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Search for "diketone" in Full Text gives 138 result(s) in Beilstein Journal of Organic Chemistry.
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
- , olefin hydrogenation, and DMP oxidation, provided diketone 125. The two carbonyl groups in 125 were then chemoselectively and stereoselectively reduced using rhodium as a catalyst to yield hydroxylated ketone 126. A further three-step transformation provided the catalytic hydrogenation precursor 127
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
- high-yielding synthesis of 23 by heating diketone 22 with PCl5 for several hours in toluene (Scheme 6B) [52]. Similarly, Jung obtained 25 in 69% yield after heating neat ketone and PCl5 (Scheme 6C) [53]. The high yield of 25 is somewhat surprising, considering the limited stability thereof. In our
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.
Recent advances in total synthesis of illisimonin A
- Juan Huang and
- Ming Yang
Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199
- into the pentacyclic diene intermediate 93 via a two-step sequence. Subsequent [4 + 2] cycloaddition of 93 with singlet oxygen yielded an unstable endoperoxide adduct 94, which rearranged to diketone 95. A five-step sequence, featuring an intramolecular aldol reaction to assemble the pentacyclic core
Graphical Abstract
Figure 1: The categorization of Illicium sesquiterpenes and representative natural products.
Figure 2: The original assigned (−)-illisimonin A, revised (−)-illisimonin A, and their different draws.
Scheme 1: Proposed biosynthetic pathway of illisimonin A by Yu et al.
Scheme 2: Rychnovsky’s racemic synthesis of illisimonin A (1).
Scheme 3: The absolute configuration revision of (−)-illisimonin A.
Scheme 4: Kalesse’s asymmetric synthesis of (−)-illisimonin A.
Scheme 5: Yang group proposed biosynthetic pathway of illisimonin A.
Scheme 6: Yang’s bioinspired synthesis of illisimonin A.
Scheme 7: Dai’s asymmetric synthesis of (–)-illisimonin A.
Scheme 8: Lu’s total synthesis of illisimonin A.
Scheme 9: Initial efforts toward the total synthesis of illisimonin A by the Lu Group.
Scheme 10: Suzuki’s synthetic effort towards illisimonin A.
Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies
- Zhi-Qi Cao,
- Jin-Bao Qiao and
- Yu-Ming Zhao
Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198
- . This work not only demonstrates the efficacy of the titanium-mediated intramolecular alkyne-1,3-diketone coupling but also provides a novel strategic approach for synthesizing natural products within this structural class. The synthesis commenced from commercially available compound 83. Sequential
Graphical Abstract
Scheme 1: Representative Ryania diterpenoids and their derivatives.
Scheme 2: Deslongchamps’s total synthesis of ryanodol (4).
Scheme 3: Deslongchamps’s total synthesis of 3-epi-ryanodol (5).
Scheme 4: Inoue’s total synthesis of ryanodol (4).
Scheme 5: Inoue’s total synthesis of ryanodine (1) from ryanodol (4).
Scheme 6: Inoue’s total synthesis of cinncassiol A (9), cinncassiol B (7), cinnzeylanol (6), and 3-epi-ryanod...
Scheme 7: Reisman’s total synthesis of (+)-ryanodol (4).
Scheme 8: Reisman’s total synthesis of (+)-ryanodine (1) and (+)-20-deoxyspiganthine (2).
Scheme 9: Micalizio’s formal total synthesis of ryanodol (4).
Scheme 10: Zhao’s total synthesis of garajonone (8).
Scheme 11: Zhao’s formal total synthesis of ryanodol (4) and ryanodine (1).
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
- allylic oxidation using H2SeO3-dioxane system to form the C30 aldehyde 47, or by the ozonolytic cleavage of the double bond between C20 and C29 to produce 20-methyl-3-ethyldiketone 48 [36]. Intramolecular nitrile–anionic cyclization of ketone 46 or diketone 48 under conditions of basic catalysis proceeded
- available (+)-sclareolide (101) as starting compound, from which key alcohol 102 was synthesized in 7 steps. Selective mesylation of the secondary alcohol in 102 followed by semipinacol rearrangement catalyzed by t-BuOK afforded diketone 104 as a pair of epimers at C12 in a 1:1 ratio, with 70% overall yield
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).
Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis
- Peng-Xi Luo,
- Jin-Xuan Yang,
- Shao-Min Fu and
- Bo Liu
Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177
- transformation of 10 via sequential Wittig reaction, dihydroxylation, and Swern oxidation generated 1,2-diketone 12, thus setting the stage for the Norrish–Yang reaction. Finally, irradiation of 12 with a compact fluorescent lamp (CFL) completed (+)-cyclobutastellettolide B (13) as the sole product in 95% yield
Graphical Abstract
Scheme 1: a) The mechanism of Norrish type II reaction and Norrish–Yang cyclization; b) The mechanism of the ...
Scheme 2: Total synthesis of (+)-cyclobutastellettolide B.
Scheme 3: Norrish–Yang cyclization and 1,2-methyl migration.
Scheme 4: Synthetic study toward phainanoids.
Scheme 5: a) Mitsunobu reaction of the C9 ketal; b) Norrish–Yang cyclization of the saturated C5–C6; c) calcu...
Scheme 6: Total synthesis of avarane-type meroterpenoids.
Scheme 7: Total synthesis of gracilisoid A.
Scheme 8: Divergent total synthesis of gracilisoids B–I.
Scheme 9: Mechanism of the late-stage biomimetic photooxidation.
Scheme 10: Asymmetric total synthesis of lycoplatyrine A.
Scheme 11: Photoreaction of pyrrolidine-derived phenyl keto amide.
Scheme 12: Photoredox reactions of naphthoquinones.
Scheme 13: Synthetic study toward γ-rubromycin.
Scheme 14: Substituent-dependent conformational preferences.
Scheme 15: Total synthesis of preussomerins EG1, EG2, and EG3.
Pathway economy in cyclization of 1,n-enynes
- Hezhen Han,
- Wenjie Mao,
- Bin Lin,
- Maosheng Cheng,
- Lu Yang and
- Yongxiang Liu
Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173
- 1,3-acyloxy migration, 6-exo-trig cyclization, and 1,5-acyl migration proceeded, affording δ-diketone-substituted cis-1,2,3,6-tetrahydropyridine derivatives 75 (Scheme 16, path a). The phosphine-ligated catalysts promoted an alternative pathway cascade involving 1,3-acyloxy migration, 6-exo-trig
Graphical Abstract
Scheme 1: Economical synthesis and pathway economy.
Scheme 2: Au(I)-catalyzed cascade cyclization paths of 1,5-enynes.
Scheme 3: Au(I)-catalyzed cyclization paths of 1,7-enynes.
Scheme 4: I2/TBHP-mediated radical cycloisomerization paths of 1,n-enyne.
Scheme 5: Au(I)-catalyzed cycloisomerization paths of 3-allyloxy-1,6-diynes.
Scheme 6: Pd(II)-catalyzed cycloisomerization paths of 2-alkynylbenzoate-cyclohexadienone.
Scheme 7: Stereoselective cyclization of 1,5-enynes.
Scheme 8: Substituent-controlled cycloisomerization of propargyl vinyl ethers.
Scheme 9: Au(I)-catalyzed pathway-controlled domino cyclization of 1,2-diphenylethynes.
Scheme 10: Au(I)-catalyzed tandem cyclo-isomerization of tryptamine-N-ethynylpropiolamide.
Scheme 11: Au(I)-catalyzed tunable cyclization of 1,6-cyclohexenylalkyne.
Scheme 12: Substituent-controlled 7-exo- and 8-endo-dig-selective cyclization of 2-propargylaminobiphenyl deri...
Scheme 13: BiCl3-catalyzed cycloisomerization of tryptamine-ynamide derivatives.
Scheme 14: Au(I)-mediated substituent-controlled cycloisomerization of 1,6-enynes.
Scheme 15: Ligand-controlled regioselective cyclization of 1,6-enynes.
Scheme 16: Ligand-dependent cycloisomerization of 1,7-enyne esters.
Scheme 17: Ligand-controlled cycloisomerization of 1,5-enynes.
Scheme 18: Ligand-controlled cyclization strategy of alkynylamide tethered alkylidenecyclopropanes.
Scheme 19: Ag(I)-mediated pathway-controlled cycloisomerization of tryptamine-ynamides.
Scheme 20: Gold-catalyzed cycloisomerization of indoles with alkynes.
Scheme 21: Catalyst-dependent cycloisomerization of dienol silyl ethers.
Scheme 22: Cycloisomerization of aromatic enynes governed by catalyst.
Scheme 23: Catalyst-dependent 1,2-migration in cyclization of 1-(indol-2-yl)-3-alkyn-1-ols.
Scheme 24: Gold-catalyzed cycloisomerization of N-propargyl-N-vinyl sulfonamides.
Scheme 25: Gold(I)-mediated enantioselective cycloisomerizations of ortho-(alkynyl)styrenes.
Scheme 26: Catalyst-controlled intramolecular cyclization of 1,7-enynes.
Scheme 27: Brønsted acid-catalyzed cycloisomerizations of tryptamine ynamides.
Scheme 28: Catalyst-controlled cyclization of indolyl homopropargyl amides.
Scheme 29: Angle strain-dominated 6-endo-trig cyclization of propargyl vinyl ethers.
Scheme 30: Angle strain-controlled cycloisomerization of alkyn-tethered indoles.
Scheme 31: Geometrical isomeration-dependent cycloisomerization of 1,3-dien-5-ynes.
Scheme 32: Temperature-controlled cyclization of 1,7-enynes.
Scheme 33: Cycloisomerizations of n-(o-ethynylaryl)acrylamides through temperature modulation.
Scheme 34: Temperature-controlled boracyclization of biphenyl-embedded 1,3,5-trien-7-ynes.
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
- reduction of diketone 28 for preparing alcohol 30 under the CBS conditions [8] with (S)-29 as the catalyst (Scheme 1) [14]. Notably, this reaction could be performed on multiple gram scales with satisfactory yield (72%) and ee value (92%). Protection of the alcohol group in 30 with TBSCl followed by
- secondary alcohol to a ketone allowed for rapid construction of bicyclic ketone 34 in high overall yield. The oxidative dehydrogenation of 34 gave α,β-unsaturated bicyclic ketone 35 smoothly. Sequential A-ring construction and functional group modifications of 35 produced the diketone 36. Subsequently, 36
- , by employing the same procedures for the synthesis of (−)-cyrneine A (7), the synthesis of (+)-allocyathin B2 (8) could also be achieved smoothly from 52 by utilizing diketone 53 as the intermediate. The diverse syntheses of these terpenoids enabled by the desymmetric enantioselective reduction of
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].
Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization
- Miao Xiao,
- Liuyang Pu,
- Qiaoli Shang,
- Lei Zhu and
- Jun Huang
Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152
- afforded the corresponding alcohol 18 in 89% yield with excellent enantioselectivity (98% ee) [25]. The hydroxy group in 18 was then protected via treatment with TBSCl in the presence of Et3N in CH2Cl2, yielding β-keto ester 15 in 52% yield. With diketone 15 in hand, we subsequently investigated the
- ester 4. Optimization of conditions to convert diketone 15 into cyclopentanone 14.a Supporting Information Supporting Information File 42: Experimental procedures, characterization data and copies of 1H and 13C NMR spectra. Acknowledgements We thank Prof. Zhen Yang (Peking University) for helpful
Graphical Abstract
Scheme 1: Representative prostaglandins and general synthetic strategy toward PGDM methyl ester 4.
Scheme 2: Retrosynthetic analysis for the first generation synthesis of PGDM methyl ester 4.
Scheme 3: Synthesis of bicyclic ketal 25.
Scheme 4: Retrosynthetic analysis for the second-generation synthesis of tricyclic PGDM methyl ester 4.
Scheme 5: Asymmetric total synthesis of tricyclic-PGDM methyl ester 4.
Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis
- Lihua Wei,
- Rui Yang,
- Zhifeng Shi and
- Zhiqiang Ma
Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151
- between 80 and 81 gave diester 82. Through a ten-step sequence including an aza-Michael reaction, diester 82 was converted into diketone 83, which was further transformed into (−)-petrosin (84) via RCM reaction and hydrogenation. For the synthesis of (+)-petrosin (86) (Scheme 13b), a similar strategy was
Graphical Abstract
Scheme 1: General mechanism of a lipase-catalyzed esterification.
Scheme 2: Shishido’s synthesis of (−)-xanthorrhizol (4) and (+)-heliannuol D (8).
Scheme 3: Shishido’s synthesis of a) (−)-heliannuol A (15) and b) heliannuol G (20) and heliannuol H (21).
Scheme 4: Deska’s synthesis of hyperione A (30) and ent-hyperione B (31).
Scheme 5: Huang’s synthesis of (+)-brazilin (37).
Scheme 6: Shishido’s synthesis of (−)-heliannuol D (42) and (+)-heliannuol A (43).
Scheme 7: Chênevert’s synthesis of (S)-α-tocotrienol (49).
Scheme 8: Kita’s synthesis of monoester 53.
Scheme 9: Kita’s synthesis of fredericamycin A (60).
Scheme 10: Takabe’s synthesis of (E)-3,7-dimethyl-2-octene-1,8-diol (64).
Scheme 11: Takabe’s synthesis of (18S)-variabilin (70).
Scheme 12: Kawasaki’s synthesis of (S)-Rosaphen (74) and (R)-Rosaphen (75).
Scheme 13: Tokuyama’s synthesis of a) (−)-petrosin (84) and b) (+)-petrosin (86).
Scheme 14: Fukuyama’s synthesis of leustroducsin B (96).
Scheme 15: Nanda’s synthesis of a) fragment 100, b) fragment 106 and c) (−)-rasfonin (109).
Scheme 16: Davies’ synthesis of (+)-pilocarpine (115) and (+)-isopilocarpine (116).
Scheme 17: Ōmura’s synthesis of salinosporamide A (125).
Scheme 18: Kang’s synthesis of ʟ-cladinose (124) and its derivative.
Scheme 19: Kang’s preparation of fragment 139.
Scheme 20: Kang’s synthesis of azithromycin (149).
Scheme 21: Kang’s synthesis of (−)-dysiherbaine (156).
Scheme 22: Kang’s synthesis of (−)-kaitocephalin (166).
Scheme 23: Kang’s synthesis of laidlomycin (180).
Scheme 24: Snyder’s synthesis of arboridinine (190).
Scheme 25: Ma’s synthesis of (+)-alstrostine G (203).
Scheme 26: Trost’s synthesis of (−)-18-epi-peloruside A (215).
Scheme 27: Lindel’s synthesis of (–)-dihydroraputindole (223).
Scheme 28: Iwata’s synthesis of a) (−)-talaromycin B (232) and b) (+)-talaromycin A (235).
Scheme 29: Cook’s synthesis of a) (−)-vincamajinine (240) and b) (−)-11-methoxy-17-epivincamajine (245).
Scheme 30: Cook’s synthesis of (+)-dehydrovoachalotine (249) and voachalotine (250).
Scheme 31: Cook’s synthesis of a) (−)-12-methoxy-Nb-methylvoachalotine (257) and b) (+)-polyneuridine, macusin...
Scheme 32: Trauner’s synthesis of stephadiamine (273).
Scheme 33: Garg’s synthesis of (–)-ψ-akuammigine (285).
Scheme 34: Ding’s synthesis of (+)-18-benzoyldavisinol (293) and (+)-davisinol (294).
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 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
- cyclopentane ring, dihydroxylation, and oxidation of the diol to a diketone, produced intermediate 25 in its enol form. From this common intermediate, regioselective etherification at the less hindered position formed an enol ether. Final reduction of both the amide and the ketone using alane completed the
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.
Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions
- Dmitry E. Shybanov,
- Maxim E. Kukushkin,
- Eugene V. Babaev,
- Nikolai V. Zyk and
- Elena K. Beloglazkina
Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18
- Interaction of 1,3-diketone 1 with formaldehyde First, we investigated the ability of formaldehyde to interact with 1,3-diketone 1 using the diffusion mixing technique. For this purpose, we carried out a series of reactions in a very simple device consisting of a large vial with formalin, inside which we
- %, respectively, when carrying out the reaction in chloroform or methanol over two days (Table 1, entries 3 and 7). In turn, in a system of two vials with diameters of 3.7 and 7.5 cm, and with a loading of diketone 1 that was five times greater, more than two thirds of the starting compound reacted within 24 h
- (Table 1, entries 11 and 13). Apparently, an increase in the surface area of the reaction solution promoted more efficient absorption of CH2O molecules, which accelerated the condensation reaction. The reaction of formaldehyde and diketone 1 in chloroform and acetonitrile predominantly led to diketo
Graphical Abstract
Scheme 1: Knoevenagel and Diels–Alder reactions in the multicomponent synthesis of substituted cyclohexadiene...
Figure 1: Equipment for carrying out reactions by the diffusion mixing method.
Scheme 2: Interaction of diketone 1 with formaldehyde under the diffusion mixing conditions.
Scheme 3: Products of three-component reactions of methylene derivatives, formaldehyde and various dienes.
Scheme 4: Proposed mechanism for the formation of compounds 8 and 9 in the presence of ʟ-proline.
Scheme 5: Interconversion of derivatives 8 and 9.
Scheme 6: Interaction of 4a/4b and 5a/5b mixtures with bromine.
Recent advances in electrochemical copper catalysis for modern organic synthesis
- Yemin Kim and
- Won Jun Jang
Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9
- anodic oxidation of chloride ions, thus replacing stoichiometric chemical oxidants. This catalytic electrochemical chlorination method is suitable for β-ketoesters 68 with electron-withdrawing or electron-donating groups on aryl substituents, as well as for β-diketone, and β-ketoamides. In 2020, Fang
Graphical Abstract
Figure 1: General mechanisms of traditional and radical-mediated cross-coupling reactions.
Figure 2: Types of electrocatalysis (using anodic oxidation).
Figure 3: Recent developments and features of electrochemical copper catalysis.
Figure 4: Scheme and proposed mechanism for Cu-catalyzed alkynylation and annulation of benzamide.
Figure 5: Scheme and proposed mechanism for Cu-catalyzed asymmetric C–H alkynylation.
Figure 6: Scheme for Cu/TEMPO-catalyzed C–H alkenylation of THIQs.
Figure 7: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical enantioselective cyanation of b...
Figure 8: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical asymmetric heteroarylcyanation ...
Figure 9: Scheme and proposed mechanism for Cu-catalyzed enantioselective regiodivergent cross-dehydrogenativ...
Figure 10: Scheme and proposed mechanism for Cu/Ni-catalyzed stereodivergent homocoupling of benzoxazolyl acet...
Figure 11: Scheme and proposed mechanism for Cu-catalyzed electrochemical amination.
Figure 12: Scheme and proposed mechanism for Cu-catalyzed electrochemical azidation of N-arylenamines and annu...
Figure 13: Scheme and proposed mechanism for Cu-catalyzed electrochemical halogenation.
Figure 14: Scheme and proposed mechanism for Cu-catalyzed asymmetric cyanophosphinoylation of vinylarenes.
Figure 15: Scheme and proposed mechanism for Cu/Co dual-catalyzed asymmetric hydrocyanation of alkenes.
Figure 16: Scheme and proposed mechanism for Cu-catalyzed electrochemical diazidation of olefins.
Figure 17: Scheme and proposed mechanism for Cu-catalyzed electrochemical azidocyanation of alkenes.
Figure 18: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical asymmetric decarboxylative cyan...
Figure 19: Scheme and proposed mechanism for electrocatalytic Chan–Lam coupling.
Surprising acidity for the methylene of 1,3-indenocorannulenes?
- Shi Liu,
- Märt Lõkov,
- Sofja Tshepelevitsh,
- Ivo Leito,
- Kim K. Baldridge and
- Jay S. Siegel
Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260
- compounds tend to deprotonate to form highly stable anions. The air stability of TBF conforms to that model. In contrast, although the dianion of BFC can be generated with tert-butoxide under inert atmosphere, in the presence of water it quenches and exposed to oxygen it oxidizes to form the diketone
Graphical Abstract
Scheme 1: Aromatic stabilization energy across a series of small aromatics (upper); graphical depiction of th...
Scheme 2: Clar–Loschmidt graphs: [upper] defining the relationship of the molecular fragment to the graph nod...
Scheme 3: CL graph perspective on acidic PAH-CpHs; pentabenzocorannulene and pentabenzoazocorannulene (upper)...
Mechanochemical difluoromethylations of ketones
- Jinbo Ke,
- Pit van Bonn and
- Carsten Bolm
Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235
- ketones reacted well too. Accordingly, 3j was obtained in 42% yield. Enone 1k gave 3k in 51% yield, and after isolation by column chromatography the product was obtained in 13% yield. Difluoromethyl enol ether 3l was formed from diketone 1l in 25% yield. Finally, conversions of the two cyclic ketones 1m
Graphical Abstract
Scheme 1: Overview over difluoromethyl enol ether syntheses from acyclic and cyclic 1,3-diones (A), acyclic k...
Scheme 2: Attempted difluoromethylation of 1a in solution. The reactions were performed on a 0.2 mmol scale. ...
Scheme 3: Scope of ketones. The yields were determined by 1H NMR spectroscopy using 1,2-dichloroethane as the...
Scheme 4: Proposed mechanism (A) and mechanistic investigations (B and C). The yields were determined by 1H N...
Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation
- Andrey R. Galeev,
- Maksim V. Dmitriev,
- Alexander S. Novikov and
- Andrey N. Maslivets
Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188
- -diketones has been developed. The electron-withdrawing power of the heterocyclic substituent (which can be estimated on the basis of calculated Hammett constants) in the 1,3-diketone plays a pivotal role in the studied reaction. The series of meta-hetarylanilines prepared (21–85% isolated yield
- ) demonstrates the synthetic utility of the developed method. Keywords: aniline; benzannulation; condensation; 1,3-diketone; Hammett constants; terphenyl; Introduction The aniline moiety is omnipresent in the synthetic chemistry with applications ranging from building blocks to catalysis [1][2][3][4]. Among
- interrupted Kröhnke reaction (Scheme 1B) [51][52]. The main step of this process is an intermolecular cyclization of the formed 1,5-diketone followed by aromatization. Previously we have shown that 1,3-diketones bearing an electron-withdrawing group (EWG) adjacent to one of the carbonyls readily react with in
Graphical Abstract
Figure 1: The meta-hetarylaniline motif in bioactive molecules.
Scheme 1: Strategies to access meta-substituted anilines.
Figure 2: The model series of synthesized 1,3-diketones and corresponding calculated Hammett constants of het...
Scheme 2: Synthesis of meta-substituted anilines from 1,2,4-oxadiazol-5-yl substituted 1,3-diketone 1a. Condi...
Scheme 3: Synthesis of meta-substituted anilines from 1,3,4-oxadiazol-substituted 1,3-diketone 1b. Conditions...
Scheme 4: Synthesis of meta-substituted anilines from benzothiazol-2-yl and oxazol-2-yl-substituted 1,3-diket...
Scheme 5: Synthesis of meta-substituted aniline from isoxazol-3-yl-substituted 1,3-diketone 1e. Conditions B: ...
Figure 3: Scope of functionalized amines in three-component condensation. Conditions A: 1a,b,h,i (0.2–0.5 mmo...
Scheme 6: Proposed mechanism for the formation of meta-substituted anilines 3 via three-component benzannulat...
Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps
- Ignaz Betcke,
- Alissa C. Götzinger,
- Maryna M. Kornet and
- Thomas J. J. Müller
Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178
- approach was also used to synthesize pyrazoles since the intermediary-formed diketone 18 forms the corresponding pyrazoles 17 in a Knorr reaction with 2-hydrazinyl-4-phenylthiazoles 15 in a one-pot process (Scheme 4) [52]. Piperidine was used as a catalyst for the Knoevenagel condensation. Remarkably
Graphical Abstract
Scheme 1: Consecutive three-component synthesis of pyrazoles 1 via in situ-formed 1,3-diketones 2 [44].
Scheme 2: Consecutive three-component synthesis of 4-ethoxycarbonylpyrazoles 5 via SmCl3-catalyzed acylation ...
Scheme 3: Consecutive four-component synthesis of 1-(thiazol-2-yl)pyrazole-3-carboxylates 8 [51].
Scheme 4: Three-component synthesis of thiazolylpyrazoles 17 via in situ formation of acetoacetylcoumarins 18 ...
Scheme 5: Consecutive pseudo-four-component and four-component synthesis of pyrazoles 21 from sodium acetylac...
Scheme 6: Consecutive three-component synthesis of 1-substituted pyrazoles 24 from boronic acids, di(Boc)diim...
Scheme 7: Consecutive three-component synthesis of N-arylpyrazoles 25 via in situ formation of aryl-di(Boc)hy...
Scheme 8: Consecutive three-component synthesis of 1,3,4-substituted pyrazoles 27 and 28 from methylhydrazine...
Scheme 9: Consecutive three-component synthesis of 4-allylpyrazoles 32 via oxidative allylation of 1,3-dicarb...
Scheme 10: Pseudo-five-component synthesis of tris(pyrazolyl)methanes 35 [61].
Scheme 11: Pseudo-three-component synthesis of 5-(indol-3-yl)pyrazoles 39 from 1,3,5-triketones 38 [64].
Scheme 12: Three-component synthesis of thiazolylpyrazoles 43 [65].
Scheme 13: Three-component synthesis of triazolo[3,4-b]-1,3,4-thiadiazin-3-yl substituted 5-aminopyrazoles 47 [67]....
Scheme 14: Consecutive three-component synthesis of 5-aminopyrazoles 49 via formation of β-oxothioamides 50 [68].
Scheme 15: Synthesis of 3,4-biarylpyrazoles 52 from aryl halides, α-bromocinnamaldehyde, and tosylhydrazine vi...
Scheme 16: Consecutive three-component synthesis of 3,4-substituted pyrazoles 57 from iodochromones 55 by Suzu...
Scheme 17: Pseudo-four-component synthesis of pyrazolyl-2-pyrazolines 59 by ring opening/ring closing cyclocon...
Scheme 18: Consecutive three-component synthesis of pyrazoles 61 [77].
Scheme 19: Three-component synthesis of pyrazoles 62 from malononitrile, aldehydes, and hydrazines [78-90].
Scheme 20: Four-component synthesis of pyrano[2,3-c]pyrazoles 63 [91].
Scheme 21: Three-component synthesis of persubstituted pyrazoles 65 from aldehydes, β-ketoesters, and hydrazin...
Scheme 22: Three-component synthesis of pyrazol-4-carbodithioates 67 [100].
Scheme 23: Regioselective three-component synthesis of persubstituted pyrazoles 68 catalyzed by ionic liquid [...
Scheme 24: Consecutive three-component synthesis of 4-halopyrazoles 69 and anellated pyrazoles 70 [102].
Scheme 25: Three-component synthesis of 2,2,2-trifluoroethyl pyrazole-5-carboxylates 72 [103].
Scheme 26: Synthesis of pyrazoles 75 in a one-pot process via carbonylative Heck coupling and subsequent cycli...
Scheme 27: Copper-catalyzed three-component synthesis of 1,3-substituted pyrazoles 76 [105].
Scheme 28: Pseudo-three-component synthesis of bis(pyrazolyl)methanes 78 by ring opening-ring closing cyclocon...
Scheme 29: Three-component synthesis of 1,4,5-substituted pyrazoles 80 [107].
Scheme 30: Consecutive three-component synthesis of 3,5-bis(fluoroalkyl)pyrazoles 83 [111].
Scheme 31: Consecutive three-component synthesis of difluoromethanesulfonyl-functionalized pyrazole 88 [114].
Scheme 32: Consecutive three-component synthesis of perfluoroalkyl-substituted fluoropyrazoles 91 [115].
Scheme 33: Regioselective consecutive three-component synthesis of 1,3,5-substituted pyrazoles 93 [116].
Scheme 34: Three-component synthesis of pyrazoles 96 mediated by trimethyl phosphite [117].
Scheme 35: One-pot synthesis of pyrazoles 99 via Liebeskind–Srogl cross-coupling/cyclocondensation [118].
Scheme 36: Synthesis of 1,3,5-substituted pyrazoles 101 via domino condensation/Suzuki–Miyaura cross-coupling ...
Scheme 37: Consecutive three-component synthesis of 1,3,5-trisubstituted pyrazoles 102 and 103 by Sonogashira ...
Scheme 38: Polymer analogous consecutive three-component synthesis of pyrazole-based polymers 107 [132].
Scheme 39: Synthesis of 1,3,5-substituted pyrazoles 108 by sequentially Pd-catalyzed Kumada–Sonogashira cycloc...
Scheme 40: Consecutive four-step one-pot synthesis of 1,3,4,5-substituted pyrazoles 110 [137].
Scheme 41: Four-component synthesis of pyrazoles 113, 115, and 117 via Sonogashira coupling and subsequent Suz...
Scheme 42: Consecutive four- or five-component synthesis for the preparation of 4-pyrazoly-1,2,3-triazoles 119...
Scheme 43: Four-component synthesis of pyrazoles 121 via alkynone formation by carbonylative Pd-catalyzed coup...
Scheme 44: Preparation of 3-azulenyl pyrazoles 124 by glyoxylation, decarbonylative Sonogashira coupling, and ...
Scheme 45: Four-component synthesis of a 3-indoloylpyrazole 128 [147].
Scheme 46: Two-step synthesis of 5-acylpyrazoles 132 via glyoxylation-Stephen–Castro sequence and subsequent c...
Scheme 47: Copper on iron mediated consecutive three-component synthesis of 3,5-substituted pyrazoles 136 [150].
Scheme 48: Consecutive three-component synthesis of 3-substituted pyrazoles 141 by Sonogashira coupling and su...
Scheme 49: Consecutive three-component synthesis of pyrazoles 143 initiated by Cu(I)-catalyzed carboxylation o...
Scheme 50: Consecutive three-component synthesis of benzamide-substituted pyrazoles 146 starting from N-phthal...
Scheme 51: Consecutive three-component synthesis of 1,3,5-substituted pyrazoles 148 [156].
Scheme 52: Three-component synthesis of 4-ninhydrin-substituted pyrazoles 151 [158].
Scheme 53: Consecutive four-component synthesis of 4-(oxoindol)-1-phenylpyrazole-3-carboxylates 155 [159].
Scheme 54: Three-component synthesis of pyrazoles 160 [160].
Scheme 55: Consecutive three-component synthesis of pyrazoles 165 [162].
Scheme 56: Consecutive three-component synthesis of 3,5-disubstituted and 3-substituted pyrazoles 168 and 169 ...
Scheme 57: Three-component synthesis of 3,4,5-substituted pyrazoles 171 via 1,3-dipolar cycloaddition of vinyl...
Scheme 58: Three-component synthesis of pyrazoles 173 and 174 from aldehydes, tosylhydrazine, and vinylidene c...
Scheme 59: Three-component synthesis of pyrazoles 175 from glyoxyl hydrates, tosylhydrazine, and electron-defi...
Scheme 60: Pseudo-four-component synthesis of pyrazoles 177 from glyoxyl hydrates, tosylhydrazine, and aldehyd...
Scheme 61: Consecutive three-component synthesis of pyrazoles 179 via Knoevenagel-cycloaddition sequence [179].
Scheme 62: Three-component synthesis of 5-dimethylphosphonate substituted pyrazoles 182 from aldehydes, the Be...
Scheme 63: Consecutive three-component synthesis of 5-(dimethyl phosphonate)-substituted pyrazoles 185 from al...
Scheme 64: Three-component synthesis of 5-(dimethyl phosphonate)-substituted pyrazoles 187 from aldehydes, the...
Scheme 65: Three-component synthesis of 5-diethylphosphonate/5-phenylsulfonyl substituted pyrazoles 189 from a...
Scheme 66: Pseudo-three-component synthesis of 3-(dimethyl phosphonate)-substituted pyrazoles 190 [185].
Scheme 67: Three-component synthesis of 3-trifluoromethylpyrazoles 193 [186].
Scheme 68: Consecutive three-component synthesis of 5-stannyl-substituted 4-fluoropyrazole 197 [191,192].
Scheme 69: Pseudo-three-component synthesis of 3,5-diacyl-4-arylpyrazoles 199 [195].
Scheme 70: Three-component synthesis of pyrazoles 204 via nitrilimines [196].
Scheme 71: Three-component synthesis of 1,3,5-substituted pyrazoles 206 via formation of nitrilimines and sali...
Scheme 72: Pseudo four-component synthesis of pyrazoles 209 from acetylene dicarboxylates 147, hydrazonyl chlo...
Scheme 73: Consecutive three-component synthesis of pyrazoles 213 via syndnones 214 [200].
Scheme 74: Consecutive three-component synthesis of pyrazoles 216 via in situ-formed diazomethinimines 217 [201].
Scheme 75: Consecutive three-component synthesis of 3-methylthiopyrazoles 219 from aldehydes, hydrazine, and 1...
Scheme 76: Three-component synthesis of 1,3,5-substituted pyrazoles 220 from aldehydes, hydrazines, and termin...
Scheme 77: Three-component synthesis of 1,3,4,5-substituted pyrazoles 222 from aldehydes, hydrazines, and DMAD ...
Scheme 78: Pseudo three-component synthesis of pyrazoles 224 from sulfonyl hydrazone and benzyl acrylate under...
Scheme 79: Titanium-catalyzed consecutive four-component synthesis of pyrazoles 225 via enamino imines 226 [211]. a...
Scheme 80: Titanium-catalyzed three-component synthesis of pyrazoles 227 via enhydrazino imine complex interme...
Scheme 81: Pseudo-three-component synthesis of pyrazoles 229 via Glaser coupling of terminal alkynes and photo...
Scheme 82: Copper(II)acetate-mediated three-component synthesis of pyrazoles 232 [216].
Scheme 83: Copper-catalyzed three-component synthesis of 1,3,4-substituted pyrazole 234 from oxime acetates, a...
Scheme 84: Three-component synthesis of 3-trifluoroethylpyrazoles 239 [218].
Scheme 85: Pseudo-three-component synthesis of 1,4-bisulfonyl-substituted pyrazoles 242 [219].
Scheme 86: Three-component synthesis of 4-hydroxypyrazole 246 [221].
Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)
- Hiwot M. Tiruye,
- Solon Economopoulos and
- Kåre B. Jørgensen
Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153
- aromatic hydrocarbons; Introduction Quinones and their derivatives are applied in various fields such as chemical, environmental, and pharmaceutical industries [1][2][3][4]. Their cyclic diketone structures can easily transform into intramolecular unsaturated structures, and their distinct physical
Graphical Abstract
Scheme 1: Formation of phenoxonium cation in the anodic oxidation of phenol performed under neutral or weakly...
Scheme 2: Anodic oxidation reported by Swenton et al. [37].
Figure 1: Cyclic voltammograms of PAPs first scan at 0.1 V/s in 0.1 M [NBu4] [PF6] in MeCN and UV–vis spectra...
Scheme 3: Proposed mechanism for the formation of p-dimethoxy acetals in the anodic oxidation of 1b and 3b.
Figure 2: Resonance structures of the phenoxonium cation formed from 2-chrysenol (3a).
Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps
- Qian Liu and
- Glen P. Miller
Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97
- congestion to the highly reactive 1,3-carbons on the furan ring. Thus, phthaloyl chloride was reacted with mesitylene or 1,3,5-triethylbenzene to produce the corresponding diketones 21 and 22. Each diketone was in turn reacted with zinc metal in glacial acetic acid [9] to afford the corresponding 1,3
- substituents, respectively, were also attempted but without success. In these cases, the sterically congesting ortho isopropyl and tert-butyl groups stymie the Friedel–Crafts acylation step leading to diketone (Scheme 1). Experimental and computational studies of 1,3-diarylisoacenofurans Purified
Graphical Abstract
Figure 1: Neutral, closed-shell resonance forms for pentacene highlighting Clar aromatic sextets (see [1]) and t...
Figure 2: The only neutral, closed-shell resonance form for 5-ring isotetracenofuran with its highly delocali...
Figure 3: DFT calculated HOMO–LUMO gaps of acenes and isoacenofurans performed at the B3LYP/6-311+G(d,p)//B3L...
Figure 4: A structural rendering of 1,3-dimesitylisobenzofuran showing the requirement for non-planar mesityl...
Scheme 1: Synthesis of 1,3-diarylisobenzofurans 3 and 23.
Figure 5: UV–vis (top) and fluorescence (middle) spectra for 10−6 M solutions of 1,3-diarylisobenzofurans 2, 3...
Figure 6: Calculated HOMO and LUMO orbitals for parent isobenzofuran (1) and 1,3-diarylisobenzofuran derivati...
Figure 7: UV–vis spectra calculated for 1,3-diarylisobenzofuran derivatives 1, 2, 3, 23, 24 and 25 using a DF...
Figure 8: UV–vis spectra for the reactions of 2 (top) and 3 (bottom) with a 7000-fold excess of DMAD in CH2Cl2...
Scheme 2: Reactions between 1,3-diarylisobenzofurans 2, 3 and 23 and DMAD to produce Diels–Alder adducts 26, ...
Scheme 3: Synthesis of 1,3-dimesitylisobenzofuran (3).
Scheme 4: Synthesis of 1,2-phenylenebis(mesitylmethanone) (21).
Scheme 5: Synthesis of 1,2-phenylenebis((2,4,6-triethylphenyl)methanone) (22).
Scheme 6: Synthesis of 1,3-bis(2,4,6-triethylphenyl)isobenzofuran (23).
Scheme 7: Synthesis of dimethyl 1,4-diphenyl-1,4-dihydro-1,4-epoxynaphthalene-2,3-dicarboxylate (26).
Scheme 8: Synthesis of dimethyl 1,4-dimesityl-1,4-dihydro-1,4-epoxynaphthalene-2,3-dicarboxylate (27).
Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives
- Tural N. Akhmedov,
- Ajeet Kumar,
- Daken J. Starkenburg,
- Kyle J. Chesney,
- Khalil A. Abboud,
- Novruz G. Akhmedov,
- Jiangeng Xue and
- Ronald K. Castellano
Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92
- high reactivity of intermediate 7a (Scheme 4). After optimizing the successful synthesis of alkoxylated and diketone derivatives of 7a, we were intrigued to investigate whether other dicyanopyrazinoquinoxaline derivatives could undergo a similar transformation. To assess the efficacy of the reaction
Graphical Abstract
Figure 1: Chemical structures of H-bonding N-heteroacenes synthesized by Miao et al. and Bunz et al. (a) [22,23]. Pr...
Scheme 1: Synthesis of dicyanopyrazinoquinoxaline derivatives 1a–7a.
Scheme 2: Synthesis of bis-alkoxy-substituted π-conjugated phenanthrolines 16a, 16b, 16c, and 16d.
Scheme 3: An alternative synthetic route to access 7a.
Scheme 4: Synthesis of DPQDs 1b–7b from their corresponding DCPQs 1a–7a. *THF/H2O/1,4-dioxane (4:5:1). **in s...
Figure 2: TGA of 1a–6a (a) and 1b–7b (b) obtained at 10 °C/min under nitrogen.
Figure 3: Absorption spectra (20 μM) for a) DCPQs 1a–6a and b) DPQDs 1b–7b in dimethyl sulfoxide.
Figure 4: Calculated HOMO (below) and LUMO (above) energies by DFT analysis (B3LYP/6-31+G* level of theory), ...
Figure 5: Calculated HOMO (below) and LUMO (above) energies by DFT analysis (B3LYP/6-31+G* level of theory), ...
Figure 6: Asymmetric unit of DPQD 2b with important bond lengths highlighted (a). Torsion angles of 4.33° and...
(Bio)isosteres of ortho- and meta-substituted benzenes
- H. Erik Diepers and
- Johannes C. L. Walker
Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78
- ), deprotection, decarboxylation, oxidation, nitrogen extrusion (to cyclobutadiene) and Diels–Alder reaction yielded annulated tricycle 164. Further intramolecular [2 + 2] cycloaddition formed cubane precursor 165. From diketone 165, 1,3-cubane 166 was obtained by Favorskii ring contraction followed by
Graphical Abstract
Figure 1: Scaffolds commonly reported as bioisosteric replacements of para-substituted benzene and examples p...
Figure 2: 1,2-BCPs as isosteres for ortho-and meta-substituted benzenes: comparison of reported exit vector p...
Scheme 1: 1,2-Disubstituted bicyclo[1.1.1]pentanes as isosteres of ortho-substituted benzenes. A: Baran, Coll...
Scheme 2: Synthesis of 1,2-BCPs from BCP 15 by bridge C–H bromination as reported by MacMillan and co-workers ...
Figure 3: Comparative physicochemical data of telmisartan, lomitapide and their BCP isosteres [26,33]. Shake flask d...
Figure 4: 1,2-Disubstituted bicyclo[2.1.1]hexanes as isosteres of ortho-benzenes: Exit vector parameters of t...
Scheme 3: Synthesis of 1,2-disubstituted bicyclo[2.1.1]hexanes via alkene insertion into bicyclo[1.1.0]butane...
Scheme 4: Synthesis of 1,2-disubstituted bicyclo[2.1.1]hexanes via intramolecular crossed [2 + 2] cycloadditi...
Figure 5: Comparison of physicochemical data of fluxapyroxad and boscalid and their 1,2-BCH bioisosteres [36]. Sh...
Figure 6: Antifungal activity of fluxapyroxad, its 1,5-BCH bioisostere (±)-55, boscalid and its bioisostere 1...
Figure 7: 1,5-Disubstituted bicyclo[2.1.1]hexanes as isosteres of ortho-substituted benzenes. Comparison of e...
Scheme 5: Synthesis of 1,5-disubstituted bicyclo[2.1.1]hexanes as isosteres of ortho-benzenes via intramolecu...
Figure 8: Comparison of physicochemical data of fluxapyroxad and boscalid and their 1,5-BCH bioisosteres [45]. Sh...
Figure 9: Antifungal activity of fluxapyroxad, its 1,5-BCH bioisostere (±)-64, boscalid and its bioisostere 1...
Figure 10: 1,5-Disubstituted 3-oxabicylco[2.1.1]hexanes as isosteres for ortho-benzenes: Comparison of exit ve...
Scheme 6: Synthesis of 1,5-disubstituted 3-oxabicyclo[2.1.1]hexanes as isosteres for ortho-benzenes via intra...
Figure 11: Comparison of physicochemical data of fluxapyroxad and boscalid and their 3-oxa-1,5-BCH bioisostere...
Figure 12: Antifungal activity of fluxapyroxad and boscalid and their 3-oxa-1,5-BCH bioisosteres (±)-75 and (±...
Figure 13: 1,2-Disubstituted bicyclo[3.1.1]heptanes as isosteres of ortho-benzenes. Schematic representation o...
Scheme 7: Synthesis of 1,2-disubstituted bicyclo[3.1.1]heptanes as isosteres for ortho-benzenes via alkene in...
Figure 14: 1,2-Disubstituted stellanes as ortho-benzene isosteres: Comparison of selected exit vector paramete...
Scheme 8: Synthesis of 1,2-disubstituted stellanes as isosteres for ortho-benzenes reported by Ryabukhin, Vol...
Figure 15: 1,2-Disubstituted cubanes as ortho-benzene isosteres: Comparison of substituent distances and angle...
Scheme 9: Synthesis of 1,2-disubsituted cubanes as isosteres for ortho-benzenes. A: Synthesis of 1,2-cubane d...
Figure 16: 1,3-Disubstituted bicyclo[2.1.1]hexanes as isosteres of meta-benzenes: comparative exit vector para...
Scheme 10: Synthesis of 1,3-disubstituted bicyclo[2.1.1]hexanes as isosteres for meta-benzenes reported by Wal...
Figure 17: 1,4-Disubstituted bicyclo[2.1.1]hexanes as isosteres of meta-benzenes: comparative exit vector para...
Scheme 11: Synthesis of 1,4-disubstituted bicyclo[2.1.1}hexanes as isosteres for ortho-benzenes via intramolec...
Figure 18: 1,4-Disubstituted-2-oxabicyclo[2.1.1]hexanes as meta-benzene isosteres: comparison of selected exit...
Scheme 12: Synthesis of 1,4-disubstituted 2-oxabicyclo[2.1.1]hexanes as isosteres for meta-benzenes. A: Mykhai...
Figure 19: Comparative physicochemical data for 2- and 3-oxa-1,4-BCHs and para-substituted benzene equivalents...
Figure 20: 1,5-Disubstituted bicyclo[3.1.1]heptanes as isosteres of meta-benzenes: comparison of exit vector p...
Scheme 13: Synthesis of [3.1.1]propellane as a precursor for 1,5-disubsituted bicyclo[3.1.1]heptanes. A: aGass...
Scheme 14: Synthesis of iodine-substituted 1,5-disubstituted bicyclo[3.1.1]heptanes as isosteres for meta-benz...
Scheme 15: Synthesis of nitrogen-, chalcogen- and tin-substituted 1,5-disubstituted bicyclo[3.1.1]heptanes as ...
Figure 21: Comparative physicochemical data of URB597 and 1,5-BCHep isostere 146 [27]. Kinetic aqueous solubility ...
Figure 22: [2]-Ladderanes as isosteres of meta-benzenes: comparison of reported exit vector parameters [63].
Scheme 16: Synthesis of cis-2,6-disubstituted bicyclo[2.2.0]hexanes as isosteres for meta-benzenes. A: Brown a...
Figure 23: Comparative physicochemical data of meta-benzene 158 and [2]-ladderane isostere 159 [63]. Partition coe...
Figure 24: 1,3-Disubstituted cubanes as isosteres of meta-benzenes: comparison of selected exit vector paramet...
Scheme 17: Synthesis of 1,3-disubsituted cubanes as isosteres for meta-benzenes. A: MacMillan and co-workers’ ...
Figure 25: Comparative physicochemical data of lumacaftor and its 1,3-cubane bioisostere 183 [51]. Distribution co...
Figure 26: 1,3-Disubstituted cuneanes as isosteres of meta-benzenes: comparison of selected exit vector parame...
Scheme 18: Synthesis of 1,3-cuneanes as isosteres of meta-benzene. A: Synthesis of 1,3-cuneanes reported by La...
Figure 27: Comparative physicochemical data of sonidegib and its 1,3-cuneane isostere 190 [71]. aSolubility was to...
Figure 28: Exemplary polysubstituted scaffolds related to disubstituted scaffolds suggested as isosteres of or...
Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas
- Alexander S. Hampton,
- David R. W. Hodgson,
- Graham McDougald,
- Linhua Wang and
- Graham Sandford
Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41
- agents offers an alternative fluorination route, for example, the reactions of MeCN solutions of 1,3-diketones with electrophilic fluorinating agents such as Selectfluor eventually give the corresponding 2,2-difluoro-1,3-diketone derivatives [12]. Monofluorination of the 1,3-diketone substrates is rapid
- , but the second fluorination step occurs only after reaction for several days. In the solid phase, mechanical milling of the diketone substrate with solid Selectfluor in the presence of sodium carbonate [13][14], and reaction of ketones with a strong base and an N–F reagent give rise to the
- corresponding 2,2-difluoroketones [15]. In related kinetic studies concerning the electrophilic 2-fluorination of 1,3-diketones with Selectfluor [16][17], we demonstrated that the rate-determining step for difluorination was enolization of the intermediate 2-fluoro-1,3-diketone. Monofluorination of 1,3
Graphical Abstract
Scheme 1: Monofluorination of 1,3-diphenylpropane-1,3-dione with Selectfluor.
Scheme 2: Synthesis of 2,2-difluoro-1,3-diphenylpropane-1,3-dione (3a).
Figure 1: Molecular structure of 2,2-difluoro-1,3-diphenylpropane-1,3-dione (3a).
Figure 2: Crystal packing structure of 3f as determined by SXRC.
Figure 3: Molecular structure and crystal packing of 5e as determined by SXRC.
Scheme 3: Proposed mechanism of the quinuclidine-mediated difluorination of 1,3-dicarbonyl substrates.
Scheme 4: Proposed mechanisms of carbonate and chloride ion-mediated difluorination of 1,3-dicarbonyl substra...
Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments
- Aissam Okba,
- Pablo Simón Marqués,
- Kyohei Matsuo,
- Naoki Aratani,
- Hiroko Yamada,
- Gwénaël Rapenne and
- Claire Kammerer
Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30
- bidimensional structures such as starphenes [34] from custom-made stable and soluble precursors. Interestingly, extrusion of CO from mono- or α-diketone precursors has also been achieved on metallic surfaces under ultra-high vacuum (UHV) conditions upon thermal annealing, photoirradiation or activation by the
Graphical Abstract
Scheme 1: “Precursor approach” for the synthesis of π-conjugated polycyclic compounds, with the thermally- or...
Scheme 2: Valence isomerization of chalcogen heteropines and subsequent cheletropic extrusion in the case of ...
Scheme 3: Early example of phenanthrene synthesis via a chemically-induced S-extrusion (and concomitant decar...
Scheme 4: Top: Conversion of dinaphthothiepine bisimides 3a,b and their sulfoxide analogues 4a,b into PBIs 6a,...
Figure 1: Top view (a) and side view (b) of the X-ray crystal structure of thiepine 3b showing its bent confo...
Scheme 5: Modular synthetic route towards dinaphthothiepines 3a–f and the corresponding S-oxides 4a–d, incorp...
Scheme 6: Top: Conversion of dithienobenzothiepine monomeric units into dithienonaphthalenes, upon S-extrusio...
Scheme 7: Synthesis of S-doped extended triphenylene derivative 22 from 3-bromothiophene (17) with the therma...
Scheme 8: Top: Synthesis of thermally-stable O-doped HBC 26a. Bottom: Synthesis of S- and Se-based soluble pr...
Scheme 9: Synthesis of dinaphthooxepine bisimide 33 and conversion into PBI 6f by O-extrusion triggered by el...
Figure 2: Cyclic voltammogram of dinaphthooxepine 33, evidencing the irreversibility of the reduction process...
Scheme 10: Top: Early example of 6-membered ring contraction with concomitant S-extrusion leading to dinaphtho...
Scheme 11: Examples of S-extrusion from annelated 1,2-dithiins under photoactivation (top) or thermal activati...
Scheme 12: Synthesis of dibenzo[1,4]dithiapentalene upon photoextrusion of SO2 [78].
Scheme 13: Extrusion of SO in naphthotrithiin-2-oxides for the synthesis of 2,5-dihydrothiophene 1-oxides [79].
Scheme 14: SO-extrusion as a key step in the synthesis of fullerenes (C60 and C70) encapsulating H2 molecules [80,82]....
Scheme 15: Synthesis of diepoxytetracene precursor 56 and its on-surface conversion into tetracene upon O-extr...
Scheme 16: Soluble precursors of hexacene, decacene and dodecacene incorporating 1,4-epoxides in their hydroca...
Scheme 17: Synthesis of tetraepoxide 59 as soluble precursor of decacene [85].
Figure 3: Constant-height STM measurement of decacene on Au(111) using a CO-functionalized tip (sample voltag...
1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF3: the case of alkyne hydration. Chemistry vs electrochemistry
- Marta David,
- Elisa Galli,
- Richard C. D. Brown,
- Marta Feroci,
- Fabrizio Vetica and
- Martina Bortolami
Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147
- alkyne group, in low yield (39%), with the majority of the starting alkyne being recovered (46%) (see Table S2, Supporting Information File 1). Increasing the amount of electrogenerated BF3 by applying 4 F/mol and extending the reaction time (5 h) reversed the selectivity in favour of the diketone 2jj
Graphical Abstract
Figure 1: Comparison of the hydration reactions of different alkynes in BMIm-BF4 catalysed by BF3·Et2O (blue)...
Scheme 1: Anodic oxidation of tetrafluoroborate anion.
