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Search for "tert-butyl" in Full Text gives 700 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling
- Guoling Huang,
- Huarui Zhu,
- Shuting Zhou,
- Wanlin Zheng,
- Fangpeng Liang,
- Zhibo Zhao,
- Yifei Chen and
- Xunbo Lu
Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9
- efficiently even with secondary hydroxy groups. The method also accommodated sterically hindered and functionalized alcohols. tert-Butylmethanol in which the hydroxy group is attached to a methylene adjacent to a bulky tert-butyl group, gave the desired product 3v’ in 91% yield, while a halogenated alcohol
Graphical Abstract
Figure 1: Representative molecules containing a sulfilimine moiety.
Scheme 1: PIDA-mediated approach versus the present NBS-mediated approach to sulfinimidate esters.
Scheme 2: Substrate scope of sulfenamides derived from various thiophenols and thiols. Reaction conditions: s...
Scheme 3: Substrate scope of sulfenamides derived from various amides. Reaction conditions: sulfenamide 1 (0....
Scheme 4: Substrate scope of reactions between sulfenamides 1a and various alcohols. Reaction conditions: asu...
Scheme 5: Scale-up synthesis, late-stage derivatization, and substitution of diastereomeric sulfinimidate est...
Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts
- Kadri Kriis,
- Harry Martõnov,
- Annette Miller,
- Mia Peterson,
- Ivar Järving and
- Tõnis Kanger
Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8
- with the steric effect of the tert-butyl group of the catalyst, is responsible for the high stereoselectivity of the reaction. Keywords: aromatic imine; asymmetric catalysis; Mannich reaction; noncovalent interactions; organocatalysis; Introduction The Mannich reaction, i.e., the addition of an
Graphical Abstract
Scheme 1: The catalytic Mannich reaction under study.
Figure 1: Screened catalysts.
Figure 2: Model for the interaction of the catalyst with the imine.
Figure 3: Substrate scope of the asymmetric Mannich reaction.
Total synthesis of natural products based on hydrogenation of aromatic rings
- Haoxiang Wu and
- Xiangbing Qi
Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4
- , constructing the [2.2.2]-bridged ring within the (+)-nominine followed by protection of the primary alcohol as mesylate. Using lithium bromide as the bromine source, an SN2 reaction was performed, and the allylic position was oxidized with tert-butyl peroxide and selenium dioxide to generate the enone 104
- spontaneously underwent an intramolecular cycloaddition to yield the highly rigid [2.2.2]-bridged ring skeleton in ketone 116. Finally, nominine was generated via a two-step sequence comprising a Wittig reaction followed by tert-butyl peroxide/selenium dioxide-mediated allylic oxidation, thereby completing
Graphical Abstract
Scheme 1: The association between dearomatization and natural product synthesis.
Scheme 2: Key challenges in hydrogenation of aromatic rings.
Scheme 3: Hydrogenation of heterocyclic aromatic rings.
Scheme 4: Hydrogenation of the carbocyclic aromatic rings.
Scheme 5: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 6: Hydrogenation of the heterocycle part in bicyclic aromatic rings.
Scheme 7: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 8: Hydrogenation of benzofuran, indole, and their analogues.
Scheme 9: Total synthesis of (±)-keramaphidin B by Baldwin and co-workers.
Scheme 10: Total synthesis of (±)-LSD by Vollhardt and co-workers.
Scheme 11: Total synthesis of (±)-dihydrolysergic acid by Boger and co-workers.
Scheme 12: Total synthesis of (±)-lysergic acid by Smith and co-workers.
Scheme 13: Hydrogenation of (−)-tabersonine to (−)-decahydrotabersonine by Catherine Dacquet and co-workers.
Scheme 14: Total synthesis of (±)-nominine by Natsume and co-workers.
Scheme 15: Total synthesis of (+)-nominine by Gin and co-workers.
Scheme 16: Total synthesis of (±)-lemonomycinone and (±)-renieramycin by Magnus.
Scheme 17: Total synthesis of GB13 by Sarpong and co-workers.
Scheme 18: Total synthesis of GB13 by Shenvi and co-workers.
Scheme 19: Total synthesis of (±)-corynoxine and (±)-corynoxine B by Xia and co-workers.
Scheme 20: Total synthesis of (+)-serratezomine E and the putative structure of huperzine N by Bonjoch and co-...
Scheme 21: Total synthesis of (±)-serralongamine A and the revised structure of huperzine N and N-epi-huperzin...
Scheme 22: Early attempts to indenopiperidine core.
Scheme 23: Homogeneous hydrogenation and completion of the synthesis.
Scheme 24: Total synthesis of jorunnamycin A and jorumycin by Stoltz and co-workers.
Scheme 25: Early attempt towards (−)-finerenone by Aggarwal and co-workers.
Scheme 26: Enantioselective synthesis towards (−)-finerenone.
Scheme 27: Total synthesis of (+)-N-methylaspidospermidine by Smith, Grigolo and co-workers.
Scheme 28: Dearomatization approach towards matrine-type alkaloids.
Scheme 29: Asymmetric total synthesis to (−)-senepodine F via an asymmetric hydrogenation of pyridine.
Scheme 30: Selective hydrogenation of indole derivatives and application.
Scheme 31: Synthetic approaches to the oxindole alkaloids by Qi and co-workers.
Scheme 32: Total synthesis of annotinolide B by Smith and co-workers.
Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review
- Daniel S. Müller
Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1
- alkenyl chloride 156 was isolated only in trace amounts, alongside isomerized alkene 157 and dichloride 158. Notably, only the sterically hindered tert-butyl-substituted alkyne afforded the desired product 155 in high yields, whereas hydrochlorination of 4-octyne proved inefficient to deliver compound 159
- aliphatic carbocations (Scheme 40A) [142]. Treatment of tert-butyl chloride (215) with alkyne 3 in the presence of ZnCl2 furnished alkenyl chlorides 155 and 9, along with considerable amounts of polymeric byproducts [93][143]. Compound 155 was obtained with excellent stereoselectivity (>98:2 E/Z
- , aligned with the axis of the vacant orbital. In the case depicted in Scheme 40B, the face syn to the hydrogen is significantly more accessible than the face syn to the bulky tert-butyl group, accounting for the high E-selectivity observed. In contrast, alkyl groups with reduced steric demand led to
Graphical Abstract
Figure 1: Representative alkenyl chloride motifs in natural products. References: Pinnaic acid [8], haterumalide ...
Figure 2: Representative alkenyl chloride motifs in pharmaceuticals and pesticides. References: clomifene [25], e...
Figure 3: Graphical overview of previously published reviews addressing the synthesis of alkenyl chlorides.
Figure 4: Classification of synthetic approaches to alkenyl chlorides.
Scheme 1: Early works by Friedel, Henry, and Favorsky.
Scheme 2: Product distribution obtained by H NMR integration of crude compound as observed by Kagan and co-wo...
Scheme 3: Side reactions observed for the reaction of 14 with PCl5.
Scheme 4: Only compounds 15 and 18 were observed in the presence of Hünig’s base.
Scheme 5: Efficient synthesis of dichloride 15 at low temperatures.
Scheme 6: Various syntheses of alkenyl chlorides on larger scale.
Scheme 7: Scope of the reaction of ketones with PCl5 in boiling cyclohexane.
Scheme 8: Side reactions occur when using excess amounts of PCl5.
Scheme 9: Formation of versatile β-chlorovinyl ketones.
Scheme 10: Mixture of PCl5 and PCl3 used for the synthesis of 49.
Scheme 11: Catechol–PCl3 reagents for the synthesis of alkenyl chlorides.
Scheme 12: (PhO)3P–halogen-based reagents for the synthesis of alkenyl halides.
Scheme 13: Preparation of alkenyl chlorides from alkenyl phosphates.
Scheme 14: Preparation of alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 15: Preparation of electron-rich alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 16: Cu-promoted synthesis of alkenyl chlorides from ketones and POCl3.
Figure 5: GC yield of 9 depending on time and reaction temperature.
Figure 6: Broken reaction flask after attempts to clean the polymerized residue.
Figure 7: GC yield of 9 depending on the amount of CuCl and time.
Scheme 17: Treatment of 4-chromanones with PCl3.
Scheme 18: Synthesis of alkenyl chlorides from the reaction of ketones with acyl chlorides.
Scheme 19: ZnCl2-promoted alkenyl chloride synthesis.
Scheme 20: Regeneration of acid chlorides by triphosgene.
Scheme 21: Alkenyl chlorides from ketones and triphosgene.
Scheme 22: Various substitution reactions.
Scheme 23: Vinylic Finkelstein reactions reported by Evano and co-workers.
Scheme 24: Challenge of selective monohydrochlorination of alkynes.
Scheme 25: Sterically encumbered internal alkynes furnish the hydrochlorination products in high yield.
Scheme 26: Recent work by Kropp with HCl absorbed on alumina.
Scheme 27: High selectivities for monhydrochlorination with nitromethane/acetic acid as solvent.
Figure 8: Functionalized alkynes which typically afford the monhydrochlorinated products.
Scheme 28: Related chorosulfonylation and chloroamination reactions.
Scheme 29: Reaction of organometallic reagents with chlorine electrophiles.
Scheme 30: Elimination reactions of dichlorides to furnish alkenyl chlorides.
Scheme 31: Elimination reactions of allyl chloride 182 to furnish alkenyl chloride 183.
Scheme 32: Detailed studies by Schlosser on the elimination of dichloro compounds.
Scheme 33: Stereoselective variation caused by change of solvent.
Scheme 34: Elimination of gem-dichloride 189 to afford alkene 190.
Scheme 35: Oxidation of enones to dichlorides and in situ elimination thereof.
Scheme 36: Oxidation of allylic alcohols to dichlorides and in situ elimination thereof.
Scheme 37: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 38: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 39: Fluorine–chlorine exchange followed by elimination.
Scheme 40: Intercepting cations with alkynes and trapping of the alkenyl cation intermediate with chloride.
Scheme 41: Investigations by Mayr and co-workers.
Scheme 42: In situ activation of benzyl alcohol 230 with BCl3.
Scheme 43: In situ activation of benzylic alcohols with TiCl4.
Scheme 44: In situ activation of benzylic alcohols with FeCl3.
Scheme 45: In situ activation of benzylic alcohols with FeCl3.
Scheme 46: In situ activation of aliphatic chlorides and alcohols with ZnCl2, InCl3, and FeCl3.
Scheme 47: In situ generation of benzylic cations and trapping thereof with alkynes.
Scheme 48: Intramolecular trapping reactions affording alkenyl halides.
Scheme 49: Intramolecular trapping reactions affording alkenyl chlorides.
Scheme 50: Intramolecular trapping reactions of oxonium and iminium ions affording alkenyl chlorides.
Scheme 51: Palladium and nickel-catalyzed coupling reactions to afford alkenyl chlorides.
Scheme 52: Rhodium-catalyzed couplings of 1,2-trans-dichloroethene with arylboronic esters.
Scheme 53: First report on monoselective coupling reactions for 1,1-dichloroalkenes.
Scheme 54: Negishi’s and Barluenga’s contributions.
Scheme 55: First mechanistic investigation by Johnson and co-workers.
Scheme 56: First successful cross-metathesis with choroalkene 260.
Scheme 57: Subsequent studies by Johnson.
Scheme 58: Hoveyda and Schrock’s work on stereoretentive cross-metathesis with molybdenum-based catalysts.
Scheme 59: Related work with (Z)-dichloroethene.
Scheme 60: Further ligand refinement and traceless protection of functional groups with HBpin.
Scheme 61: Alkenyl chloride synthesis by Wittig reaction.
Scheme 62: Alkenyl chloride synthesis by Julia olefination.
Scheme 63: Alkenyl chloride synthesis by reaction of ketones with Mg/TiCl4 mixture.
Scheme 64: Frequently used allylic substitution reactions which lead to alkenyl chlorides.
Scheme 65: Enantioselective allylic substitutions.
Scheme 66: Synthesis of alkenyl chlorides bearing an electron-withdrawing group.
Scheme 67: Synthesis of α-nitroalkenyl chlorides from aldehydes.
Scheme 68: Synthesis of alkenyl chlorides via elimination of an in situ generated geminal dihalide.
Scheme 69: Carbenoid approach reported by Pace.
Scheme 70: Carbenoid approach reported by Pace.
Scheme 71: Ring opening of cyclopropenes in the presence of MgCl2.
Scheme 72: Electrophilic chlorination of alkenyl MIDA boronates to Z- or E-alkenyl chlorides.
Scheme 73: Hydroalumination and hydroboration of alkynyl chlorides.
Scheme 74: Carbolithiation of chloroalkynes.
Scheme 75: Chlorination of enamine 420.
Scheme 76: Alkyne synthesis by elimination of alkenyl chlorides.
Scheme 77: Reductive lithiation of akenyl chlorides.
Scheme 78: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 79: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 80: Addition–elimination reaction of alkenyl chloride 9 with organolithium reagents.
Scheme 81: C–H insertions of lithiumcarbenoids.
Scheme 82: Pd-catalyzed coupling reactions with alkenyl chlorides as coupling partner.
Scheme 83: Ni-catalyzed coupling of alkenylcopper reagent with alkenyl chloride 183.
Scheme 84: Ni-catalyzed coupling of heterocycle 472 with alkenyl chloride 473.
Scheme 85: Synthesis of α-chloroketones by oxidation of alkenyl chlorides.
Scheme 86: Tetrahalogenoferrate(III)-promoted oxidation of alkenyl chlorides.
Scheme 87: Chlorine–deuterium exchange promoted by a palladium catalyst.
Scheme 88: Reaction of alkenyl chlorides with thiols in the presence of AIBN (azobisisobutyronitrile).
Scheme 89: Chloroalkene annulation.
One-pot synthesis of ethylmaltol from maltol
- Immanuel Plangger,
- Marcel Jenny,
- Gregor Plangger and
- Thomas Magauer
Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212
- adjustment through an Achmatowicz rearrangement [8] initiated by either anodic oxidation [7][9][10], chlorine gas [11][12], or tert-butyl hypochlorite [13] provides pyran-3-ones. Further oxidation and acid- or heat-induced rearrangement furnishes ethylmaltol (1). Of note, some of these procedures allow for
- aqueous hydrochloric acid in a one-pot protocol. To our surprise, this consistently resulted in a 1:1 mixture of ethylmaltol (1) and maltol (2), each isolated in 30% yield. Assuming insufficient silyl stability during the methylation step, we opted to investigate the bulkier tert-butyl(dimethyl)silyl (TBS
- ) group. Protection of maltol (2) with tert-butyl(dimethyl)silyl chloride (TBSCl) afforded silyl ether 8e in 99% (Table 2, entry 5). Indeed, methylation of the lithium dienolate of 8e with methyl iodide at 0 °C afforded TBS-protected ethylmaltol (9e) in 64% with no trace of maltol (2). Subsequent
Graphical Abstract
Scheme 1: Importance and synthetic approaches to ethylmaltol (1). (a) Ethylmaltol (1) is widely used as a fla...
Scheme 2: Optimized one-pot procedure to access ethylmaltol (1) via a transient protecting group strategy.
Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives
- Loris Geminiani,
- Kathrin Junge,
- Matthias Beller and
- Jean-François Soulé
Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170
- were consumed, various impurities, including biphenyls, diarylamines, aniline, and toluidine, were formed in varying amounts. Since a final dehydrogenation step is required to complete the reaction, the experiment was repeated with various oxidants tested as additives. The use of di-tert-butyl peroxide
Graphical Abstract
Figure 1: General overview of azobenzene chemistry. a) Selected examples and photoisomerization of azobenzene...
Scheme 1: Scope of aryl bromides in palladium-catalyzed dehydrogenative C–N coupling with phenylhydrazine (1a...
Scheme 2: Scope of arylhydrazines in palladium-catalyzed dehydrogenative C–N coupling with 2-bromotoluene (2a...
Scheme 3: Application to the synthesis of tetra-, tri or di-ortho-substituted azobenzenes via palladium-catal...
Figure 2: a) Proposed catalytic cycle for the one-pot palladium-catalyzed dehydrogenative C–N coupling for th...
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
- ), tert-butyl isocyanide (3a), and TMSN3 (4) in 2 mL of MeOH. After heating the reaction mixture at 40 °C for 12 h, the solvent was removed and changed to 2 mL of MeCN followed by heating at 130 °C for 2 h (Scheme 3A). However, no desired product was detected in the reaction mixture. The functional groups
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
- reaction also showed high compatibility with 2-naphthyl (15h), 2-thiophenyl (15i), ferrocenyl (15j), cyclohexenyl (15k) and tert-butyl (15l) incorporated at the ethynyl moiety. According to the results of control experiments, a plausible mechanism was presented. Firstly, one-electron oxidation of 14a
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
- versatile scaffold for bioactive molecules) with up to 99% yield and 96% ee were prepared (Scheme 69). The large electron-donating groups of 3,5-di-tert-butyl-4-methoxyphenyl (DTBM) improved the activities of the CuI–thiophene-2-carboxylate catalyst (CuTc) while the use of (R)-DTBM-GarPhos as the chiral
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®.
α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions
- Vladyslav O. Honcharov,
- Yana I. Sakhno,
- Olena H. Shvets,
- Vyacheslav E. Saraev,
- Svitlana V. Shishkina,
- Tetyana V. Shcherbakova and
- Valentyn A. Chebanov
Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157
- library of bis- and tetraamides was synthesized by the Ugi reaction with α-ketoglutaric acid, tert-butyl isocyanide, aromatic aldehydes, and aromatic amines. When o-azidoanilines were used, azidated peptidomimetics were obtained, the post-cyclization of which by the aza-Wittig reaction yielded a series of
- -ketoglutaric acid in the four-component Ugi reaction with equimolar amounts of the reagents. It was found that stirring of aromatic aldehydes 2a–d, aromatic amines 3a–d, KGA (1) and tert-butyl isocyanide (4) (in a 1:1:1:1 molar ratio) in methanol for 24 hours at 45 °C resulted in the formation of 5-((aryl)(1
- procedures can be found in Supporting Information File 1). Since α-ketoglutaric acid is dibasic, increasing the stoichiometric amounts of the starting materials enables the Ugi reaction involving two carboxyl groups. Thus, mixing KGA (1), 4-chlorobenzaldehyde (2a), 4-chloroaniline (3a), and tert-butyl
Graphical Abstract
Figure 1: Some biologically active quinoxalinone derivatives.
Scheme 1: Known multicomponent reactions of KGA.
Scheme 2: Ugi reaction involving KGA.
Scheme 3: Tandem Ugi/aza-Wittig combination involving KGA.
Figure 2: Molecular structure of 3-(4-(2-(tert-butylamino)-1-(4-methoxyphenyl)-2-oxoethyl)-5,7-dimethyl-3-oxo...
Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis
- Rasma Kroņkalne,
- Rūdolfs Beļaunieks,
- Armands Sebris,
- Anatoly Mishnev and
- Māris Turks
Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154
- it improves lipophilicity, oral absorption and biological activity [25]. Results and Discussion Arylation of aliphatic chain-containing propargylsilanes We started our investigation with the arylation of aliphatic chain-containing propargylsilanes. The starting material – tert-butyl(hept-1-yn-3-yl
- formation. Its silylated version (7, where R = COOSi(Me)3) only resulted in starting material degradation. Interestingly, tert-butyl ester 7e (R = COOt-Bu) provided the desired arylated lactone 8t, along with the protodecupration product 13, which was formed in excess under the standard arylation conditions
- an internal nucleophile (O-, N-) and reductive elimination affords the arylated product 8 and regenerates the Cu(I) catalyst. The added base (B:) traps the H+, generated in this catalytic cycle. In the case of tert-butyl esters (7: R = COOt-Bu) an equivalent of isobutylene gas is released as a side
Graphical Abstract
Scheme 1: Alkyne arylation with diaryl-λ3-iodanes in the context of 1,2-silyl shift and potential cyclization....
Scheme 2: Competing mechanistic pathways for diene 10 and indene 11 formation.
Scheme 3: Reaction scope for the synthesis of arylated tetrahydrofurans 8. Conditions: All reactions were per...
Scheme 4: Synthesis of lactone and pyrrolidine derivatives. Conditions: ac7e = 0.1 mmol/mL. bReaction conditi...
Scheme 5: Proposed arylation–heterocyclization mechanism for internal nucleophile-containing silanes 7.
Scheme 6: Arylation of C5-chain containing acylamides 16a–c. aThe reaction was performed under modified condi...
Photochemical reduction of acylimidazolium salts
- Michael Jakob,
- Nick Bechler,
- Hassan Abdelwahab,
- Fabian Weber,
- Janos Wasternack,
- Leonardo Kleebauer,
- Jan P. Götze and
- Matthew N. Hopkinson
Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153
- = 4,4′-di-tert-butyl-2,2′-dipyridine) as a photocatalyst and the simple tertiary amine diisopropylethylamine (DIPEA, 5 equiv) in MeCN (0.05 M). After 24 h under irradiation with light from blue LEDs (λmax = 440 nm), the crude mixture was concentrated under reduced pressure and analyzed by 1H NMR
Graphical Abstract
Figure 1: (a) Combining N-heterocyclic carbene (NHC) organocatalysis with photoredox catalysis for radical–ra...
Figure 2: Initial test reaction employing [Ir(dF(CF3)ppy)2(dtbpy)]PF6 as a photocatalyst in the presence of D...
Scheme 1: Plausible mechanism for the photocatalytic reduction of benzoylimidazolium salt 1 with DIPEA. [PC] ...
Scheme 2: Plausible mechanism for the photocatalyst-free reduction of benzoylimidazolium salt 1 into O-benzoy...
Figure 3: Reduction of 2-benzoylimidazolium triflate (1) under photocatalyst-free conditions monitored over 4...
Scheme 3: (a) Reduction of 2-benzoylimidazolium triflate (1) under photocatalyst-free conditions with DIPEA a...
Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction
- Pricilla Matseketsa,
- Margret Kumbirayi Ruwimbo Pagare and
- Tendai Gadzikwa
Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144
- functionalized MOFs to the Knoevenagel condensation reaction. A well-defined MOF material composed of both amine- and hydroxy-bearing linkers was reacted with a series of aliphatic isocyanates (isopropyl, tert-butyl, n-hexyl, and tetradecyl) and, incongruously, was found to preferentially react at the hydroxy
- whose pores are uniformly decorated with different lipophilic groups (Figure 2A). Using this strategy, we quantitatively functionalized the –OH groups of KSU-1 with isopropyl and tert-butyl isocyanate. While primary isocyanates were less selective, starting to react at the amines before the hydroxy
- respective isocyanate in acetonitrile at 80 °C; KSU-1 reacted with isopropyl, tert-butyl, n-hexyl, and tetradecyl isocyanate to generate KSU-1iPr and KSU-1t-Bu, KSU-1n-Hex, and KSU-1C14, respectively. Successful post synthetic reaction was observed by proton nuclear magnetic resonance (1H NMR) spectroscopy
Graphical Abstract
Figure 1: Schematic representation of the modulation of MOF pore environments. A) de novo synthesis of severa...
Figure 2: A) Schematic representation of the reaction of KSU-1 with aliphatic isocyanates and the estimated c...
Scheme 1: Probable mechanisms for the Knoevenegel condensation reaction between benzaldehyde and malononitril...
Figure 3: A) Schematic representation of the reaction between benzaldehyde and malononitrile to form benzylid...
Figure 4: Graphical representation of the Knoevenagel catalysis results. A) Comparison of the reaction in tol...
Figure 5: Left: comparison of BMN and HPMM protons in 1H NMR spectra. Note that the peaks corresponding to HP...
Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp2)–C(sp2) bond scission of styrenes
- Prafull A. Jagtap,
- Manish M. Petkar,
- Vaishnavi R. Sawant and
- Bhalchandra M. Bhanage
Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142
- , resulting in the formation of both 3r and 3r′, which were obtained in 86% combined yield. Gram-scale studies were conducted to further demonstrate the synthetic potential and practical utility of the developed methodology. The biologically significant compounds 6-(tert-butyl)-2,4-diphenylquinoline (3d) and
Graphical Abstract
Figure 1: Representative examples of bioactive quinolines.
Scheme 1: C(sp2)–C(sp2) bond-cleavage strategies for quinoline synthesis.
Scheme 2: Substrate scope of various arylamines and styrenes.
Scheme 3: Scale-up studies for the synthesis of antifungal agents.
Scheme 4: Mechanistic investigations.
Scheme 5: Plausible reaction mechanism.
Synthesis of chiral cyclohexane-linked bisimidazolines
- Changmeng Xi,
- Qingshan Sun and
- Jiaxi Xu
Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140
- attempted (Scheme 2). For this purpose, tert-butyl N-[(1R,2R)-2-amino-1,2-diphenylethyl]carbamate (2h) with an acid-sensitive Boc (tert-butoxycarbonyl) protecting group was prepared in 70% yield from C2-symmetric (1R,2R)-1,2-diphenylethane-1,2-diamine (1) and Boc2O. Compound 2h was then converted to (1S,2S
Graphical Abstract
Figure 1: Bisoxazoline and bisimidazoline ligands.
Scheme 1: Synthesis of chiral cyclohexane-linked bisimidazoline ligands.
Scheme 2: Attempted synthesis of chiral cyclohexane-linked bisimidazoline 5h.
Scheme 3: Proposed reaction mechanism.
Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds
- Karu Ramesh and
- Stephen L. Bearne
Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135
- the carboxylic acid (Scheme 1B) in a manner similar to that described by Knör et al. [28]. Protection of the carboxylic acid group prior to conducting the N-Boc protection with di-tert-butyl dicarbonate ((Boc)2O) and DMAP was required to avoid competitive reaction of the carboxylic acid with (Boc)2O
- to form a tert-butyl ester, leading to unwanted side products and reduced selectivity. Once the acid was protected, the Boc group could be selectively introduced onto the indole nitrogen without side reactions. Overall, this sequence ensured clean N-Boc protection with minimal side reactions and
- are uncorrected. tert-Butyl 3-(2-methoxy-2-oxoethyl)-1H-indole-1-carboxylate (21). A solution of indol-3-yl acetic acid (20, 5.1 g, 29.0 mmol, 1.0 equiv) in dry MeOH (200 mL) was cooled to 0 °C, and SOCl2 (10.5 mL, 145 mmol, 5.0 equiv) was added slowly. After stirring for 12 h at room temperature, the
Graphical Abstract
Figure 1: Various natural indole-containing compounds isolated from Malassezia furfur.
Scheme 1: Synthetic routes to malassezione (1) from either A) an isonitrile precursor [18] or B) indole-3-acetic ...
Scheme 2: Various bis-substituted ketones prepared. a25c prepared from 25b.
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
- between β-ketoester 30 and di-tert-butyl azodicarboxylate (31), and the corresponding product 32 was obtained in 99% yield with 88% ee. A plausible reaction mechanism was proposed for this CPA-catalyzed enantioselective Groebke–Blackburn–Bienaymé reaction. As illustrated in Scheme 5b, the imine
- 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
- with both axial and central chirality, followed by 2) ring-strain and aromatization-driven elimination, which elucidating the observed unusual torsional strain-independent reactivity. In addition, products bearing a tert-butyl ester group were smoothly converted into structurally novel axially chiral
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.
Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO
- Jing Zhang,
- Guanyu Zhang,
- Hongxi Bai and
- Zhi-Xiang Yu
Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127
- alkyne moiety is installed via Sonogashira coupling reaction using aryl iodide 5. The cyclopropyl ring in 5 can be introduced via an SN2 reaction of compound 2 with tert-butyl cyclopropanecarboxylate (3). Scheme 5 summarizes the final successful execution of this route. The starting material 2 is a known
- compound [29] and can be prepared from readily available m-anisyl alcohol by using iodination and bromination reactions (see Supporting Information File 1 for the details). Subsequently, an SN2 reaction between 2 and tert-butyl cyclopropanecarboxylate (3) in the presence of LDA delivered product 4 in 87
Graphical Abstract
Scheme 1: Reported biologically active tetrahydrofluorenone-SERMs molecules.
Scheme 2: Reported synthesis routes to SERMs molecule VI.
Scheme 3: Lei’s synthesis of natural products of ent-kaurane diterpenoids (A), and natural products songorine...
Scheme 4: Retrosynthetic analysis for the synthesis of 1.
Scheme 5: Formal synthesis of SERMs molecule VI.
3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles
- Julia I. Pavlenko,
- Pavel A. Sakharov,
- Anastasiya V. Agafonova,
- Derenik A. Isadzhanyan,
- Alexander F. Khlebnikov and
- Mikhail S. Novikov
Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123
- ). Benzothienopyrrole 3b was methylated using the MeI/NaH system into 1-methyl-substituted derivative 6 in 81% yield. With the same efficiency, when compound 3b was treated with di-tert-butyl dicarbonate in the presence of 4-(dimethylamino)pyridine (DMAP), Boc-derivative 7 was obtained. Finally, the formylation of 3b
Graphical Abstract
Scheme 1: Synthesis of fused pyrroles and azoles by [3 + 2] annulation reactions of azirines.
Scheme 2: Synthesis of benzo[4,5]thieno[3,2-b]pyrroles 3.
Scheme 3: Plausible mechanism for the formation of compounds 3.
Scheme 4: Post-modifications of 1H-benzo[4,5]thieno[3,2-b]pyrrole (3b).
Scheme 5: Synthesis of pyrrolo[3,2-b]indole 10.
Scheme 6: IPrCuCl-catalyzed reactions of indoles 9b,c with azirine 2a.
Scheme 7: Ni(II)- and Cu(I)-catalyzed reactions of indole 15 with azirine 2a.
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
- demonstrated the homolytic cleavage of the N–O bond using N-(tert-butyl)-O-(1-phenylvinyl)-phenylhydroxyamide as a HAT reagent [78][79]. This compound was capable of initiating the formation of amidyl radicals through visible light activation. Although their controlled experiments showed that this method was
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
- -/trifluoroalkylation reagents, α-carbonyl alkyl bromides/alcohols, alkyl halides, and alkyl carboxylic acids, have been successfully applied to this transformation to afford 3-substituted indolin-2-ones. In 2013, Li’s group reported a novel DTBP(di-tert-butyl peroxide)-mediated oxidative 1,2-alkylarylation of
- equimolar amount of tert-butyl hydroperoxide (TBHP) as the oxidant, with the reaction conducted at 100 °C under an argon atmosphere, resulting in a 79% yield of the desired product 7a without the requirement for any metal catalyst. In terms of substrate scope, the study explored various N-arylacrylamides
- /alkylarylation of both unactivated and activated alkenes. The reaction employed β,γ-unsaturated ketoximes and N-arylacrylamides as substrates, with tert-butyl hydroperoxide (TBHP) acting as the oxidant, conducted at 100 °C in a sealed tube under an argon atmosphere for 24–48 hours. Regarding substrate scope
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.
Synthetic approach to borrelidin fragments: focus on key intermediates
- Yudhi Dwi Kurniawan,
- Zetryana Puteri Tachrim,
- Teni Ernawati,
- Faris Hermawan,
- Ima Nurasiyah and
- Muhammad Alfin Sulmantara
Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91
- , tert-butyl hydroperoxide (TBHP), and Ti(OiPr)4, resulting in the desired epoxide 63 with a 90% yield. Regioselective reductive opening of this epoxide was successfully carried out with Red-Al®, yielding diol 79. The more reactive primary alcohol in diol 79 was selectively masked as TBDPS ether 80 (94
Graphical Abstract
Figure 1: Chemical structure of borrelidin (1).
Scheme 1: Synthetic strategy for Morken’s C2–C12 intermediate 20 as reported by Uguen et al. [41].
Scheme 2: Preparation of monoacetates 37 and ent-38 by Uguen et al. [41].
Scheme 3: Preparation of sulfones 27 and ent-27 by Uguen et al. [41].
Scheme 4: Attempts to couple sulfones 27 and ent-27 with epoxides 23a–c reported by Uguen et al. [41].
Scheme 5: Modified synthetic plan for Morken’s C2–C12 intermediate by Uguen [41].
Scheme 6: Revised synthetic strategy for Morken’s C2–C12 intermediate 20 by Uguen [41].
Scheme 7: Iterative synthesis of polydeoxypropionates developed by Zhou et al. [40].
Scheme 8: Application of iterative synthesis of polydeoxypropionate to construct the C3–C11 fragment 60 of bo...
Scheme 9: Retrosynthetic analysis of borrelidin by Yadav et al. [39].
Scheme 10: Two-carbon homologation of precursor 66 in the synthesize C1–C11 fragment 61 of borrelidin [39].
Scheme 11: Synthesis of the C1–C11 fragment 61 of borrelidin from monoalcohol 65 [39].
Scheme 12: Synthetic plan for Theodorakis’ C3–C11 fragment 82 of borrelidin by Laschat et al. [38].
Scheme 13: Synthesis of Theodorakis’ C3–C11 fragment 82 from compound 88 [38].
Scheme 14: Retrosynthesis of 61 and 62b by Minnaard and Madduri [37].
Scheme 15: Synthesis of intermediate 98 by Minnaard and Madduri [37].
Scheme 16: Synthesis of Ōmura’s C1–C11 fragment 61 by Minnaard and Madduri [37].
Scheme 17: Synthesis of fragment 62b of borrelidin as proposed by Minnaard and Madduri [37].
Scheme 18: Iterative directed allylation for the synthesis of deoxypropionates by Herber and Breit [33].
Scheme 19: Iterative copper-mediated directed allyl substitution for the synthesis of Theodorakis’ C3–C11 frag...
Scheme 20: Retrosynthesis of the C3–C17 fragment of borrelidin by Iqbal and co-workers [35].
Scheme 21: Synthesis of key intermediates 137 and 147 for the synthesis of the C3–C17 fragment of borrelidin.
Scheme 22: Synthesis of the C3–C17 fragment 150a,b of borrelidin.
Scheme 23: Synthesis of the C11–C15 fragment 155a of borrelidin.
Scheme 24: Macrocyclization of borrelidin model compounds 155a and 155b using ring-closing metathesis.
Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold
- Henry S. T. Smith,
- Ben Giuliani,
- Kanchana Wijesekera,
- Kah Yean Lum,
- Sandra Duffy,
- Aaron Lock,
- Jonathan M. White,
- Vicky M. Avery and
- Rohan A. Davis
Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90
- ), 139.7 (C-9), 135.0 (C-13), 130.3 (C-6), 129.8 (2C, C-11, C-15), 129.4 (2C, C-12, C-14), 125.1 (C-10), 106.0 (C-5), 57.4 (C-18), 45.1 (2C, C-20, C-21), 37.9 (C-17); LRMS (ESI-SQ) m/z: 317 [M + H]+; HRESIMS–qTOF (m/z): [M + H]+ calcd for C15H1835ClN6, 317.1276; found, 317.1279. tert-Butyl(4-((3-(4
Graphical Abstract
Figure 1: (A) Position numbering on the pyrazine ring of 1,2,4-triazolo[4,3-a]pyrazine. (B) Illustration of i...
Scheme 1: Treatment of 1 with phenethylamine (PEA) under two different reaction conditions, (i) or (ii), gave ...
Figure 2: Key COSY (–), HMBC (→) and ROESY (↔) correlations for compound 2.
Figure 3: Thermal ellipsoid plot of compound 2.
Scheme 2: Chemical structures, reagents and conditions used to synthesise the new aminated triazolopyrazines 2...
Figure 4: Thermal ellipsoid plots for compounds 7 (A), 10 (B) and 15 (C).
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
- in situ nitro reduction using Mn powder to afford the amide intermediate 42. The acid halide once again was applied for cinnamic acid amidation. Xiao and co-workers (2021) performed a transesterification and aminolysis of the tert-butyl ester 43 simply by using PCl3 through in situ generation of the
- 89 from the corresponding dioxazolone 88 in excellent yields via reductive elimination from intermediate 90 (Scheme 26) [62]. Hu and co-workers (2019) also employed a Cu salt (Cu(OTf)2) to synthesize N-difluoroethylimide 91 from cinnamic acid (7) and tert-butyl nitrite (TBN) in good yield via
- . Similarly, Silvani and co-workers (2022) also reported a multicomponent Ugi-type reaction of cinnamic acid (7), aldehyde/ketone, (S)-β-phenyl β-aminoboronate 367, and tert-butyl isocyanide to give the corresponding pharmacophoric β-substituted β-amido boronates 368–370 in moderate yields (Scheme 80B) [136
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 total synthesis of natural products leveraging a strategy of enamide cyclization
- Chun-Yu Mi,
- Jia-Yuan Zhai and
- Xiao-Ming Zhang
Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81
- attack of the electron-rich arene on the acyliminium ion occurs from the Si-face. This stereochemical outcome is attributed to the steric discrepancy of the phenyl or tert-butyl group and the hydroxy group. The resulting tricyclic products could be further elaborated by elimination or amide reduction to
- diastereo- and enantioselectivities. The substituent on the enamide could be varied from aryl to tert-butyl groups, though the terminating aryl group still necessitates an electron-rich arene. As was found in their previous work, the steric hindrance of the phenyl or tert-butyl group was supposed to be
Graphical Abstract
Figure 1: Reactivity of enamides and enamide cyclizations.
Scheme 1: Total synthesis of (−)-dihydrolycopodine and (−)-lycopodine.
Scheme 2: Collective total synthesis of fawcettimine-type alkaloids.
Scheme 3: Total syntheses of cephalotaxine and cephalezomine H.
Scheme 4: Collective total syntheses of Cephalotaxus alkaloids.
Scheme 5: Asymmetric tandem cyclization/Pictet–Spengler reaction of tertiary enamides.
Scheme 6: Tandem cyclization/Pictet–Spengler reaction for the synthesis of chiral tetracyclic compounds.
Scheme 7: Total synthesis of (−)-cephalocyclidin A.
