Search for "enantiomeric purity" in Full Text gives 75 result(s) in Beilstein Journal of Organic Chemistry.
Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104
Graphical Abstract
Figure 1: Representatives of biologically active 1,2-thiazoles.
Scheme 1: Synthesis of 2,5-dihydro-1,2-thiazoles.
Scheme 2: Synthesis of 2,3-dihydro-N-sulfonyl-1,2-thiazoles 3. Conditions: aMethod A: thioamide 1 (1.0 equiv)...
Figure 2: Compound 3aa in thermal ellipsoids 50% probability.
Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60
Figure 1: TreeMap chart of the top 15 Web of Science categories for 6,700 articles containing the keywords “a...
Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52
Graphical Abstract
Scheme 1: Previous work for obtaining different fluorinated amino acids and target fluorinated amino acids de...
Scheme 2: Synthesis of fluorinated aromatic amino acids 2 and 3.
Scheme 3: a) Gram-scale synthesis of fluorinated alkyl iodide precursor 10; b) Synthesis of trifluorinated le...
Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34
Graphical Abstract
Scheme 1: Previous work.
Scheme 2: Hypothesis, retro-Michael reaction, and its application in kinetic resolution.
Scheme 3: Model reaction.
Scheme 4: Kinetic resolution of the Michael adduct 1.
Scheme 5: Chemical correlation of 3 with 19.
Scheme 6: Epimerization of the anti-1 adduct promoted by A.
Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6
Graphical Abstract
Scheme 1: Formation of axially chiral styrenes 3 via iminium activation.
Scheme 2: Synthesis of axially chiral 2-arylquinolines 6.
Scheme 3: Atroposelective intramolecular (4 + 2) annulation leading to aryl-substituted indolines.
Scheme 4: Atroposelective formation of biaryl via twofold aldol condensation.
Scheme 5: Strategy towards diastereodivergent formation of axially chiral oligonaphthylenes.
Scheme 6: Atroposelective formation of chiral biaryls based on a Michael/Henry domino reaction.
Scheme 7: Organocatalytic Michael/aldol cascade followed by oxidative aromatization.
Scheme 8: Atroposelective formation of C(sp2)–C(sp3) axially chiral compounds.
Scheme 9: NHC-catalyzed synthesis of axially chiral styrenes 26.
Scheme 10: NHC-catalyzed synthesis of biaxial chiral pyranones.
Scheme 11: Formation of bridged biaryls with eight-membered lactones.
Scheme 12: The NHC-catalyzed (3 + 2) annulation of urazoles 37 and ynals 36.
Scheme 13: NHC-catalyzed synthesis of axially chiral 4‑aryl α‑carbolines 41.
Scheme 14: NHC-catalyzed construction of N–N-axially chiral pyrroles and indoles.
Scheme 15: NHC-catalyzed oxidative Michael–aldol cascade.
Scheme 16: NHC-catalyzed (4 + 2) annulation for the synthesis of benzothiophene-fused biaryls.
Scheme 17: NHC-catalyzed desymmetrization of N-aryl maleimides.
Scheme 18: NHC-catalyzed deracemization of biaryl hydroxy aldehydes 55a–k into axially chiral benzonitriles 56a...
Scheme 19: NHC-catalyzed desymmetrization of 2-aryloxyisophthalaldehydes.
Scheme 20: NHC-catalyzed DKR of 2-arylbenzaldehydes 62.
Scheme 21: Atroposelective biaryl amination.
Scheme 22: CPA-catalyzed atroposelective amination of 2-anilinonaphthalenes.
Scheme 23: Atroposelective DKR of naphthylindoles.
Scheme 24: CPA-catalyzed kinetic resolution of binaphthylamines.
Scheme 25: Atroposelective amination of aromatic amines with diazodicarboxylates.
Scheme 26: Atroposelective Friedländer heteroannulation.
Scheme 27: CPA-catalyzed formation of axially chiral 4-arylquinolines.
Scheme 28: CPA-catalyzed Friedländer reaction of arylketones with cyclohexanones.
Scheme 29: CPA-catalyzed atroposelective Povarov reaction.
Scheme 30: Atroposelective CPA-catalyzed Povarov reaction.
Scheme 31: Paal–Knorr formation of axially chiral N-pyrrolylindoles and N-pyrrolylpyrroles.
Scheme 32: Atroposelective Paal–Knorr reaction leading to N-pyrrolylpyrroles.
Scheme 33: Atroposelective Pictet–Spengler reaction of N-arylindoles with aldehydes.
Scheme 34: Atroposelective Pictet–Spengler reaction leading to tetrahydroisoquinolin-8-ylanilines.
Scheme 35: Atroposelective formation of arylindoles.
Scheme 36: CPA-catalyzed arylation of naphthoquinones with indolizines.
Scheme 37: Atroposelective reaction of o-naphthoquinones.
Scheme 38: CPA-catalyzed formation of axially chiral arylquinones.
Scheme 39: CPA-catalyzed axially chiral N-arylquinones.
Scheme 40: Atroposelective additions of bisindoles to isatin-based 3-indolylmethanols.
Scheme 41: CPA-catalyzed synthesis of axially chiral arylindolylindolinones.
Scheme 42: CPA-catalyzed reaction between bisindoles and ninhydrin-derived 3-indoylmethanols.
Scheme 43: Atroposelective reaction of bisindoles and isatin-derived imines.
Scheme 44: CPA-catalyzed formation of axially chiral bisindoles.
Scheme 45: Atroposelective reaction of 2-naphthols with alkynylhydroxyisoindolinones.
Scheme 46: CPA-catalyzed reaction of indolylnaphthols with propargylic alcohols.
Scheme 47: Atroposelective formation of indolylpyrroloindoles.
Scheme 48: Atroposelective reaction of indolylnaphthalenes with alkynylnaphthols.
Scheme 49: CPA-catalyzed addition of naphthols to alkynyl-2-naphthols and 2-naphthylamines.
Scheme 50: CPA-catalyzed formation of axially chiral aryl-alkene-indoles.
Scheme 51: CPA-catalyzed formation of axially chiral styrenes.
Scheme 52: Atroposelective formation of alkenylindoles.
Scheme 53: Atroposelective formation of axially chiral arylquinolines.
Scheme 54: Atroposelective (3 + 2) cycloaddition of alkynylindoles with azonaphthalenes.
Scheme 55: CPA-catalyzed formation of axially chiral 3-(1H-benzo[d]imidazol-2-yl)quinolines.
Scheme 56: Atroposelective cyclization of 3-(arylethynyl)-1H-indoles.
Scheme 57: Atroposelective three-component heteroannulation.
Scheme 58: CPA-catalyzed formation of arylbenzimidazols.
Scheme 59: CPA-catalyzed reaction of N-naphthylglycine esters with nitrosobenzenes.
Scheme 60: CPA-catalyzed formation of axially chiral N-arylbenzimidazoles.
Scheme 61: CPA-catalyzed formation of axially chiral arylbenzoindoles.
Scheme 62: CPA-catalyzed formation of pyrrolylnaphthalenes.
Scheme 63: CPA-catalyzed addition of naphthols and indoles to nitronaphthalenes.
Scheme 64: Atroposelective reaction of heterobiaryl aldehydes and aminobenzamides.
Scheme 65: Atroposelective cyclization forming N-arylquinolones.
Scheme 66: Atroposelective formation of 9H-carbazol-9-ylnaphthalenes and 1H-indol-1-ylnaphthalene.
Scheme 67: CPA-catalyzed formation of pyrazolylnaphthalenes.
Scheme 68: Atroposelective addition of diazodicarboxamides to azaborinephenols.
Scheme 69: Catalytic formation of axially chiral arylpyrroles.
Scheme 70: Atroposelective coupling of 1-azonaphthalenes with 2-naphthols.
Scheme 71: CPA-catalyzed formation of axially chiral oxindole-based styrenes.
Scheme 72: Atroposelective electrophilic bromination of aminonaphthoquinones.
Scheme 73: Atroposelective bromination of dienes.
Scheme 74: CPA-catalyzed formation of axially chiral 5-arylpyrimidines.
Scheme 75: Atroposelective hydrolysis of biaryloxazepines.
Scheme 76: Atroposelective opening of dinaphthosiloles.
Scheme 77: Atroposelective reduction of naphthylenals.
Scheme 78: Atroposelective allylic substitution with 2-naphthols.
Scheme 79: Atroposelective allylic alkylation with phosphinamides.
Scheme 80: Atroposelective allylic substitution with aminopyrroles.
Scheme 81: Atroposelective allylic substitution with aromatic sulfinamides.
Scheme 82: Atroposelective sulfonylation of naphthylynones.
Scheme 83: Squaramide-catalyzed reaction of alkynyl-2-naphthols with 5H-oxazolones.
Scheme 84: Formation of axially chiral styrenes via sulfonylative opening of cyclopropanols.
Scheme 85: Atroposelective organo-photocatalyzed sulfonylation of alkynyl-2-naphthols.
Scheme 86: Thiourea-catalyzed atroposelective cyclization of alkynylnaphthols.
Scheme 87: Squaramide-catalyzed formation of axially chiral naphthylisothiazoles.
Scheme 88: Atroposelective iodo-cyclization catalyzed by squaramide C69.
Scheme 89: Squaramide-catalyzed formation of axially chiral oligoarenes.
Scheme 90: Atroposelective ring-opening of cyclic N-sulfonylamides.
Scheme 91: Thiourea-catalyzed kinetic resolution of naphthylpyrroles.
Scheme 92: Atroposelective ring-opening of arylindole lactams.
Scheme 93: Atroposelective reaction of 1-naphthyl-2-tetralones and diarylphosphine oxides.
Scheme 94: Atroposelective reaction of iminoquinones with indoles.
Scheme 95: Kinetic resolution of binaphthylalcohols.
Scheme 96: DKR of hydroxynaphthylamides.
Scheme 97: Atroposelective N-alkylation with phase-transfer catalyst C75.
Scheme 98: Atroposelective allylic substitution via kinetic resolution of biarylsulfonamides.
Scheme 99: Atroposelective bromo-functionalization of alkynylarenes.
Scheme 100: Sulfenylation-induced atroposelective cyclization.
Scheme 101: Atroposelective O-sulfonylation of isochromenone-indoles.
Scheme 102: NHC-catalyzed atroposelective N-acylation of anilines.
Scheme 103: Peptide-catalyzed atroposelective ring-opening of lactones.
Scheme 104: Peptide-catalyzed coupling of 2-naphthols with quinones.
Scheme 105: Atroposelective nucleophilic aromatic substitution of fluoroarenes.
Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258
Graphical Abstract
Figure 1: Example bioactive compounds containing cyclic scaffolds potentially accessible by HVI chemistry.
Figure 2: A general mechanism for HVI-mediated endo- or exo-halocyclisation.
Scheme 1: Metal-free synthesis of β-fluorinated piperidines 6. Ts = tosyl.
Scheme 2: Intramolecular aminofluorination of unactivated alkenes with a palladium catalyst.
Scheme 3: Aminofluorination of alkenes in the synthesis of enantiomerically pure β-fluorinated piperidines. P...
Scheme 4: Synthesis of β-fluorinated piperidines.
Scheme 5: Intramolecular fluoroaminations of unsaturated amines published by Li.
Scheme 6: Intramolecular aminofluorination of unsaturated amines using 1-fluoro-3,3-dimethylbenziodoxole (12)...
Scheme 7: 3-fluoropyrrolidine synthesis. aDiastereomeric ratio (cis/trans) determined by 19F NMR analysis.
Scheme 8: Kitamura’s synthesis of 3-fluoropyrrolidines. Values in parentheses represent the cis:trans ratio.
Scheme 9: Jacobsen’s enantio- and diastereoselective protocol for the synthesis of syn-β-fluoroaziridines 15.
Scheme 10: Different HVI reagents lead to different diastereoselectivity in aminofluorination competing with c...
Scheme 11: Fluorocyclisation of unsaturated alcohols and carboxylic acids to make tetrahydrofurans, fluorometh...
Scheme 12: Oxyfluorination of unsaturated alcohols.
Scheme 13: Synthesis and mechanism of fluoro-benzoxazepines.
Scheme 14: Intramolecular fluorocyclisation of unsaturated carboxylic acids. Yield of isolated product within ...
Scheme 15: Synthesis of fluorinated tetrahydrofurans and butyrolactone.
Scheme 16: Synthesis of fluorinated oxazolines 32. aReaction time increased to 40 hours. Yields refer to isola...
Scheme 17: Electrochemical synthesis of fluorinated oxazolines.
Scheme 18: Electrochemical synthesis of chromanes.
Scheme 19: Synthesis of fluorinated oxazepanes.
Scheme 20: Enantioselective oxy-fluorination with a chiral aryliodide catayst.
Scheme 21: Catalytic synthesis of 5‑fluoro-2-aryloxazolines using BF3·Et2O as a source of fluoride and an acti...
Scheme 22: Intramolecular carbofluorination of alkenes.
Scheme 23: Intramolecular chlorocyclisation of unsaturated amines.
Scheme 24: Synthesis of chlorinated cyclic guanidines 44.
Scheme 25: Synthesis of chlorinated pyrido[2,3-b]indoles 46.
Scheme 26: Chlorolactonization and chloroetherification reactions.
Scheme 27: Proposed mechanism for the synthesis of chloromethyl oxazolines 49.
Scheme 28: Oxychlorination to form oxazine and oxazoline heterocycles promoted by BCl3.
Scheme 29: Aminobromocyclisation of homoallylic sulfonamides 53. The cis:trans ratios based on the 1H NMR of t...
Scheme 30: Synthesis of cyclic imines 45.
Scheme 31: Synthesis of brominated pyrrolo[2,3-b]indoles 59.
Scheme 32: Bromoamidation of alkenes.
Scheme 33: Synthesis of brominated cyclic guanidines 61 and 61’.
Scheme 34: Intramolecular bromocyclisation of N-oxyureas.
Scheme 35: The formation of 3-bromoindoles.
Scheme 36: Bromolactonisation of unsaturated acids 68.
Scheme 37: Synthesis of 5-bromomethyl-2-oxazolines.
Scheme 38: Synthesis of brominated chiral morpholines.
Scheme 39: Bromoenolcyclisation of unsaturated dicarbonyl groups.
Scheme 40: Brominated oxazines and oxazolines with BBr3.
Scheme 41: Synthesis of 5-bromomethtyl-2-phenylthiazoline.
Scheme 42: Intramolecular iodoamination of unsaturated amines.
Scheme 43: Formation of 3-iodoindoles.
Scheme 44: Iodoetherification of 2,2-diphenyl-4-penten-1-carboxylic acid (47’) and 2,2-diphenyl-4-penten-1-ol (...
Scheme 45: Synthesis of 5-iodomethyl-2-oxazolines.
Scheme 46: Synthesis of chiral iodinated morpholines. aFrom the ʟ-form of the amino acid starting material. Th...
Scheme 47: Iodoenolcyclisation of unsaturated dicarbonyl compounds 74.
Scheme 48: Synthesis of 5-iodomethtyl-2-phenylthiazoline (87).
Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168
Graphical Abstract
Scheme 1: Known and improved synthetic strategies to access α-(hetero)aryl-amino acids.
Scheme 2: Reformatsky reagent production.
Scheme 3: Scope of ethyl heteroarylacetates. Isolated yields are given. *Dark reactions were carried out for ...
Scheme 4: Telescoped flow synthesis of heteroarylacetates.
Scheme 5: Potential routes for the preparation of oximes.
Scheme 6: Oxime group insertion step.
Scheme 7: Amino ester production: general scheme, scope and gram scale experiment. The numbers in brackets re...
Scheme 8: Reactions scheme and results for the on-DNA experiments. The reported values represent the normaliz...
Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62
Graphical Abstract
Scheme 1: The preparation of 5-isopropyl-5-methyl-2-(pyridin-2-yl)imidazolidin-4-one derivatives and their ap...
Figure 1: The structure of newly designed ligands I–IV.
Figure 2: Plausible transition structures for the Henry reaction.
Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102
Graphical Abstract
Scheme 1: In situ generation of imidazolylidene carbene.
Scheme 2: Hg(II) complex of NHC.
Scheme 3: Isolable and bottlable carbene reported by Arduengo [3].
Scheme 4: First air-stable carbene synthesized by Arduengo in 1992 [5].
Figure 1: General structure of an NHC.
Figure 2: Stabilization of an NHC by donation of the lone pair electrons into the vacant p-orbital (LUMO) at ...
Figure 3: Abnormal NHC reported by Bertrand [8,9].
Figure 4: Cu(d) orbital to σ*C-N(NHC) interactions in NHC–CuX complexes computed at the B3LYP/def2-SVP level ...
Figure 5: Molecular orbital contributions to the NHC–metal bond.
Scheme 5: Synthesis of NHC–Cu(I) complexes by deprotonation of NHC precursors with a base.
Scheme 6: Synthesis of [NHC–CuX] complexes.
Scheme 7: Synthesis of [(ICy)CuX] and [(It-Bu)CuX] complexes.
Scheme 8: Synthesis of iodido-bridged copper–NHC complexes by deprotonation of benzimidazolium salts reported...
Scheme 9: Synthesis of copper complexes by deprotonation of triazolium salts.
Scheme 10: Synthesis of thiazolylidene–Cu(I) complex by deprotonation with KOt-Bu.
Scheme 11: Preparation of NHC–Cu(I) complexes.
Scheme 12: Synthesis of methylmalonic acid-derived anionic [(26a,b)CuCl]Li(THF)2 and zwitterionic (28) heterol...
Scheme 13: Synthesis of diaminocarbene and diamidocarbene (DAC)–Cu(I) complexes.
Scheme 14: Synthesis of the cationic (NHC)2Cu(I) complex 39 from benzimidazolium salts 38 with tetrakis(aceton...
Scheme 15: Synthesis of NHC and ADC (acyclic diamino carbenes) Cu(I) hexamethyldisilazide complexes reported b...
Scheme 16: Synthesis of NHC–copper(I) complexes using an acetylacetonate-functionalized imidazolium zwitterion...
Scheme 17: Synthesis of NHC–Cu(I) complexes through deprotonation of azolium salts with Cu2O.
Scheme 18: Synthesis of NHC–CuBr complex through deprotonation with Cu2O reported by Kolychev [31].
Scheme 19: Synthesis of chiral NHC–CuBr complexes from phenoxyimine-imidazolium salts reported by Douthwaite a...
Scheme 20: Preparation of linear neutral NHC–CuCl complexes through the use of Cu2O. For abbreviations, please...
Scheme 21: Synthesis of abnormal-NHC–copper(I) complexes by Bertrand, Cazin and co-workers [35].
Scheme 22: Microwave-assisted synthesis of thiazolylidene/benzothiazolylidene–CuBr complexes by Bansal and co-...
Scheme 23: Synthesis of NHC–CuX complexes through transmetallation.
Scheme 24: Preparation of six- or seven-membered NHC–Cu(I) complexes through transmetalation from Ag(I) comple...
Scheme 25: Synthesis of 1,2,3-triazolylidene–CuCl complexes through transmetallation of Ag(I) complexes genera...
Scheme 26: Synthesis of NHC–copper complexes having both Cu(I) and Cu(II) units through transmetalation report...
Scheme 27: Synthesis of new [(IPr(CH2)3Si(OiPr)3)CuX] complexes and anchoring on MCM-41.
Scheme 28: Synthesis of bis(trimethylsilyl)phosphide–Cu(I)–NHC complexes through ligand displacement.
Scheme 29: Synthesis of silyl- and stannyl [(NHC)Cu−ER3] complexes.
Scheme 30: Synthesis of amido-, phenolato-, thiophenolato–Cu(NHC) complexes.
Scheme 31: Synthesis of first isolable NHC–Cu–difluoromethyl complexes reported by Sanford et al. [44].
Scheme 32: Synthesis of NHC–Cu(I)–bifluoride complexes reported by Riant, Leyssens and co-workers [45].
Scheme 33: Conjugate addition of Et2Zn to enones catalyzed by an NHC–Cu(I) complex reported by Woodward in 200...
Scheme 34: Hydrosilylation of a carbonyl group.
Scheme 35: NHC–Cu(I)-catalyzed hydrosilylation of ketones reported by Nolan et al. [48,49].
Scheme 36: Application of chiral NHC–CuCl complex 104 for the enantioselective hydrosilylation of ketones.
Scheme 37: Hydrosilylation reactions catalyzed by NHC–Cu(Ot-Bu) complexes.
Scheme 38: NHC–CuCl catalyzed carbonylative silylation of alkyl halides.
Scheme 39: Nucleophilic conjugate addition to an activated C=C bond.
Figure 6: Molecular electrostatic potential maps (MESP) of two NHC–CuX complexes computed at the B3LYP/def2-S...
Scheme 40: Conjugate addition of Grignard reagents to 3-alkyl-substituted cyclohexenones catalyzed by a chiral...
Scheme 41: NHC–copper complex-catalyzed conjugate addition of Grignard reagent to 3-substituted hexenone repor...
Scheme 42: Conjugate addition or organoaluminum reagents to β-substituted cyclic enones.
Scheme 43: Conjugate addition of boronates to acyclic α,β-unsaturated carboxylic esters, ketones, and thioeste...
Scheme 44: NHC–Cu(I)-catalyzed hydroboration of an allene reported by Hoveyda [63].
Scheme 45: Conjugate addition of Et2Zn to cyclohexenone catalyzed by NHC–Cu(I) complex derived from benzimidaz...
Scheme 46: Asymmetric conjugate addition of diethylzinc to 3-nonen-2-one catalyzed by NHC–Cu complexes derived...
Scheme 47: General scheme of a [3 + 2] cycloaddition reaction.
Scheme 48: [3 + 2] Cycloaddition of azides with alkynes catalyzed by NHC–Cu(I) complexes reported by Diez-Gonz...
Scheme 49: Application of NHC–CuCl/N-donor combination to catalyze the [3 + 2] cycloaddition of benzyl azide w...
Scheme 50: [3 + 2] Cycloaddition of azides with acetylenes catalyzed by bis(NHC)–Cu complex 131 and mixed NHC–...
Figure 7: NHC–CuCl complex 133 as catalyst for the [3 + 2] cycloaddition of alkynes with azides at room tempe...
Scheme 51: [3 + 2] Cycloaddition of a bulky azide with an alkynylpyridine using [(NHC)Cu(μ-I)2Cu(NHC)] copper ...
Scheme 52: [3 + 2] Cycloaddition of benzyl azide with phenylacetylene under homogeneous and heterogeneous cata...
Scheme 53: [3 + 2] Cycloaddition of benzyl azide with acetylenes catalyzed by bisthiazolylidene dicopper(I) co...
Figure 8: Copper (I)–NHC linear coordination polymer 137 and its conversion into tetranuclear (138) and dinuc...
Scheme 54: An A3 reaction.
Scheme 55: Synthesis of SiO2-immobilized NHC–Cu(I) catalyst 141 and its application in the A3-coupling reactio...
Scheme 56: Preparation of dual-purpose Ru@SiO2–[(NHC)CuCl] catalyst system 142 developed by Bordet, Leitner an...
Scheme 57: Application of the catalyst system Ru@SiO2–[Cu(NHC)] 142 to the one-pot tandem A3 reaction and hydr...
Scheme 58: A3 reaction of phenylacetylene with secondary amines and aldehydes catalyzed by benzothiazolylidene...
Figure 9: Kohn–Sham HOMOs of phenylacetylene and NHC–Cu(I)–phenylacetylene complex computed at the B3LYP/def2...
Figure 10: Energies of the FMOs of phenylacetylene, iminium ion, and NHC–Cu(I)–phenylacetylene complex compute...
Scheme 59: NHC–Cu(I) catalyzed diboration of ketones 147 by reacting with bis(pinacolato)diboron (148) reporte...
Scheme 60: Protoboration of terminal allenes catalyzed by NHC–Cu(I) complexes reported by Hoveyda and co-worke...
Scheme 61: NHC–CuCl-catalyzed borylation of α-alkoxyallenes to give 2-boryl-1,3-butadienes.
Scheme 62: Regioselective hydroborylation of propargylic alcohols and ethers catalyzed by NHC–CuCl complexes 1...
Scheme 63: NHC–CuOt-Bu-catalyzed semihydrogenation and hydroborylation of alkynes.
Scheme 64: Enantioselective NHC–Cu(I)-catalyzed hydroborations of 1,1-disubstituted aryl olefins reported by H...
Scheme 65: Enantioselective NHC–Cu(I)-catalyzed hydroboration of exocyclic 1,1-disubstituted alkenes reported ...
Scheme 66: Markovnikov-selective NHC–CuOH-catalyzed hydroboration of alkenes and alkynes reported by Jones et ...
Scheme 67: Dehydrogenative borylation and silylation of styrenes catalyzed by NHC–CuOt-Bu complexes developed ...
Scheme 68: N–H/C(sp2)–H carboxylation catalyzed by NHC–CuOH complexes.
Scheme 69: C–H Carboxylation of benzoxazole and benzothiazole derivatives with CO2 using a 1,2,3-triazol-5-yli...
Scheme 70: Use of Cu(I) complex derived from diethylene glycol-functionalized imidazo[1,5,a] pyridin-3-ylidene...
Scheme 71: Allylation and alkenylation of polyfluoroarenes and heteroarenes catalyzed by NHC–Cu(I) complexes r...
Scheme 72: Enantioselective C(sp2)–H allylation of (benz)oxazoles and benzothiazoles with γ,γ-disubstituted pr...
Scheme 73: C(sp2)–H arylation of arenes catalyzed by dual NHC–Cu/NHC–Pd catalytic system.
Scheme 74: C(sp2)–H Amidation of (hetero)arenes with N-chlorocarbamates/N-chloro-N-sodiocarbamates catalyzed b...
Scheme 75: NHC–CuI catalyzed thiolation of benzothiazoles and benzoxazoles.
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31
Graphical Abstract
Figure 1: Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolide...
Scheme 1: Biosynthetic pathway proposed by Pettit and co-workers.
Scheme 2: Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-...
Scheme 3: Retrosynthetic approaches.
Scheme 4: Attempt of total synthesis of 2 by Boger and co-workers employing the Mitsunobu approach [27].
Scheme 5: Total synthesis of combretastatin D-2 (2) reported by Boger and co-workers employing an intramolecu...
Scheme 6: Formal synthesis of combretastatin D-2 (2) by Deshpande and co-workers using the Mitsunobu conditio...
Scheme 7: Total synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 8: Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 9: Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41].
Scheme 10: Synthesis of fragment 57 by Couladouros and co-workers [43,45].
Scheme 11: Formal synthesis of compound 2 by Couladouros and co-workers [43,45].
Scheme 12: Synthesis of fragment 66 by Couladouros and co-workers [44,45].
Scheme 13: Synthesis of fragment 70 by Couladouros and co-workers [44,45].
Scheme 14: Synthesis of fragment 77 by Couladouros and co-workers [44,45].
Scheme 15: Synthesis of combretastatins 1 and 2 by Couladouros and co-workers [44,45].
Scheme 16: Formal synthesis of compound 2 by Gangakhedkar and co-workers [48].
Scheme 17: Synthesis of fragment 14 by Cousin and co-workers [50].
Scheme 18: Synthesis of fragment 91 by Cousin and co-workers [50].
Scheme 19: Formal synthesis of compound 2 by Cousin and co-workers [50].
Scheme 20: Synthesis of 2 diolide by Cousin and co-workers [50].
Scheme 21: Synthesis of combretastatin D-4 (4) by Nishiyama and co-workers [54].
Scheme 22: Synthesis of fragment 112 by Pettit and co-workers [55].
Scheme 23: Synthesis of fragment 114 by Pettit and co-workers [55].
Scheme 24: Attempt to the synthesis of compound 2 by Pettit and co-workers [55].
Scheme 25: Synthesis of combretastatin-D2 (2) starting from isovanilin (80) by Pettit and co-workers [55].
Scheme 26: Attempted synthesis of combretastatin-D2 (2) derivatives through an SNAr approach [55].
Scheme 27: Synthesis of combretastatin D-4 (4) by Pettit and co-workers [55].
Scheme 28: Synthesis of combretastatin D-2 (2) by Harras and co-workers [57].
Scheme 29: Synthesis of combretastatin D-4 (4) by Harras and co-workers [57].
Scheme 30: Formal synthesis of combretastatin D-1 (1) by Harras and co-workers [57].
Scheme 31: Synthesis of 11-O-methylcorniculatolide A (5) by Raut and co-workers [69].
Scheme 32: Synthesis of isocorniculatolide A (7) and O-methylated isocorniculatolide A 8 by Raut and co-worker...
Scheme 33: Synthesis of isocorniculatolide B (10) and hydroxyisocorniculatolide B 175 by Kim and co-workers [71].
Scheme 34: Synthesis of compound 9, 178, and 11 by Kim and co-workers [71].
Scheme 35: Synthesis of combretastatin D-2 prodrug salts [55].
Figure 2: ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (appr...
Figure 3: IC50 of compounds against α-glucosidase [19].
Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82
Graphical Abstract
Scheme 1: Biosynthesis of 2-MIB (1). A) Naturally observed pathway through methylation of GPP to 2-Me-GPP by ...
Figure 1: A) Active site of 2MIBS with the bound substrate surrogate 2FGPP (generated with Pymol from the cry...
Scheme 2: Synthesis of (R)- and (S)-2-Me-LPP.
Figure 2: Structures of 2MIBS side products and spontaneous degradation products of 2-Me-LPP. The enantiomers...
Figure 3: Total ion chromatograms of extracts from an incubation of A) enantiomerically pure (R)-2-Me-LPP wit...
Scheme 3: Hypothetical mechanism for the isomerization of (S)-2-Me-LPP through 2-Me-GPP to (R)-2-Me-LPP.
Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46
Graphical Abstract
Figure 1: The structure of the oxazolidine-2-one-containing drugs linezolid (1) and rivaroxaban (2).
Figure 2: Overview of the chiral ligands that were used for the study of the asymmetric Henry reaction.
Scheme 1: Syntheses of aldehydes 15–20.
Scheme 2: Synthesis of linezolid (1) and rivaroxaban (2) from nitroaldols 24 or 26.
Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18
Graphical Abstract
Figure 1: Model of the catalyst action.
Figure 2: Catalysts screened.
Scheme 1: Screening of different N-protecting groups. Reaction conditions: 0.2 M solution of 1 (1 equiv), 2 (...
Scheme 2: Scope of the reaction (the relative configuration of the major diastereoisomer is depicted). Reacti...
Scheme 3: Comparison reactions of E- and Z-isomers (the relative configurations of the major diastereoisomers...
Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11
Graphical Abstract
Figure 1: Examples of amino-functionalized 1,2-oxazole derivatives I–VIII.
Scheme 1: Conversion of cyclic amino acids to 1,2-oxazole derivatives.
Scheme 2: Plausible mechanisms for the formation of 1,2-oxazoles 4a–h and VII from β-enamino ketoesters 3a–h ...
Figure 2: (a) 1H NMR (italics), 13C NMR (normal), and 15N NMR (bold) chemical shifts (ppm) of compound 3a in ...
Scheme 3: Synthesis of compound 15N-1,2-oxazole 5. The coupling constants of JHN and JCN from 15N2 are indica...
Figure 3: Stacked chromatogram view of pairs of enantiomers with area, %: (R)-4b, ee 100% (tR = 10.1 min) and...
Figure 4: (a) Structure of 4b with syn- and anti-conformers; (b) superimposed 1H NMR and 1D gradient NOE spec...
Scheme 4: Synthesis of 2-[4-(methoxycarbonyl)-1,2-oxazol-5-yl]cycloaminyl-1-ium trifluoroacetates 6a,b.
Figure 5: ORTEP diagram of the asymmetric unit consisting of two cations 6b(A) and 6b(B) and triflate anions.
Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176
Graphical Abstract
Figure 1: Catalyst design principles.
Scheme 1: Synthesis of isothiocyanate 3a and isocyanate 3b.
Scheme 2: Synthesis of sulfinylthioureas C1 and ureas C2.
Scheme 3: Synthesis of adducts 8a,d,f in solution.
Figure 2: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) structures of catalyst (S,R) and (S,S)-C2, en...
Figure 3: a) Arrangements of reactants in the transition states; b) DFT-calculated (PBEh-3c/def2-SV(P)//M06-2...
Figure 4: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) reaction profile for the Michael addition of ...
Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160
Graphical Abstract
Figure 1: Synthetic strategies employing chiral Brønsted acid catalysis.
Scheme 1: The substrate scope of the aminalization reaction for different aldehydes. aAfter recrystallization...
Scheme 2: The substrate scope of the intermolecular aminalization reaction for anthranilamide derivatives. aA...
Figure 2: X-ray single-crystal structure of aminal 3l with the displacement ellipsoids drawn at the 30% proba...
Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32
Graphical Abstract
Figure 1: Stabilizing interaction in the CF3CH2+ carbenium ion (top) and structure of the first observable fl...
Scheme 1: Isodesmic equations accounting for the destabilizing effect of the CF3 group. ΔE in kcal⋅mol−1, cal...
Scheme 2: Stabilizing effect of fluorine atoms by resonance electron donation in carbenium ions (δ in ppm).
Scheme 3: Direct in situ NMR observation of α-(trifluoromethyl)carbenium ion or protonated alcohols. Δδ = δ19...
Scheme 4: Reported 13C NMR chemical shifts for the α-(trifluoromethyl)carbenium ion 10c (δ in ppm).
Scheme 5: Direct NMR observation of α-(trifluoromethyl)carbenium ions in situ (δ in ppm).
Scheme 6: Illustration of the ion pair solvolysis mechanism for sulfonate 13f. YOH = solvent.
Figure 2: Solvolysis rate for 13a–i and 17.
Figure 3: Structures of allyl triflates 18 and 19 and allyl brosylate 20. Bs = p-BrC6H4SO2.
Figure 4: Structure of tosylate derivatives 21.
Figure 5: a) Structure of triflate derivatives 22. b) Stereochemistry outcomes of the reaction starting from (...
Scheme 7: Solvolysis reaction of naphthalene and anthracenyl derivatives 26 and 29.
Figure 6: Structure of bisarylated derivatives 34.
Figure 7: Structure of bisarylated derivatives 36.
Scheme 8: Reactivity of 9c in the presence of a Brønsted acid.
Scheme 9: Cationic electrocyclization of 38a–c under strongly acidic conditions.
Scheme 10: Brønsted acid-catalyzed synthesis of indenes 42 and indanes 43.
Scheme 11: Reactivity of sulfurane 44 in triflic acid.
Scheme 12: Solvolysis of triflate 45f in alcoholic solvents.
Scheme 13: Synthesis of labeled 18O-52.
Scheme 14: Reactivity of sulfurane 53 in triflic acid.
Figure 8: Structure of tosylates 56 and 21f.
Scheme 15: Resonance forms in benzylic carbenium ions.
Figure 9: Structure of pyrrole derivatives 58 and 59.
Scheme 16: Resonance structure 60↔60’.
Scheme 17: Ga(OTf)3-catalyzed synthesis of 3,3’- and 3,6’-bis(indolyl)methane from trifluoromethylated 3-indol...
Scheme 18: Proposed reaction mechanism.
Scheme 19: Metal-free 1,2-phosphorylation of 3-indolylmethanols.
Scheme 20: Superacid-mediated arylation of thiophene derivatives.
Scheme 21: In situ mechanistic NMR investigations.
Scheme 22: Proposed mechanisms for the prenyltransferase-catalyzed condensation.
Scheme 23: Influence of a CF3 group on the allylic SN1- and SN2-mechanism-based reactions.
Scheme 24: Influence of the CF3 group on the condensation reaction.
Scheme 25: Solvolysis of 90 in TFE.
Scheme 26: Solvolysis of allyl triflates 94 and 97 and isomerization attempt of 96.
Scheme 27: Proposed mechanism for the formation of 95.
Scheme 28: Formation of α-(trifluoromethyl)allylcarbenium ion 100 in a superacid.
Scheme 29: Lewis acid activation of CF3-substituted allylic alcohols.
Scheme 30: Bimetallic-cluster-stabilized α-(trifluoromethyl)carbenium ions.
Scheme 31: Reactivity of cluster-stabilized α-(trifluoromethyl)carbenium ions.
Scheme 32: α-(Trifluoromethyl)propargylium ion 122↔122’ generated from silyl ether 120 in a superacid.
Scheme 33: Formation of α-(trifluoromethyl)propargylium ions from CF3-substituted propargyl alcohols.
Scheme 34: Direct NMR observation of the protonation of some trifluoromethyl ketones in situ and the correspon...
Scheme 35: Selected resonance forms in protonated fluoroketone derivatives.
Scheme 36: Acid-catalyzed Friedel–Crafts reactions of trifluoromethyl ketones 143a,b and 147a–c.
Scheme 37: Enantioselective hydroarylation of CF3-substituted ketones.
Scheme 38: Acid-catalyzed arylation of ketones 152a–c.
Scheme 39: Reactivity of 156 in a superacid.
Scheme 40: Reactivity of α-CF3-substituted heteroaromatic ketones and alcohols as well as 1,3-diketones.
Scheme 41: Reactivity of 168 with benzene in the presence of a Lewis or Brønsted acid.
Scheme 42: Acid-catalyzed three-component asymmetric reaction.
Scheme 43: Anodic oxidation of amines 178a–c and proposed mechanism.
Scheme 44: Reactivity of 179b in the presence of a strong Lewis acid.
Scheme 45: Trifluoromethylated derivatives as precursors of trifluoromethylated iminium ions.
Scheme 46: Mannich reaction with trifluoromethylated hemiaminal 189.
Scheme 47: Suitable nucleophiles reacting with 192 after Lewis acid activation.
Scheme 48: Strecker reaction involving the trifluoromethylated iminium ion 187.
Scheme 49: Reactivity of 199 toward nucleophiles.
Scheme 50: Reactivity of 204a with benzene in the presence of a Lewis acid.
Scheme 51: Reactivity of α-(trifluoromethyl)-α-chloro sulfides in the presence of strong Lewis acids.
Scheme 52: Anodic oxidation of sulfides 213a–h and Pummerer rearrangement.
Scheme 53: Mechanism for the electrochemical oxidation of the sulfide 213a.
Scheme 54: Reactivity of (trifluoromethyl)diazomethane (217a) in HSO3F.
Figure 10: a) Structure of diazoalkanes 217a–c and b) rate-limiting steps of their decomposition.
Scheme 55: Deamination reaction of racemic 221 and enantioenriched (S)-221.
Scheme 56: Deamination reaction of labeled 221-d2. Elimination products were formed in this reaction, the yiel...
Scheme 57: Deamination reaction of 225-d2. Elimination products were also formed in this reaction in undetermi...
Scheme 58: Formation of 229 from 228 via 1,2-H-shift.
Scheme 59: Deamination reaction of 230. Elimination products were formed in this reaction, the yield of which ...
Scheme 60: Deamination of several diazonium ions. Elimination products were formed in these reactions, the yie...
Scheme 61: Solvolysis reaction mechanism of alkyl tosylates.
Scheme 62: Solvolysis outcome for the tosylates 248 and 249 in HSO3FSbF5.
Figure 11: Solvolysis rate of 248, 249, 252, and 253 in 91% H2SO4.
Scheme 63: Illustration of the reaction pathways. TsCl, pyridine, −5 °C (A); 98% H2SO4, 30 °C (B); 98% H2SO4, ...
Scheme 64: Proposed solvolysis mechanism for the aliphatic tosylate 248.
Scheme 65: Solvolysis of the derivatives 259 and 260.
Scheme 66: Solvolysis of triflate 261. SOH = solvent.
Scheme 67: Intramolecular Friedel–Crafts alkylations upon the solvolysis of triflates 264 and 267.
Scheme 68: α-CF3-enhanced γ-silyl elimination of cyclobutyltosylates 270a,b.
Scheme 69: γ-Silyl elimination in the synthesis of a large variety of CF3-substituted cyclopropanes. Pf = pent...
Scheme 70: Synthetic pathways to 281. aNMR yields.
Scheme 71: The cyclopropyl-substituted homoallylcyclobutylcarbenium ion manifold.
Scheme 72: Reactivity of CF3-substituted cyclopropylcarbinyl derivatives 287a–c. LG = leaving group.
Scheme 73: Reactivity of CF3-substituted cyclopropylcarbinyl derivatives 291a–c.
Scheme 74: Superacid-promoted dimerization or TFP.
Scheme 75: Reactivity of TFP in a superacid.
Scheme 76: gem-Difluorination of α-fluoroalkyl styrenes via the formation of a “hidden” α-RF-substituted carbe...
Scheme 77: Solvolysis of CF3-substituted pentyne 307.
Scheme 78: Photochemical rearrangement of 313.
Figure 12: Structure of 2-norbornylcarbenium ion 318 and argued model for the stabilization of this cation.
Figure 13: Structures and solvolysis rate (TFE, 25 °C) of the sulfonates 319–321. Mos = p-MeOC6H4SO2.
Scheme 79: Mechanism for the solvolysis of 323. SOH = solvent.
Scheme 80: Products formed by the hydrolysis of 328.
Scheme 81: Proposed carbenium ion intermediates in an equilibrium during the solvolysis of tosylates 328, 333,...
Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4
Graphical Abstract
Figure 1: Homotropane (azabicyclononane) systems.
Figure 2: Alkaloids (−)-adaline (1), (+)-euphococcinine (2) and (+)-N-methyleuphococcinine (3).
Scheme 1: Synthetic strategies before 1995.
Scheme 2: Synthesis (±)-adaline (1) and (±)-euphococcinine (2). Reagents and conditions: i) 1. dihydropyran, ...
Scheme 3: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) H2O2, SeO2 (cat), acetone, rt, 88%; i...
Scheme 4: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) 2,4-bis(4-phenoxyphenyl)-1,3-dithia-2...
Scheme 5: Synthesis of (±)-euphococcinine precursor (±)-42. Reagents and conditions: i) Bu3SnH, AIBN, toluene...
Scheme 6: Synthesis of (−)-adaline (1). Reagents and conditions: i) LiH2NBH3, THF, 40 °C, 88%; ii) TPAP, NMO,...
Scheme 7: Synthesis of (−)-adaline (1) and (−)-euphococcinine (2). Reagents and conditions: i) 1. BuLi, t-BuO...
Scheme 8: Synthesis of (−)-adaline (1). Reagents and conditions: i) Ref. [52]; ii) Et3N, TBDMSOTf, CH2Cl2, 0 °C t...
Scheme 9: Synthesis of (+)-euphococcinine (2). Reagents and conditions: i) 1. Cp2ZrCl2,AlMe3, CH2Cl2; 2. p-me...
Scheme 10: Synthesis of (−)-adaline 1. Reagents and conditions: i) 1. CuBr.DMS, Et2O/DMS, -42 ºC; 2. 1-heptyne...
Scheme 11: Synthesis of (−)-euphococcinine (2) and (−)-adaline (1). Reagents and conditions: i) 102, KHMDS, Et2...
Scheme 12: Synthesis of N-methyleuphococcinine 3. Reagents and conditions: i) 108 (1.5 equiv), 3,5-di-F-C6H3B(...
Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162
Graphical Abstract
Figure 1: Chemical structures of hexa-acylated Escherichia coli lipid A, monophosphorylated lipid X (the redu...
Scheme 1: Enantioselective synthesis of Nap-protected (R)-3-hydroxytetradecanoic acid (7). Conditions: (a) Me...
Scheme 2: Synthesis of monoacylated glucosamine building blocks. Conditions: (a) NaHCO3, TrocCl, H2O, 0 °C, 9...
Scheme 3: Synthesis of lipid X monosaccharide 1. Conditions: (a) Zn, AcOH, CH2Cl2, rt; (b) acid 7, EDC·HCl, D...
Scheme 4: Synthesis of the disaccharide lipid A precursor 2. Conditions: (a) TfOH, 4 Å MS, dry CH2Cl2, 94%; (...
Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91
Graphical Abstract
Figure 1: Categories I–V of fluorinated phenylalanines.
Scheme 1: Synthesis of fluorinated phenylalanines via Jackson’s method.
Scheme 2: Synthesis of all-cis-tetrafluorocyclohexylphenylalanines.
Scheme 3: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine (nPt: neopentyl, TCE: trichloroethyl).
Scheme 4: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine derivatives 17.
Scheme 5: Synthesis of fluorinated Phe analogues from Cbz-protected aminomalonates.
Scheme 6: Synthesis of tetrafluorophenylalanine analogues via the 3-methyl-4-imidazolidinone auxiliary 25.
Scheme 7: Synthesis of tetrafluoro-Phe derivatives via chiral auxiliary 31.
Scheme 8: Synthesis of 2,5-difluoro-Phe and 2,4,5-trifluoro-Phe via Schöllkopf reagent 34.
Scheme 9: Synthesis of 2-fluoro- and 2,6-difluoro Fmoc-Phe derivatives starting from chiral auxiliary 39.
Scheme 10: Synthesis of 2-[18F]FPhe via chiral auxiliary 43.
Scheme 11: Synthesis of FPhe 49a via photooxidative cyanation.
Scheme 12: Synthesis of FPhe derivatives via Erlenmeyer azalactone synthesis.
Scheme 13: Synthesis of (R)- and (S)-2,5-difluoro Phe via the azalactone method.
Scheme 14: Synthesis of 3-bromo-4-fluoro-(S)-Phe (65).
Scheme 15: Synthesis of [18F]FPhe via radiofluorination of phenylalanine with [18F]F2 or [18F]AcOF.
Scheme 16: Synthesis of 4-borono-2-[18F]FPhe.
Scheme 17: Synthesis of protected 4-[18F]FPhe via arylstannane derivatives.
Scheme 18: Synthesis of FPhe derivatives via intermediate imine formation.
Scheme 19: Synthesis of FPhe derivatives via Knoevenagel condensation.
Scheme 20: Synthesis of FPhe derivatives 88a,b from aspartic acid derivatives.
Scheme 21: Synthesis of 2-(2-fluoroethyl)phenylalanine derivatives 93 and 95.
Scheme 22: Synthesis of FPhe derivatives via Zn2+ complexes.
Scheme 23: Synthesis of FPhe derivatives via Ni2+ complexes.
Scheme 24: Synthesis of 3,4,5-trifluorophenylalanine hydrochloride (109).
Scheme 25: Synthesis of FPhe derivatives via phenylalanine aminomutase (PAM).
Scheme 26: Synthesis of (R)-2,5-difluorophenylalanine 115.
Scheme 27: Synthesis of β-fluorophenylalanine via 2-amino-1,3-diol derivatives.
Scheme 28: Synthesis of β-fluorophenylalanine derivatives via the oxazolidinone chiral auxiliary 122.
Scheme 29: Synthesis of β-fluorophenylalanine from pyruvate hemiketal 130.
Scheme 30: Synthesis of β-fluorophenylalanine (136) via fluorination of β-hydroxyphenylalanine (137).
Scheme 31: Synthesis of β-fluorophenylalanine from aziridine derivatives.
Scheme 32: Synthesis of β-fluorophenylalanine 136 via direct fluorination of pyruvate esters.
Scheme 33: Synthesis of β-fluorophenylalanine via fluorination of ethyl 3-phenylpyruvate enol using DAST.
Scheme 34: Synthesis of β-fluorophenylalanine derivatives using photosensitizer TCB.
Scheme 35: Synthesis of β-fluorophenylalanine derivatives using Selectflour and dibenzosuberenone.
Scheme 36: Synthesis of protected β-fluorophenylalanine via aziridinium intermediate 150.
Scheme 37: Synthesis of β-fluorophenylalanine derivatives via fluorination of α-hydroxy-β-aminophenylalanine d...
Scheme 38: Synthesis of β-fluorophenylalanine derivatives from α- or β-hydroxy esters 152a and 155.
Scheme 39: Synthesis of a series of β-fluoro-Phe derivatives via Pd-catalyzed direct fluorination of β-methyle...
Scheme 40: Synthesis of series of β-fluorinated Phe derivatives using quinoline-based ligand 162 in the Pd-cat...
Scheme 41: Synthesis of β,β-difluorophenylalanine derivatives from 2,2-difluoroacetaldehyde derivatives 164a,b....
Scheme 42: Synthesis of β,β-difluorophenylalanine derivatives via an imine chiral auxiliary.
Scheme 43: Synthesis of α-fluorophenylalanine derivatives via direct fluorination of protected Phe 174.
Figure 2: Structures of PET radiotracers of 18FPhe derivatives.
Figure 3: Structures of melfufen (179) and melphalan (180) anticancer drugs.
Figure 4: Structure of gastrazole (JB95008, 181), a CCK2 receptor antagonist.
Figure 5: Dual CCK1/CCK2 antagonist 182.
Figure 6: Structure of sitagliptin (183), an antidiabetic drug.
Figure 7: Structure of retaglpitin (184) and antidiabetic drug.
Figure 8: Structure of evogliptin (185), an antidiabetic drug.
Figure 9: Structure of LY2497282 (186) a DPP-4 inhibitor for the treatment of type II diabetes.
Figure 10: Structure of ulimorelin (187).
Figure 11: Structure of GLP1R (188).
Figure 12: Structures of Nav1.7 blockers 189 and 190.
Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90
Graphical Abstract
Scheme 1: Copper-catalysed ACA of organometallics to piperidones. A) addition of organozinc reagents; B) addi...
Scheme 2: Copper-catalysed ACA of alkenylalanes to N-substituted-2,3-dehydro-4-piperidones.
Scheme 3: Copper-catalysed asymmetric addition of dialkylzinc reagents to N-acyl-4-methoxypyridinium salts fo...
Scheme 4: Copper-catalysed ACA of organozirconium reagents to N-substituted 2,3-dehydro-4-piperidones and lac...
Scheme 5: Copper-catalysed ACA of Grignard reagents to chromones and coumarins and further derivatisation of ...
Scheme 6: Copper-catalysed ACA of Grignard reagents to N-protected quinolones.
Scheme 7: Copper-catalysed ACAs of organometallics to conjugated unsaturated lactams.
Scheme 8: Copper-catalysed ACA of Et2Zn to 5,6-dihydro-2-pyranone.
Scheme 9: Copper-catalysed ACA of Grignard reagents to pyranone and 5,6-dihydro-2-pyranone.
Scheme 10: Copper-catalysed AAA of an organozirconium reagent to heterocyclic acceptors.
Scheme 11: Copper-catalysed ring opening of an oxygen-bridged substrate with trialkylaluminium reagents.
Scheme 12: Copper-catalysed ring opening of oxabicyclic substrates with organolithium reagents (selected examp...
Scheme 13: Copper-catalysed ring opening of polycyclic meso hydrazines.
Scheme 14: Copper-catalysed ACA of Grignard reagents to alkenyl-substituted aromatic N-heterocycles.
Scheme 15: Copper-catalysed ACA of Grignard reagents to β-substituted alkenylpyridines.
Scheme 16: Copper-catalysed ACA of organozinc reagents to alkylidene Meldrum’s acids.
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
Graphical Abstract
Scheme 1: Intramolecular (A) and intermolecular (B) enyne metathesis reactions.
Scheme 2: Ene–yne and yne–ene mechanisms for intramolecular enyne metathesis reactions.
Scheme 3: Metallacarbene mechanism in intermolecular enyne metathesis.
Scheme 4: The Oguri strategy for accessing artemisinin analogs 1a–c through enyne metathesis.
Scheme 5: Access to the tetracyclic core of nanolobatolide (2) via tandem enyne metathesis followed by an Eu(...
Scheme 6: Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step.
Scheme 7: Synthesis of amphidinolide K (4) by an enyne metathesis route.
Scheme 8: Trost synthesis of des-epoxy-amphidinolide N (5) [72].
Scheme 9: Enyne metathesis between the propargylic derivative and the allylic alcohol in the synthesis of the...
Scheme 10: Synthetic route to amphidinolide N (6a).
Scheme 11: Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closi...
Scheme 12: Synthesis of the anthramycin precursor 8 from ʟ-methionine by a tandem enyne metathesis–cross metat...
Scheme 13: Synthesis of (−)‐clavukerin A (9) and (−)‐isoclavukerin A (10) by an enyne metathesis route startin...
Scheme 14: Synthesis of (−)-isoguaiene (11) through an enyne metathesis as the key step.
Scheme 15: Synthesis of erogorgiaene (12) by a tandem enyne metathesis/cross metathesis sequence using the sec...
Scheme 16: Synthesis of (−)-galanthamine (13) from isovanilin by an enyne metathesis.
Scheme 17: Application of enyne metathesis for the synthesis of kempene diterpenes 14a–c.
Scheme 18: Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis.
Scheme 19: Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.
Scheme 20: Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions.
Scheme 21: Total synthesis of (−)-flueggine A (18) and (+)-virosaine B (19) from Weinreb amide by enyne metath...
Scheme 22: Access to virgidivarine (20) and virgiboidine (21) by an enyne metathesis route.
Scheme 23: Enyne metathesis approach to (−)-zenkequinone B (22).
Scheme 24: Access to C-aryl glycoside 23 by an intermolecular enyne metathesis/Diels–Alder cycloaddition.
Scheme 25: Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reac...
Scheme 26: Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94].
Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57
Graphical Abstract
Scheme 1: Retrosynthesis of (+)-disparlure (1), (−)-disparlure (3), (+)-monachalure (2), and (−)-monachalure (...
Scheme 2: Isomerization of trans-2,3-butanediacetals 9–11 to cis-2,3-butanediacetals 12–14.
Scheme 3: Synthesis of diol 17 and its subsequent modifications.
Scheme 4: Synthesis of (+)-disparlure (1) and (+)-monachalure (2).
Scheme 5: Synthesis of (−)-disparlure (3) and (−)-monachalure (4).
Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32
Graphical Abstract
Scheme 1: Synthesis of BBFZPys through the Pd-catalyzed C–H/C–H coupling.
Scheme 2: Synthesis of 3a–c.
Scheme 3: Synthesis of 4a–c through oxidative coupling reaction.
Scheme 4: Synthesis of 6.
Figure 1: Absorption (dotted line) and fluorescence (solid line) spectra of 3, 4, and 6 measured as CHCl3 sol...
Figure 2: CD and CPL spectra of 3 measured as CHCl3 solutions (1.0 × 10−5 M) and in the solid states (dispers...
Figure 3: CD and CPL spectra of 4 and 6 measured as CHCl3 solutions (1.0 × 10−5 M) and in solid states (dispe...
Figure 4: ORTEP drawings of 4b and 4c with 50% thermal probability. Hydrogen atoms and solvent molecules are ...
Figure 5: Intramolecular stacking structures of 4b and 4c.