, 2,3-dihydrobenzofuran, tetrahydro-2H-thiopyran, and N
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.
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
- with a catalytic base has also been applied to prepare cinnamate esters. For example, Heller and co-workers (2021) synthesized the ester 141 catalyzed by DBU which functioned as a Brønsted base for the alcohol (Scheme 43A) [81]. Impressively, the method could be scaled up to a multigram scale
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.
Substituent effects in N-acetylated phenylazopyrazole photoswitches
- Radek Tovtik,
- Dennis Marzin,
- Pia Weigel,
- Stefano Crespi and
- Nadja A. Simeth
Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66
- further issue, we observed some instability at acidic pH during analysis. Thus, we tested the stability of NAc-PAP-H (1 mM, MeOH, ambient conditions, 2 h) at pH 2, 12, and in the presence of DBU (10−2 M) and found that the acetyl group was lost (cf. Supporting Information File 1, section 2.4). UV–vis
Graphical Abstract
Scheme 1: Reaction pathway for synthesizing NH-substituted, methylated-, and acetylated arylazopyrazoles. Con...
Figure 1: UV–vis absorption spectra of selected NAc-PAP derivatives in CH3CN. The strong π→π* can be observed...
Figure 2: A) Time-resolved UV–vis absorption spectra of NAc-PAP-CN upon 365 nm irradiation (12.5 µM in CH3CN,...
Figure 3: Hammett plot of NAc-PAP derivatives.
Figure 4: Eyring plots for NAc-PAP-CN and NAc-PAP-OMe.
Recent advances in the electrochemical synthesis of organophosphorus compounds
- Babak Kaboudin,
- Milad Behroozi,
- Sepideh Sadighi and
- Fatemeh Asgharzadeh
Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61
- ). Although using other solvents improved the solubility, it reduced the reaction yield. Ammonium thiocyanate is used as a sulfur source in the presence of DBU as a base and n-Bu4NBF4 as an electrolyte. When electron-donating groups were present at the C2-benzene ring, the reaction yield was higher than when
- the rings contained electron-withdrawing groups. It is suggested that the reaction proceeded via single-electron oxidation of thiocyanate at the anode. DBU was used in the reaction for a simple nucleophilic substitution of phosphonate with a cyanide group in the formed intermediate (Scheme 28). In
Graphical Abstract
Scheme 1: Electrosynthesis of phenanthridine phosphine oxides.
Scheme 2: Electrosynthesis of 1-aminoalkylphosphine oxides.
Scheme 3: Various electrochemical C–P coupling reactions.
Scheme 4: Electrochemical C–P coupling reaction of indolines.
Scheme 5: Electrochemical C–P coupling reaction of ferrocene.
Scheme 6: Electrochemical C–P coupling reaction of acridines with phosphites.
Scheme 7: Electrochemical C–P coupling reaction of alkenes.
Scheme 8: Electrochemical C–P coupling reaction of arenes in a flow system.
Scheme 9: Electrochemical C–P coupling reaction of heteroarenes.
Scheme 10: Electrochemical C–P coupling reaction of thiazoles.
Scheme 11: Electrochemical C–P coupling reaction of indole derivatives.
Scheme 12: Electrosynthesis of 1-amino phosphonates.
Scheme 13: Electrochemical C–P coupling reaction of aryl and vinyl bromides.
Scheme 14: Electrochemical C–P coupling reaction of phenylpyridine with dialkyl phosphonates in the presence o...
Scheme 15: Electrochemical P–C bond formation of amides.
Scheme 16: Electrochemical synthesis of α-hydroxy phosphine oxides.
Scheme 17: Electrochemical synthesis of π-conjugated phosphonium salts.
Scheme 18: Electrochemical phosphorylation of indoles.
Scheme 19: Electrochemical synthesis of phosphorylated propargyl alcohols.
Scheme 20: Electrochemical synthesis of phosphoramidates.
Scheme 21: Electrochemical reaction of carbazole with diphenylphosphine.
Scheme 22: Electrochemical P–N coupling of carbazole with phosphine oxides.
Scheme 23: Electrochemical P–N coupling of indoles with a trialkyl phosphite.
Scheme 24: Electrochemical synthesis of iminophosphoranes.
Scheme 25: Electrochemical P–O coupling of phenols with dialkyl phosphonate.
Scheme 26: Electrochemical P–O coupling of alcohols with diphenylphosphine.
Scheme 27: Electrochemical P–S coupling of thiols with dialkylphosphines.
Scheme 28: Electrochemical thiophosphorylation of indolizines.
Scheme 29: Electrosynthesis of S-heteroaryl phosphorothioates.
Scheme 30: Electrochemical phosphorylation reactions.
Scheme 31: Electrochemical P–Se formation.
Scheme 32: Electrochemical selenation/halogenation of alkynyl phosphonates.
Scheme 33: Electrochemical enantioselective aryl C–H bond activation.
Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex
- Maurizio Iannuzzi,
- Thomas Hohmann,
- Michael Dyrks,
- Kilian Haoues,
- Katarzyna Salamon-Krokosz and
- Beate Koksch
Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52
- , base, solvent, and reagent equivalents to optimize the alkylation reaction for both bromides 4 and 5 (Table 1 and Table 2). For Ni(II) complex of [2.3.5.6F]TfMePhe (6), firstly we screened different inorganic and organic bases (Table 1, entries 1–3) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was
- identified as optimal delivering a yield of alkylated complex of 60% (Table 1, entry 4). With DBU as base different solvents differing in polarity have been tested. At room temperature, acetonitrile proved best and increased the yield to 88% (Table 1, entry 11). Lowering the temperature to 0 °C led to a
- final yield of 94%. At these conditions (DBU, MeCN and 0 °C) the base and bromide equivalents were further modified but no further increase in yield could be achieved. Thus, 1.5 equiv DBU with 1.05 equiv alkyl bromide in MeCN at 0 °C have been identified as optimal conditions for the Ni complex
Graphical Abstract
Scheme 1: Previous work for obtaining different fluorinated amino acids and target fluorinated amino acids de...
Scheme 2: Synthesis of fluorinated aromatic amino acids 2 and 3.
Scheme 3: a) Gram-scale synthesis of fluorinated alkyl iodide precursor 10; b) Synthesis of trifluorinated le...
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
- ]. In some cases, the addition of a non-nucleophilic base is needed to neutralize the HCl generated during the reaction (Scheme 20). For example, Yu et al. demonstrated that the reaction yield could be significantly increased when the reaction was performed in the presence of one equivalent of DBU [62
- ]. They argued that organic bases such as DBU are superior than inorganic bases in improving the yields, probably because of the low solubility of the last ones in the reaction system. In the same way, other bases such as DABCO [64], DBU [66], and TMG (1,1,3,3-tetramethylguanidine) [65][67] were shown to
- (I)) by reducing the suitable salts (containing Au(III), Co(II), Fe(III), and Ni(II), respectively) at the beginning of the catalytic cycle. The metal in its reduced species (depicted in Scheme 23) activates the C–H bond of the alkyne. After this activation step, a weak base (like DBU, TMG, or even
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.
Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene
- Long K. San,
- Sebastian Balser,
- Brian J. Reeves,
- Tyler T. Clikeman,
- Yu-Sheng Chen,
- Steven H. Strauss and
- Olga V. Boltalina
Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39
- organic base such as tetramethylethylenediamine (TMEDA) or 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) [28]. Our initial attempt to apply this method was as follows: A reaction mixture of 9,10-ANTH(Br)2, 10 equiv BnFI, and 10 equiv DBU dissolved in acetone was illuminated with a blue LED for 20 h (see
Graphical Abstract
Scheme 1: List of reactions, experimental conditions and yields studied in this work.
Figure 1: Top: 379 MHz 19F NMR spectrum of 9,10-ANTH(BnF)2 in CDCl3. Bottom: absorption (aerobic, solid line)...
Figure 2: Top: X-ray structure of 9,10-ANTH(BnF)2, thermal ellipsoids 50% probability. Bottom: a view down th...
Figure 3: Absorption spectra of ANTH and 9,10-ANTH(BnF)2 in CH2Cl2 recorded over the period of 53 days in air...
Figure 4: Direct analysis in real time (DART) positive ion mass spectrum of the photoirradiated 9,10-ANTH(BnF)...
Figure 5: The % remaining of ANTH and 9,10-ANTH(BnF)2 dissolved in CDCl3 upon irradiation. Resonances δ = 7.4...
Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane
- Zahra Noori,
- Miquel Solà,
- Clara Viñas,
- Francesc Teixidor and
- Jordi Poater
Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29
- -1,3-dimethylimidazolinium hexafluorophosphate (ADMP) in the presence of DBU in acetonitrile. This one-pot process enables sequential diazotization and cyclization, leading to the formation of two or three C–N bonds under extremely mild conditions, with excellent tolerance for various functional groups
Graphical Abstract
Figure 1: Series o-carborane-fused pyrazoles under analysis.
Figure 2: Bond lengths (in Å) of systems under analysis (top row) and reference systems (second and third row...
Figure 3: Series of reference systems for the o-carborane-fused pyrazoles under analysis.
Figure 4: NICS (in ppm) of the boron cages (computed for the top 5-membered ring, center and bottom 5-membere...
Figure 5: AICD plots of systems under analysis from the fusion of o-carborane and pyrazole/pyrazoline and ref...
Figure 6: Current density maps (all-electron contributions) for a perpendicular magnetic field over a plane 1...
The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation
- Rituparna Das and
- Balaram Mukhopadhyay
Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27
- in machine-assisted oligosaccharide synthesis. 4-Acetoxy-2,2-dimethylbutanoyl (ADMB) esters were reported by Ensley and co-workers [108] having similar properties with the pivalate group. The facile removal of the C-2-ADMB group with a catalytic quantity of diazabicycloundecane (DBU) in methanol at
Graphical Abstract
Scheme 1: Continuum in the mechanistic pathway of glycosylation [32] reactions ranging between SN2 and SN1.
Scheme 2: Formation of 1,2-trans glycosides by neighbouring group participation with acyl protection in C-2 p...
Scheme 3: Solvent-free activation [92] of disarmed per-acetylated (15) and per-benzoylated (18) glycosyl donors.
Scheme 4: Synthesis of donor 2-(2,2,2-trichloroethoxy)glucopyrano-[2,1-d]-2-oxazoline 22 [94] and regioselective ...
Scheme 5: The use of levulinoyl protection for an orthogonal glycosylation reaction.
Figure 1: The derivatives 32–36 of the pivaloyl group.
Scheme 6: Benzyl and cyanopivalolyl ester-protected hexarhamnoside derivative 37 and its global deprotection ...
Scheme 7: Orthogonal chloroacetyl group deprotection in oligosaccharide synthesis [113].
Figure 2: The derivatives of the chloroacetyl group: CAMB protection (41) [123], CAEB protection (42) [124], POMB prote...
Scheme 8: Use of the (2-nitrophenyl)acetyl protecting group [126] as the neighbouring group protecting group at th...
Scheme 9: Neighbouring group participation protocol by the BnPAc protecting group [128] in the C-2 position.
Scheme 10: Glycosylation reaction with O-PhCar (54) and O-Poc (55) donors showing high β-selectivity [133].
Scheme 11: Neighbouring group participation rendered by an N-benzylcarbamoyl (BnCar) group [137] at the C-2 positio...
Scheme 12: Stereoselectivity obtained from glycosylation [138] with 2-O-(o-trifluoromethylbenzenesulfonyl)-protecte...
Scheme 13: (a) Plausible mechanistic pathway for glycosylation with C-2 DMTM protection [139] and (b) example of a ...
Scheme 14: Glycosylation reactions employing MOM 78, BOM 81, and NAPOM 83-protected thioglycoside donors. Reag...
Scheme 15: Plausible mechanistic pathway for alkoxymethyl-protected glycosyl donors. Path A. Expected product ...
Scheme 16: Plausible mechanistic pathway for alkoxymethyl-protected glycosyl donors [147].
Scheme 17: A. Formation of α-glycosides and B formation of β-glycosides by using chiral auxiliary neighbouring...
Scheme 18: Bimodal participation of 2-O-(o-tosylamido)benzyl (TAB) protecting group to form both α and β-isome...
Scheme 19: (a) 1,2-trans-Directing nature using C-2 cyanomethyl protection and (b) the effect of acceptors and...
Scheme 20: 1,3-Remote assistance by C-3-ester protection for gluco- and galactopyranosides to form 1,2-cis gly...
Scheme 21: 1,6-Remote assistance by C-6-ester protection for gluco- and galactopyranosides to form 1,2-cis gly...
Scheme 22: 1,4-Remote assistance by C-4-ester protection for galactopyranosides to form 1,2-cis glycosidic pro...
Scheme 23: Different products obtained on activation of axial 3-O and equatorial 3-O ester protected glycoside...
Scheme 24: The role of 3-O-protection on the stereochemistry of the produced glycoside [191].
Scheme 25: The role of 4-O-protection on the stereochemistry of the produced glycosides.
Scheme 26: Formation and subsequent stability of the bicyclic oxocarbenium intermediate formed due to remote p...
Scheme 27: The role a C-6 p-nitrobenzoyl group on the stereochemistry of the glycosylated product [196].
Scheme 28: Difference in stereoselectivity obtained in glycosylation reactions by replacing non-participating ...
Scheme 29: The role of electron-withdrawing and electron-donating substituents on the C-4 acetyl group in glyc...
Scheme 30: Effect of the introduction of a methyl group in the C-4 position on the glycosylation with more rea...
Figure 3: Remote group participation effect exhibited by the 2,2-dimethyl-2-(o-nitrophenyl)acetyl (DMNPA) pro...
Scheme 31: The different stereoselectivities obtained by Pic and Pico donors on being activated by DMTST.
Figure 4: Hydrogen bond-mediated aglycon delivery (HAD) in glycosylation reactions for 1,2-cis 198a and 1,2-t...
Scheme 32: The role of different acceptor with 6-O-Pic-protected glycosyl donors.
Scheme 33: The role of the remote C-3 protection on various 4,6-O-benzylidene-protected mannosyl donors affect...
Scheme 34: The dual contribution of the DTBS group in glycosylation reactions [246,247].
Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles
- Zi-Ying Xiao,
- Jing Sun and
- Chao-Guo Yan
Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21
- such as DABCO, DBU, triethylamine, and K2CO3 also resulted in the significant reduction of the yields. Therefore, the reaction of MBH nitrile of isatins and arylamines can be simply carried out in toluene at room temperature in the presence of a catalytic amount of DMAP. With the optimized reaction
Graphical Abstract
Scheme 1: Reaction of arylamines and MBH carbonates of isatins. Reaction conditions: MBH carbonate of isatin ...
Scheme 2: Reaction of arylamines and MBH maleimides of isatins. Reaction conditions: MBH maleimide of isatin ...
Figure 1: Single crystal structure of compound 5a.
Figure 2: Single crystal structure of compound 5j.
Scheme 3: Reactions of MBH carbonates of isatins and triphenylphosphine. Reaction conditions: MBH carbonate o...
Figure 3: Single crystal structure of compound 6e.
Figure 4: Single crystal structure of compound 7a.
Figure 5: Single crystal structure of compound 8a.
Scheme 4: Proposed reaction mechanism for the various compounds.
Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling
- John M. Halford-McGuff,
- Thomas M. Richardson,
- Aidan P. McKay,
- Frederik Peschke,
- Glenn A. Burley and
- Allan J. B. Watson
Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265
- equiv), DMF, air, rt, 2 h. (iv) Pd(dtbpf)Cl2 (10 mol %), 2-acetylthiophen-3-ylboronic acid (1.2 equiv), K3PO4 (2.0 equiv), iPrOH/H2O 3:4, N2, 85 °C, 16 h. (v) Pd(dtbpf)Cl2 (2.0 mol %), 1-naphthylzinc bromide (1.2 equiv), THF, N2, 45 °C, 16 h. (vi) Cu(OAc)2·H2O (30 mol %), B(OH)3 (2.0 equiv), DBU (2.0
Graphical Abstract
Scheme 1: The CuAAC reaction and installation of functional groups for product diversification.
Scheme 2: Scope of germanyl acetylene CuAAC. Alkyne (1.0 equiv), azide (1.1 equiv), CuSO4·5H2O (5.0 mol %), N...
Scheme 3: (a) Application of Ge-alkyne CuAAC to functional molecules. (b) Functionalisation of germylated tri...
Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy
- Robin Schulte,
- Dustin Schade,
- Thomas Paululat,
- Till J. B. Zähringer,
- Christoph Kerzig and
- Heiko Ihmels
Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254
- section and complete set of NMR spectra. Funding Financial support was provided by the University of Siegen. R.S. is grateful to the House of Young Talents (University of Siegen) and the Stiftung Nagelschneider for the Ph.D. fellowships. T.J.B.Z. thanks the Deutsche Bundesstiftung Umwelt (DBU) for a Ph.D
Graphical Abstract
Scheme 1: Photoinduced [2 + 2]-cycloaddition–cycloreversion cycle of norbornadiene (1a) and quadricyclane (2a...
Figure 1: Representative bis- and tris-norbornadienyl-substituted benzene derivatives.
Scheme 2: Synthesis of alkynyl-arene-linked norbornadienes 1h–n by Sonogashira–Hagihara coupling reactions.
Scheme 3: Photoisomerization of norbornadiene derivatives 1h–l,n (20 µM) to quadricyclanes 2h–l,n in cyclohex...
Figure 2: Photometric monitoring of the irradiation of 1h (A), 1i (B), 1j (C), 1k (D), 1l (E), and 1n (F); λex...
Scheme 4: Triplet-sensitized photoisomerization of norbornadiene 1o to quadricyclane 2o.
Figure 3: Photometric monitoring of the irradiation of 1i (A) and 1l (B) in the presence of [Ru(phen)3](PF6)2...
