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Search for "electrophilic substitution" in Full Text gives 66 result(s) in Beilstein Journal of Organic Chemistry.
The design and synthesis of an antibacterial phenothiazine–siderophore conjugate
- Abed Tarapdar,
- James K. S. Norris,
- Oliver Sampson,
- Galina Mukamolova and
- James T. Hodgkinson
Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242
- . In the final PMB global deprotection step we were pleased to observe the formation of our desired final phenothiazine–sideophore conjugate in moderate yield. The addition of anisole to the reaction mixture was found to be essential to inhibit competing electrophilic substitution side reactions. A
Graphical Abstract
Figure 1: NDH-2 is a validated target for 1 with an MIC of 1.1 µg/mL against M. tuberculosis.
Scheme 1: Synthesis of phenothiazine-PEG-amine component.
Scheme 2: Synthesis of the azotochelin siderophore component.
Scheme 3: Final conjugation and deprotection to yield a phenothiazine siderophore conjugate.
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
- Michael K. Bogdos,
- Emmanuel Pinard and
- John A. Murphy
Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179
- regioselective and follows the same substitution pattern as the electrophilic substitution of electron-rich heterocycles. Although highly elaborated structures are not presented, the mild reaction conditions and general functional group compatibility that the reaction exhibits make it well suited for LSF
Graphical Abstract
Figure 1: Depiction of the energy levels of a typical organic molecule and the photophysical processes it can...
Figure 2: General catalytic cycle of a photocatalyst in a photoredox organocatalysed reaction. [cat] – photoc...
Figure 3: Structures and names of the most common photocatalysts encountered in the reviewed literature.
Figure 4: General example of a reductive quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocata...
Figure 5: General example of an oxidative quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocat...
Scheme 1: Oxidative coupling of aldehydes and amines to amides using acridinium salt photocatalysis.
Figure 6: Biologically active molecules containing a benzamide linkage.
Scheme 2: The photocatalytic reduction of amino acids to produce the corresponding free or protected amines.
Scheme 3: The organocatalysed photoredox base-mediated oxidation of thiols to disulfides.
Scheme 4: C-Terminal modification of peptides and proteins using organophotoredox catalysis.
Scheme 5: The reduction and aryl coupling of aryl halides using a doubly excited photocatalyst (PDI).
Figure 7: Mechanism for the coupling of aryl halides using PDI, which is excited sequentially by two photons.
Scheme 6: The arylation of five-membered heteroarenes using arenediazonium salts under organophotoredox condi...
Scheme 7: The C–H (hetero)arylation of five-membered heterocycles under Eosin Y photocatalysis.
Scheme 8: The C–H sulfurisation of imidazoheterocycles using Eosin B-catalyzed photochemical methods.
Scheme 9: The introduction of the thiocyanate group using Eosin Y photocatalysis.
Scheme 10: Sulfonamidation of pyrroles using oxygen as the terminal oxidant.
Scheme 11: DDQ-catalysed C–H amination of arenes and heteroarenes.
Scheme 12: Photoredox-promoted radical Michael addition reactions of allylic or benzylic carbons.
Figure 8: Proposed mechanistic rationale for the observed chemoselectivities.
Scheme 13: The photocatalytic manipulation of C–H bonds adjacent to amine groups.
Scheme 14: The perylene-catalysed organophotoredox tandem difluoromethylation–acetamidation of styrene-type al...
Figure 9: Examples of biologically active molecules containing highly functionalised five membered heterocycl...
Scheme 15: The [3 + 2]-cycloaddition leading to the formation of pyrroles, through the reaction of 2H-azirines...
Figure 10: Proposed intermediate that determines the regioselectivity of the reaction.
Figure 11: Comparison of possible pathways of reaction and various intermediates involved.
Scheme 16: The acridinium salt-catalysed formation of oxazoles from aldehydes and 2H-azirines.
Scheme 17: The synthesis of oxazolines and thiazolines from amides and thioamides using organocatalysed photor...
Figure 12: Biologically active molecules on the market containing 1,3,4-oxadiazole moieties.
Scheme 18: The synthesis of 1,3,4-oxadiazoles from aldehyde semicarbazones using Eosin Y organophotocatalysis.
Scheme 19: The dimerization of primary thioamides to 1,2,4-thiadiazoles catalysed by the presence of Eosin Y a...
Scheme 20: The radical cycloaddition of o-methylthioarenediazonium salts and substituted alkynes towards the f...
Scheme 21: The dehydrogenative cascade reaction for the synthesis of 5,6-benzofused heterocyclic systems.
Figure 13: Trifluoromethylated version of compounds which have known biological activities.
Scheme 22: Eosin Y-catalysed photoredox formation of 3-substituted benzimidazoles.
Scheme 23: Oxidation of dihydropyrimidines by atmospheric oxygen using photoredox catalysis.
Scheme 24: Photoredox-organocatalysed transformation of 2-substituted phenolic imines to benzoxazoles.
Scheme 25: Visible light-driven oxidative annulation of arylamidines.
Scheme 26: Methylene blue-photocatalysed direct C–H trifluoromethylation of heterocycles.
Scheme 27: Photoredox hydrotrifluoromethylation of terminal alkenes and alkynes.
Scheme 28: Trifluoromethylation and perfluoroalkylation of aromatics and heteroaromatics.
Scheme 29: The cooperative asymmetric and photoredox catalysis towards the functionalisation of α-amino sp3 C–...
Scheme 30: Organophotoredox-catalysed direct C–H amidation of aromatics.
Scheme 31: Direct C–H alkylation of heterocycles using BF3K salts. CFL – compact fluorescent lamp.
Figure 14: The modification of camptothecin, demonstrating the use of the Molander protocol in LSF.
Scheme 32: Direct C–H amination of aromatics using acridinium salts.
Scheme 33: Photoredox-catalysed nucleophilic aromatic substitution of nucleophiles onto methoxybenzene derivat...
Scheme 34: The direct C–H cyanation of aromatics with a focus on its use for LSF.
Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical
- Santhivardhana Reddy Yetra,
- Zhigao Shen,
- Hui Wang and
- Lutz Ackermann
Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131
- preferentially, which can be rationalized with a base-assisted internal electrophilic substitution (BIES) [24][105] C–H cobaltation mechanism. In addition, the electron-rich amidating reagent 2c was found to be inherently more reactive (Scheme 5). As to further late-stage manipulation of the thus-obtained
Graphical Abstract
Figure 1: Selected ferrocene-based ligands and organocatalysts.
Scheme 1: Scope of substituted dioxazolones 2.
Scheme 2: C–H Amidation of arylated ferrocenes 1.
Scheme 3: Thiocarbonyl-assisted C–H amidation.
Scheme 4: H/D Exchange reactions.
Scheme 5: Intermolecular competition experiments.
Scheme 6: Synthesis of aminoketone 4aa.
Scheme 7: Mechanochemical ferrocene C–H nitrogenation.
One hundred years of benzotropone chemistry
- Arif Dastan,
- Haydar Kilic and
- Nurullah Saracoglu
Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98
Graphical Abstract
Scheme 1: Tropone (1), tropolone (2) and their resonance structures.
Figure 1: Natural products containing a tropone nucleus.
Figure 2: Possible isomers 11–13 of benzotropone.
Scheme 2: Synthesis of benzotropones 11 and 12.
Scheme 3: Oxidation products of benzotropylium fluoroborate (16).
Scheme 4: Oxidation of 7-bromo-5H-benzo[7]annulene (22).
Scheme 5: Synthesis of 4,5-benzotropone (11) using o-phthalaldehyde (27).
Scheme 6: Synthesis of 4,5-benzotropone (11) starting from oxobenzonorbornadiene 31.
Scheme 7: Acid-catalyzed cleavage of oxo-bridge of 34.
Scheme 8: Synthesis of 4,5-benzotropone (11) from o-xylylene dibromide (38).
Scheme 9: Synthesis of 4,5-benzotropone (11) via the carbene adduct 41.
Scheme 10: Heck coupling strategy for the synthesis of 11.
Scheme 11: Synthesis of benzofulvalenes via carbonyl group of 4,5-benzotropone (11).
Figure 3: Some cycloheptatrienylium cations.
Scheme 12: Synthesis of condensation product 63 and its subsequent oxidative cyclization products.
Figure 4: A novel series of benzo[7]annulenes prepared from 4,5-benzotropone (11).
Scheme 13: Preparation of substituted benzo[7]annulene 72 using the Mukaiyama-Michael reaction.
Figure 5: Possible benzo[7]annulenylidenes 73–75.
Scheme 14: Thermal and photochemical decomposition of 7-diazo-7H-benzo[7]annulene (76) and the trapping of int...
Scheme 15: Synthesis of benzoheptafulvalene 86.
Scheme 16: Synthesis of 7-(diphenylmethylene)-7H-benzo[7]annulene (89).
Scheme 17: Reaction of 4,5-benzotropone (11) with dimethyl diazomethane.
Scheme 18: Synthesis of dihydrobenzomethoxyazocine 103.
Scheme 19: Synthesis and reducibility of benzo-homo-2-methoxyazocines.
Scheme 20: Synthesis of 4,5-benzohomotropones 104 and 115 from 4,5-benzotropones 11 and 113.
Scheme 21: A catalytic deuterogenation of 4,5-benzotropone (11) and synthesis of 5-monosubstituted benzo[7]ann...
Scheme 22: Synthesis of methyl benzo[7]annulenes 131 and 132.
Scheme 23: Ambident reactivity of halobenzo[7]annulenylium cations 133a/b.
Scheme 24: Preparation of benzo[7]annulenylidene–iron complexes 147.
Scheme 25: Synthesis of 1-ethynylbenzotropone (150) and the etheric compound 152 from 4,5-benzotropone (11) wi...
Scheme 26: Thermal decomposition of 4,5-benzotropone (11).
Scheme 27: Reaction of 4,5-benzotropone (11) with 1,2-ethanediol and 1,2-ethanedithiol.
Scheme 28: Conversions of 1-benzosuberone (162) to 2,3-benzotropone (12).
Scheme 29: Synthesis strategies for 2,3-bezotropone (12) using 1-benzosuberones.
Scheme 30: Oxidation-based synthesis of 2,3-benzotropone (12) via 1-benzosuberone (162).
Scheme 31: Synthesis of 2,3-benzotropone (12) from α-tetralone (171) via ring-expansion.
Scheme 32: Preparation of 2,3-benzotropone (12) by using of benzotropolone 174.
Figure 6: Benzoheptafulvenes as condensation products of 2,3-benzotropone (12).
Scheme 33: Conversion of 2,3-benzotropone (12) to tosylhydrazone salt 182 and gem-dichloride 187.
Figure 7: Benzohomoazocines 191–193 and benzoazocines 194–197.
Scheme 34: From 2,3-benzotropone (12) to carbonium ions 198–201.
Scheme 35: Cycloaddition reactions of 2,3-benzotropone (12).
Scheme 36: Reaction of 2,3-benzotropone (12) with various reagents and compounds.
Figure 8: 3,4-Benzotropone (13) and its resonance structure.
Scheme 37: Synthesis of 6,7-benzobicyclo[3.2.0]hepta-3,6-dien-2-one (230).
Figure 9: Photolysis and thermolysis products of 230.
Figure 10: Benzotropolones and their tautomeric structures.
Scheme 38: Synthesis strategies of 4,5-benzotropolone (238).
Scheme 39: Synthesis protocol for 2-hydroxy-4,5-benzotropone (238) using oxazole-benzo[7]annulene 247.
Figure 11: Some quinoxaline and pyrazine derivatives 254–256 prepared from 4,5-benzotropolone (238).
Scheme 40: Nitration product of 4,5-benzotropolone (238) and its isomerization to 1-nitro-naphthoic acid (259)....
Scheme 41: Synthesis protocol for 6-hydroxy-2,3-benzotropone (239) from benzosuberone (162).
Scheme 42: Various reactions via 6-hydroxy-2,3-benzotropone (239).
Scheme 43: Photoreaction of 6-hydroxy-2,3-benzotropone (239).
Scheme 44: Synthesis of 7-hydroxy-2,3-benzotropone (241) from benzosuberone (162).
Scheme 45: Synthesis strategy for 7-hydroxy-2,3-benzotropone (241) from ketone 276.
Scheme 46: Synthesis of 7-hydroxy-2,3-benzotropone (241) from β-naphthoquinone (280).
Scheme 47: Synthesis of 7-hydroxy-2,3-benzotropone (241) from bicyclic endoperoxide 213.
Scheme 48: Synthesis of 7-hydroxy-2,3-benzotropone (241) by ring-closing metathesis.
Figure 12: Various monosubstitution products 289–291 of 7-hydroxy-2,3-benzotropone (241).
Scheme 49: Reaction of 7-hydroxy-2,3-benzotropone (241) with various reagents.
Scheme 50: Synthesis of 4-hydroxy-2,3-benzotropones 174 and 304 from diketones 300/301.
Scheme 51: Catalytic hydrogenation of diketones 300 and 174.
Scheme 52: Synthesis of halo-benzotropones from alkoxy-naphthalenes 306, 307 and 310.
Figure 13: Unexpected byproducts 313–315 during synthesis of chlorobenzotropone 309.
Figure 14: Some halobenzotropones and their cycloadducts.
Scheme 53: Multisep synthesis of 2-chlorobenzotropone 309.
Scheme 54: A multistep synthesis of 2-bromo-benzotropone 26.
Scheme 55: A multistep synthesis of bromo-2,3-benzotropones 311 and 316.
Scheme 56: Oxidation reactions of 8-bromo-5H-benzo[7]annulene (329) with some oxidants.
Scheme 57: Synthesis of 2-bromo-4,5-benzotropone (26).
Scheme 58: Synthesis of 6-chloro-2,3-benzotropone (335) using LiCl and proposed intermediate 336.
Scheme 59: Reaction of 7-bromo-2,3-benzotropone (316) with methylamine.
Scheme 60: Reactions of bromo-2,3-benzotropones 26 and 311 with dimethylamine.
Scheme 61: Reactions of bromobenzotropones 311 and 26 with NaOMe.
Scheme 62: Reactions of bromobenzotropones 26 and 312 with t-BuOK in the presence of DPIBF.
Scheme 63: Cobalt-catalyzed reductive cross-couplings of 7-bromo-2,3-benzotropone (316) with cyclic α-bromo en...
Figure 15: Cycloadduct 357 and its di-π-methane rearrangement product 358.
Scheme 64: Catalytic hydrogenation of 2-chloro-4,5-benzotropone (311).
Scheme 65: Synthesis of dibromo-benzotropones from benzotropones.
Scheme 66: Bromination/dehydrobromination of benzosuberone (162).
Scheme 67: Some transformations of isomeric dibromo-benzotropones 261A/B.
Scheme 68: Transformations of benzotropolone 239B to halobenzotropolones 369–371.
Figure 16: Bromobenzotropolones 372–376 and 290 prepared via bromination/dehydrobromination strategy.
Scheme 69: Synthesis of some halobenzotropolones 289, 377 and 378.
Figure 17: Bromo-chloro-derivatives 379–381 prepared via chlorination.
Scheme 70: Synthesis of 7-iodo-3,4-benzotropolone (382).
Scheme 71: Hydrogenation of bromobenzotropolones 369 and 370.
Scheme 72: Debromination reactions of mono- and dibromides 290 and 375.
Figure 18: Nitratation and oxidation products of some halobenzotropolenes.
Scheme 73: Azo-coupling reactions of some halobenzotropolones 294, 375 and 378.
Figure 19: Four possible isomers of dibenzotropones 396–399.
Figure 20: Resonance structures of tribenzotropone (400).
Scheme 74: Two synthetic pathways for tribenzotropone (400).
Scheme 75: Synthesis of tribenzotropone (400) from dibenzotropone 399.
Scheme 76: Synthesis of tribenzotropone (400) from 9,10-phenanthraquinone (406).
Scheme 77: Synthesis of tribenzotropone (400) from trifluoromethyl-substituted arene 411.
Figure 21: Dibenzosuberone (414).
Figure 22: Reduction products 415 and 416 of tribenzotropone (400).
Figure 23: Structures of tribenzotropone dimethyl ketal 417 and 4-phenylfluorenone (412) and proposed intermed...
Figure 24: Structures of benzylidene- and methylene-9H-tribenzo[a,c,e][7]annulenes 419 and 420 and chiral phos...
Figure 25: Structures of tetracyclic alcohol 422, p-quinone methide 423 and cation 424.
Figure 26: Structures of host molecules 425–427.
Scheme 78: Synthesis of non-helical overcrowded derivatives syn/anti-431.
Figure 27: Hexabenzooctalene 432.
Figure 28: Structures of possible eight isomers 433–440 of naphthotropone.
Scheme 79: Synthesis of naphthotropone 437 starting from 1-phenylcycloheptene (441).
Scheme 80: Synthesis of 10-hydroxy-11H-cyclohepta[a]naphthalen-11-one (448) from diester 445.
Scheme 81: Synthesis of naphthotropone 433.
Scheme 82: Synthesis of naphthotropones 433 and 434 via cycloaddition reaction.
Scheme 83: Synthesis of naphthotropone 434 starting from 452.
Figure 29: Structures of tricarbonyl(tropone)irons 458, and possible cycloadducts 459.
Scheme 84: Synthesis of naphthotropone 436.
Scheme 85: Synthesis of precursor 465 for naphthotropone 435.
Scheme 86: Generation of naphthotropone 435 from 465.
Figure 30: Structures of tropylium cations 469 and 470.
Figure 31: Structures of tropylium ions 471+.BF4−, 472+.BF4−, and 473+.BF4−.
Scheme 87: Synthesis of tropylium ions 471+.BF4− and 479+.ClO4−.
Scheme 88: Synthesis of 1- and 2-methylanthracene (481 and 482) via carbene–carbene rearrangement.
Figure 32: Trapping products 488–490.
Scheme 89: Generation and chemistry of a naphthoannelated cycloheptatrienylidene-cycloheptatetraene intermedia...
Scheme 90: Proposed intermediates and reaction pathways for adduct 498.
Scheme 91: Exited-state intramolecular proton transfer of 505.
Figure 33: Benzoditropones 506 and 507.
Scheme 92: Synthesis of benzoditropone 506e.
Scheme 93: Synthetic approaches for dibenzotropone 507 via tropone (1).
Scheme 94: Formation mechanisms of benzoditropone 507 and 516 via 515.
Scheme 95: Synthesis of benzoditropones 525 and 526 from pyromellitic dianhydride (527).
Figure 34: Possible three benzocyclobutatropones 534–536.
Scheme 96: Synthesis of benzocyclobutatropones 534 and 539.
Scheme 97: Synthesis attempts for benzocyclobutatropone 545.
Scheme 98: Generation and trapping of symmetric benzocyclobutatropone 536.
Scheme 99: Synthesis of chloro-benzocyclobutatropone 552 and proposed mechanism of fluorenone derivatives.
Scheme 100: Synthesis of tropolone analogue 559.
Scheme 101: Synthesis of tropolones 561 and 562.
Figure 35: o/p-Tropoquinone rings (563 and 564) and benzotropoquinones (565–567).
Scheme 102: Synthesis of benzotropoquinone 566.
Scheme 103: Synthesis of benzotropoquinone 567 via a Diels–Alder reaction.
Figure 36: Products 575–577 through 1,2,3-benzotropoquinone hydrate 569.
Scheme 104: Structures 578–582 prepared from tropoquinone 567.
Figure 37: Two possible structures 583 and 584 for dibenzotropoquinone, and precursor compound 585 for 583.
Scheme 105: Synthesis of saddle-shaped ketone 592 using dibenzotropoquinone 584.
Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups
- Cyrus Mowdawalla,
- Faiz Ahmed,
- Tian Li,
- Kiet Pham,
- Loma Dave,
- Grace Kim and
- I. F. Dempsey Hyatt
Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91
- -guided electrophilic substitution (HIGES). Keywords: electrophilic aromatic substitution; hypernucleofugality; hypervalent iodine; iodonio-Claisen; transmetallation; Introduction Hypervalent iodine compounds have been known for over a hundred years, but it was not until their renaissance in the 1990’s
- hypervalent iodine-guided electrophilic substitution (HIGES) reaction were performed by varying the hypervalent iodine starting material, the activator, the solvent, and the temperature at which the activated hypervalent iodine reagent formed (Table 1). Varying the temperature at 25 °C, 0 °C, and −50 °C did
- in an electrophilic substitution on the transmetallated benzyl hypervalent iodine intermediate. If such a stepwise mechanism were to occur then one would expect to see an additional coupling product. Based on the evidence provided by these crossover reactions it rules out such a stepwise reaction
Graphical Abstract
Scheme 1: Examples of the reductive iodonio-Claisen rearrangement compared to new reactivity seen with benzyl...
Scheme 2: Crossover reaction experiments.
Scheme 3: Suggested mechanism based on product formation and crossover experiments.
Scheme 4: Proposed mechanism for the generation of 2i from Table 2, entry 8.
Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective
- Yaroslav D. Boyko,
- Valentin S. Dorokhov,
- Alexey Yu. Sukhorukov and
- Sema L. Ioffe
Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220
- suggest that the [4 + 2]-cycloaddition process (2) is thermodynamically favored for nitrosoalkenes bearing electron-donating group R, whereas the presence of an electron withdrawing group at the same position promotes the electrophilic substitution pathway (1). Pinho e Melo and co-workers developed a one
Graphical Abstract
Scheme 1: Precursors of nitrosoalkenes NSA.
Scheme 2: Reactions of cyclic α-chlorooximes 1 with 1,3-dicarbonyl compounds.
Scheme 3: C-C-coupling of N,N-bis(silyloxy)enamines 3 with 1,3-dicarbonyl compounds.
Scheme 4: Reaction of N,N-bis(silyloxy)enamines 3 with nitronate anions.
Scheme 5: Reaction of α-chlorooximes TBS ethers 2 with ester enolates.
Scheme 6: Assembly of bicyclooctanone 14 via an intramolecular cyclization of nitrosoalkene NSA2.
Scheme 7: A general strategy for the assembly of bicyclo[2.2.1]heptanes via an intramolecular cyclization of ...
Scheme 8: Stereochemistry of Michael addition to cyclic nitrosoalkene NSA3.
Scheme 9: Stereochemistry of Michael addition to acyclic nitrosoalkenes NSA4.
Scheme 10: Stereochemistry of Michael addition to γ-alkoxy nitrosoalkene NSA5.
Scheme 11: Oppolzer’s total synthesis of 3-methoxy-9β-estra(1,3,5(10))trien(11,17)dione (25).
Scheme 12: Oppolzer’s total synthesis of (+/−)-isocomene.
Figure 1: Alkaloids synthesized using stereoselective Michael addition to conjugated nitrosoalkenes.
Scheme 13: Weinreb’s total synthesis of alstilobanines A, E and angustilodine.
Scheme 14: Weinreb’s approach to the core structure of apparicine alkaloids.
Scheme 15: Weinreb’s synthesis of (+/−)-myrioneurinol via stereoselective conjugate addition of malonate to ni...
Scheme 16: Reactions of cyclic α-chloro oximes with Grignard reagents.
Scheme 17: Corey’s synthesis of (+/−)-perhydrohistrionicotoxin.
Scheme 18: Addition of Gilman’s reagents to α,β-epoxy oximes 53.
Scheme 19: Addition of Gilman’s reagents to α-chlorooximes.
Scheme 20: Reaction of silyl nitronate 58 with organolithium reagents via nitrosoalkene NSA12.
Scheme 21: Reaction of β-ketoxime sulfones 61 and 63 with lithium acetylides.
Scheme 22: Electrophilic addition of nitrosoalkenes NSA14 to electron-rich arenes.
Scheme 23: Addition of nitrosoalkenes NSA14 to pyrroles and indoles.
Scheme 24: Reaction of phosphinyl nitrosoalkenes NSA15 with indole.
Scheme 25: Reaction of pyrrole with α,α’-dihalooximes 70.
Scheme 26: Synthesis of indole-derived psammaplin A analogue 72.
Scheme 27: Synthesis of tryptophanes by reduction of oximinoalkylated indoles 68.
Scheme 28: Ottenheijm’s synthesis of neoechinulin B analogue 77.
Scheme 29: Synthesis of 1,2-dihydropyrrolizinones 82 via addition of pyrrole to ethyl bromopyruvate oxime.
Scheme 30: Kozikowski’s strategy to indolactam-based alkaloids via addition of indoles to ethyl bromopyruvate ...
Scheme 31: Addition of cyanide anion to nitrosoalkenes and subsequent cyclization to 5-aminoisoxazoles 86.
Scheme 32: Et3N-catalysed addition of trimethylsilyl cyanide to N,N-bis(silyloxy)enamines 3 leading to 5-amino...
Scheme 33: Addition of TMSCN to allenyl N-siloxysulfonamide 89.
Scheme 34: Reaction of nitrosoallenes NSA16 with malodinitrile and ethyl cyanoacetic ester.
Scheme 35: [4 + 1]-Annulation of nitrosoalkenes NSA with sulfonium ylides 92.
Scheme 36: Reaction of diazo compounds 96 with nitrosoalkenes NSA.
Scheme 37: Tandem Michael addition/oxidative cyclization strategy to isoxazolines 100.
New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties
- Daria G. Selivanova,
- Alexei A. Gorbunov,
- Olga A. Mayorova,
- Alexander N. Vasyanin,
- Igor V. Lunegov,
- Elena V. Shklyaeva and
- Georgii G. Abashev
Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158
- mobility. Carbazole undergoes electrophilic substitution mainly at C3 or C6 positions to give 3(6)-substituted derivatives. Nevertheless, nowadays some new synthetic procedures [3][5][6][7] have given the opportunity to prepare conjugated systems which include 1,8-, 2,7- or 9(3)-carbazolylene units. The
Graphical Abstract
Scheme 1: Synthesis of 9-[ω-(methoxyphenoxy)alkyl]-9H-carbazoles 1a,b.
Scheme 2: Synthesis of 9-[ω-(4-methoxyphenoxy)alkyl]-9H-carbazole-3-carbaldehydes 2a,b and 1-(5-arylthiophen-...
Scheme 3: Synthesis of quadrupolar chromophores 6a,b−8a,b.
Figure 1: Comparison of UV–vis absorption and fluorescence spectra of compounds 2a–5a (a) and 2b–5b (b) in CH...
Figure 2: Comparison of UV–vis absorption and fluorescence spectra of compounds 6a (a, b), 6b (c, d) in vario...
Figure 3: Comparison of UV–vis absorption and fluorescence spectra of compounds 7a (a, b) and 7b (c, d) in va...
Figure 4: Correlation between Kamlet–Taft π* parameters [29] and the absorption and emission maxima wavelength of...
Figure 5: Comparison of UV–vis absorption spectra of 2-amino-4,6-di(4-bromophenyl)pyrimidine and 2-amino-4-[4...
Figure 6: UV–vis absorption and fluorescence spectra of compounds 8a (a), 8b ( b) in CHCl3 (c = 10−4 mol L−1)....
Figure 7: Cyclic voltammograms of compounds 2b (a), 5b (b); WE – carbon-pyroceramic electrode, 10 cycles, Et4...
Figure 8: Cyclic voltammograms of compounds 6b (a), 7b (b), 8b (с); WE – carbon-pyroceramic electrode, 10 cyc...
Nitration of 5,11-dihydroindolo[3,2-b]carbazoles and synthetic applications of their nitro-substituted derivatives
- Roman A. Irgashev,
- Nikita A. Kazin,
- Gennady L. Rusinov and
- Valery N. Charushin
Beilstein J. Org. Chem. 2017, 13, 1396–1406, doi:10.3762/bjoc.13.136
- as one more example of electrophilic substitution in this series of scaffolds. In general, nitration of aromatic compounds, one of the well-known reactions, has a great significance for various fields of industrial chemistry, as it has been exploited extensively for large-scale processes, obtaining
- electrophilic substitution can occur in electron-rich (hetero)aromatic substituents of compounds 1 as a side reaction. In this relation, we have focused our efforts on finding suitable conditions for nitration of these compounds in order to incorporate nitro groups exclusively at C-2 and C-8, avoid side
- 6,12-dinitro-ICZs 9 are susceptible to electrophilic substitution at their terminal benzene rings, we have investigated bromination and formylation of derivatives 9a,b, and our hopes for regioselectivity of these reactions have proved to be justified. In particular, aldehydes 12a,b have been obtained
Graphical Abstract
Figure 1: ICZ-cored materials for organic electronic devices.
Figure 2: General positions for SEAr in ICZs 1.
Scheme 1: Double nitration of indolo[3,2-b]carbazole 1a.
Figure 3: X-ray single crystal structure of compound 2a. Thermal ellipsoids of 50% probability are presented.
Scheme 2: C2- and C2,8-nitration of indolo[3,2-b]carbazoles 1.
Scheme 3: Reduction of nitro-substituted ICZs 2 and 3.
Scheme 4: Nitration of 6,12-unsubstituted indolo[3,2-b]carbazoles 8.
Figure 4: X-ray single crystal structure of compounds 9b and 10b. Thermal ellipsoids of 50% probability are p...
Scheme 5: Modification of 6,12-dinitro-ICZs 9a,b by electrophilic substitution.
Figure 5: X-ray single crystal structure of compounds 12b and 13b. Thermal ellipsoids of 50% probability are ...
Scheme 6: A possible mechanism for the reduction of 6,12-dinitro-ICZs 9a and 13a.
Scheme 7: Reactions of 6-nitro- and 6,12-dinitro-ICZs with S-nucleophiles.
Scheme 8: Successive substitution of nitro groups in 6,12-dinitro-ICZ 9a with N- and S-nucleophiles.
Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates
- Anna Wrona-Piotrowicz,
- Marzena Witalewska,
- Janusz Zakrzewski and
- Anna Makal
Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102
- .) [1][2][3][4][5][6][7]. Since 1 is an electron-rich arene, aromatic electrophilic substitution seems to be the simplest method for this purpose, and a plethora of substituted pyrenes have been synthesized in this way [1]. As is shown in Figure 1, the most reactive in such reactions are positions 1, 3
Graphical Abstract
Figure 1: Sites of electrophilic attack in 1 and 2.
Scheme 1: Triflic acid promoted reaction of 2 with iso(thio)cyanates.
Scheme 2: Triflic acid promoted reaction of 2 with ethoxycarbonyl isothiocyanate.
Figure 2: Molecular structure of 4.
Scheme 3: Friedel–Crafts acylation of 2.
Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid
- Anna S. Zalivatskaya,
- Dmitry S. Ryabukhin,
- Marina V. Tarasenko,
- Alexander Yu. Ivanov,
- Irina A. Boyarskaya,
- Elena V. Grinenko,
- Ludmila V. Osetrova,
- Eugeniy R. Kofanov and
- Aleksander V. Vasilyev
Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89
- xylenes, mesitylene, pseudocumene, or durene gave mixtures of oligomeric products. Probably, these products are formed through multiple electrophilic substitution reactions of these arenes by the reactive dication species D. When oxadiazole 1b reacted with tert-butylbenzene (Table 2, entry 10), product 2f
Graphical Abstract
Figure 1: 1,2,4-Oxadiazole-based drugs.
Scheme 1: The hydroarylation of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles 1 under superelectrophilic activat...
Figure 2: General structure for various biologically active compounds containing three carbon atoms, two aryl...
Figure 3: Selected 1H, 13C, 15N NMR data for cations Ca and Cm generated by protonation of oxadiazoles 1a and ...
Figure 4: X-ray crystal structures of compounds 2a (left) (CCDC 1526767) and 2m (right) (CCDC 1526105); ellip...
Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis
- Florin Albota,
- Mino R. Caira,
- Constantin Draghici,
- Florea Dumitrascu and
- Denisa E. Dumitrescu
Beilstein J. Org. Chem. 2016, 12, 2503–2510, doi:10.3762/bjoc.12.245
- interesting chemical reactions of sydnones are their electrophilic substitution at C-4 and their participation in 1,3-dipolar cycloaddition reactions with olefinic and acetylenic dipolarophiles to form pyrazoles and functional transformation at C-4 [20][21][22][23][24][25][26]. Herein we present the synthesis
Graphical Abstract
Figure 1: Sydnone-pyrroloazines hybrids 1, indolizine (2), sydnone 3, indolizines attached directly to C-4 of...
Scheme 1: Synthesis of pyridinium bromides 8 and sydnone-indolizine hybrids 9 through the Chichibabin reactio...
Figure 2: The molecular structure of 9d with thermal ellipsoids drawn at the 50% probability level. (a) Inver...
Figure 3: Centrosymmetric C–H···O hydrogen bonded dimeric motif in the crystal of 9d.
Scheme 2: The synthesis and mechanism of formation of sydnone-indolizines 12.
Figure 4: Molecular structure of 12c with atoms represented as thermal ellipsoids at the 50% probability leve...
Figure 5: Intramolecular distortion in 12c.
A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane
- Donghui Pan,
- Yanbin Wang and
- Guomin Xiao
Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237
- prepare tetrachloroparacyclophane, but a pure polysubstituted product is difficult to obtain by electrophilic substitution without repeated crystallization or chromatographic purification [9]. Thus, we report an improved synthesis method using the Winberg dimerization of 2,5-dichloro-(4-methylbenzyl
Graphical Abstract
Figure 1: Chemical structures of parylene N, parylene C, and parylene D.
Figure 2: Chemical structures of [2.2]paracyclophane and 4,7,12,15-tetrachloro[2.2]paracyclophane.
Scheme 1: Synthesis of substituted (4-methylbenzyl)trimethylammonium bromides from substituted (4-methylbenzy...
Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides
- Ilya V. Efimov,
- Marsel Z. Shafikov,
- Nikolai A. Beliaev,
- Natalia N. Volkova,
- Tetyana V. Beryozkina,
- Wim Dehaen,
- Zhijin Fan,
- Viktoria V. Grishko,
- Gert Lubec,
- Pavel A. Slepukhin and
- Vasiliy A. Bakulev
Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233
- (path 2) reaction mechanisms for the formation of isoxazolines 3a–c as depicted in Scheme 3, in accordance with the proposed reaction mechanisms of heterocyclic enamines proposed earlier by Elliott and co-workers [36]. Path 1 includes the formation of intermediate A as a result of the electrophilic
- substitution of the β-H atom of the enamines 1a,b after treatment with hydroxamoyl chlorides 2a,d,g. The intermediate A undergoes cyclization to oxazolines 3a–c via addition of its hydroxy group onto the double bond of the enamine fragment. This kind of cyclization was ruled out by Elliott et al. [36] because
Graphical Abstract
Figure 1: Biologically active isoxazoles conjugated to other azole rings.
Scheme 1: Reactions of azolyl enamines with nitrile oxides.
Figure 2: Structures of starting enamines 1 and hydroxamoyl chlorides 2.
Scheme 2: Synthesis of 4-azolylisoxazoles 4a–p from enamines 1a–e and hydroxamoyl chlorides 2a–h. Reaction co...
Figure 3: Imidazolylisoxazole 4a according to XRD data in the thermal ellipsoids of the 50% probability level....
Figure 4: Isoxazolylisoxazole 4p according to XRD data with thermal ellipsoids of 50% probability level.
Scheme 3: Plausible mechanisms for reaction of hydroxamoyl chlorides 2 with imidazolyl enamines 1a,b.
Figure 5: Geometries of enamine 1a appropriate to the calculated minima on the PES, and their relative free e...
Scheme 4: Calculated pathways for the formation of experimentally observed 3a, regioisomer 7 and isoxazoline 8...
Figure 6: Structures of the localized transition states. Lengths of the forming bonds are given in Å.
Figure 7: Summary of the calculated pathways of the cycloaddition reaction between enamine 1a and benzonitril...
Figure 8: Isosurface plots of the HOMO of enamine 1a_1 (bottom) and the LUMO of nitrile oxide 6 (top) in the ...
The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors
- Faith M. Akwi and
- Paul Watts
Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186
- is also dependent on the kind of coupling compound used [31]. For example, phenols are successfully coupled in alkaline conditions in which the phenolate ion is formed. These conditions provide the desired electron-releasing group thus facilitating the electrophilic substitution reaction to afford
Graphical Abstract
Scheme 1: PTSA-catalyzed diazotization and azo coupling reaction.
Scheme 2: Ferric hydrogen sulfate (FHS) catalyzed azo compound synthesis.
Scheme 3: Synthesis of azo compounds in the presence of silica supported boron trifluoride.
Scheme 4: Phase transfer catalyzed azo coupling of 5-methylresorcinol in microreactors.
Scheme 5: Synthesis of yellow pigment 12 in a micro-mixer apparatus.
Scheme 6: Continuous flow synthesis of Sudan II azo dye in LTF-MS microreactors.
Figure 1: pH profile plot at constant flow rate of 0.03 mL/min.
Figure 2: pH profile plot at a constant flow rate of 0.7 mL/min.
Scheme 7: Azo coupling reaction under acidic conditions.
Figure 3: pH profile plot at a constant flow rate of 0.03 mL/min.
Figure 4: pH profile plot at constant flow rate of 0.7 mL/min.
Figure 5: Temperature profile plot at constant pH 5.66.
Figure 6: Schematic representation of the microreactor set up.
Figure 7: Schematic representation of the microreactor set up.
Figure 8: Scaled up microreactor set up: PTFE tubing i.d. 1.5 mm a) Chemyx Fusion 100 classic syringe pump, b...
Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands
- Dirk Meyer and
- Thomas Strassner
Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150
- like the bis(1,1'-dimethyl-3,3'-methylenediimidazoline-2,2'-diylidene)palladium(II) dibromide [L2PdBr2] consists of three steps: electrophilic substitution, oxidation and reductive elimination involving a palladium(IV) intermediate [26]. But we also experimentally set out to investigate potential
- should be active according to the proposed catalytic cycle, which starts with an electrophilic substitution reaction. We therefore set out to synthesize the corresponding methyl complexes for the “hybrid ligand” with chloro- and trifluoroacetato ligands. Results and Discussion Synthesis Some time ago we
Graphical Abstract
Scheme 1: Synthesis of the monomethylpalladium(II) complexes 9–11 (in DCM) and 12 (in CH3CN).
Figure 1: Possible isomers.
Figure 2: ORTEP [39] style plot of complex 9 in the solid state. Thermal ellipsoids are given at the 50% probabil...
Figure 3: ORTEP [39] style plot of complex 12 in the solid state. Thermal ellipsoids are drawn at the 50% probabi...
Scheme 2: Synthesis of complex 13.
Figure 4: ORTEP [39] style plot of complex 13 in the solid state. Thermal ellipsoids are drawn at the 50% probabi...
Scheme 3: Possible pathways of methyl trifluoroacetate formation starting from complex 13.
Scheme 4: Synthesis of complex 14 by conversion of complex 13 with iodobenzene bistrifluoroacetate.
Scheme 5: Synthesis of the [((pym)^(NHC-R))PdII(CH3)2] complex 15.
Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides
- Mizuki Yamada,
- Mio Matsumura,
- Yuki Uchida,
- Masatoshi Kawahata,
- Yuki Murata,
- Naoki Kakusawa,
- Kentaro Yamaguchi and
- Shuji Yasuike
Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123
- electrophilic substitution and cross-coupling reaction are in progress. Experimental General procedure for the preparation of compounds 3: CuBr (3.6 mg, 0.025 mmol, 5 mol %), (phenylethynyl)di-p-tolylstibane (1, 203 mg, 0.5 mmol), and an organic azide (2, 0.5 mmol) were dissolved in THF (5 mL). The reaction
Graphical Abstract
Scheme 1: Copper-catalyzed [3 + 2] cycloaddition of 1 with organic azides 2. Reaction conditions: 1 (0.5 mmol...
Figure 1: Ortep drawing of 3a with 50% probability. All hydrogen atoms are omitted for clarity. Two independe...
Scheme 2: Possible mechanism.
Scheme 3: Reaction of 3a with HCl, I2 and NOBF4.
Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies
- Takashi Nishikata,
- Alexander R. Abela,
- Shenlin Huang and
- Bruce H. Lipshutz
Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99
- C–H activation reactions. Palladacycle formation. The generation of cationic Pd(II) from Pd(OAc)2. Electrophilic substitution of aromatic hydrogen by cationic palladium(II) species. Attempted reactions of palladacycle 6. The impact of MeCN on C-H activation/coupling reactions. Stoichiometric MeCN
Graphical Abstract
Figure 1: Road map to enhanced C–H activation reactivity.
Scheme 1: Concerted metalation–deprotonation and elelectrophilic palladation pathways for C–H activation.
Scheme 2: Routes for generation of cationic palladium(II) species.
Scheme 3: Optimized conditions for C–H arylations at room temperature.
Scheme 4: Biaryl formation catalyzed by Pd(OAc)2.
Figure 2: C–H arylation results. Conditions A: Conducted at rt for 20 h in 2 wt % Brij 35/water (1 mL) with 1...
Figure 3: Monoarylations in water at rt. Conditions A: Conducted at rt for 20 h in 2 wt % Brij 35/water with ...
Scheme 5: Selective arylation of a 1-naphthylurea derivative.
Figure 4: Fujiwara–Moritani coupling rreactions in water. Conditions A: 10 mol % [Pd(MeCN)4](BF4)2, 1 equiv B...
Figure 5: Optimization. Conducted at rt for 8 h or as otherwise noted in EtOAc with 10 mol % Pd catalyst, AgO...
Figure 6: Representative results in EtOAc. Conducted at rt in EtOAc with 10 mol % Pd(OAc)2, HBF4 (1 equiv), a...
Scheme 6: Previous syntheses of boscalid®.
Scheme 7: Synthesis of boscalid®. aConducted at rt for 20 h in EtOAc with 10 mol % [Pd(MeCN)4](BF4)2, BQ (5 e...
Scheme 8: Hypothetical reaction sequence for cationic Pd(II)-catalyzed aromatic C–H activation reactions.
Scheme 9: Palladacycle formation.
Figure 7: X-ray structure of palladacycle 6 with thermal ellipsoids at the 50% probability level. BF4 and hyd...
Figure 8: NMR studies. A: The reaction of [Pd(MeCN)4](BF4)2 and 3-MeOC6H4NHCONMe2 in acetone-d6. B: The react...
Scheme 10: The generation of cationic Pd(II) from Pd(OAc)2.
Scheme 11: Electrophilic substitution of aromatic hydrogen by cationic palladium(II) species.
Scheme 12: Attempted reactions of palladacycle 6.
Scheme 13: The impact of MeCN on C-H activation/coupling reactions.
Scheme 14: Stoichiometric MeCN-free reactions. a2% Brij 35 was used instead of EtOAc.
Scheme 15: The reactions of divalent palladacycles.
Scheme 16: Role of BQ in stoichiometric Fujiwara–Moritani and Suzuki–Miyaura coupling reactions. aYields based...
Scheme 17: Proposed role of BQ in Fujiwara–Moritani reactions.
Scheme 18: Proposed role of BQ in Suzuki–Miyaura coupling reactions.
Scheme 19: Stoichiometric C–H arylation of iodobenzene. aYields based on Pd.
Scheme 20: Impact of acetate on the cationicity of Pd.
Scheme 21: Roles of additives in C–H arylation.
Scheme 22: Cross-coupling in the presence of AgBF4.
Scheme 23: A proposed catalytic cycle for Fujiwara–Moritani reactions.
Scheme 24: Proposed catalytic cycle of C–H activation/Suzuki–Miyaura coupling reactions.
Scheme 25: A proposed catalytic cycle for C–H arylation involving a Pd(IV) intermediate.
Scheme 26: Selected reactions of divalent palladacycles.
From steroids to aqueous supramolecular chemistry: an autobiographical career review
- Bruce C. Gibb
Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69
- in useful yields. The highly defined nature of the intermediate lithiate anions is important to the control of these reactions. Thus, much wider ranges of products are observed if direct electrophilic substitution is used as an alternative strategy of host functionalization [24]. As well as proving
Graphical Abstract
Scheme 1: The formation of a 1:1 complex and a 2:1 supramolecular nano-capsule complex from bowl-shaped “cavi...
Scheme 2: Abbreviated synthesis of 7-amino-2-phenyl-6-azaindolizine.
Figure 1: My two favorite compounds for my Ph.D. dissertation, “The Synthesis and Structural Examination of 3...
Scheme 3: An inspiring chlorination from the group of Ronald Breslow.
Scheme 4: The carceplex reaction.
Figure 2: Schematic of a cavitein.
Figure 3: General structure of zinc-TPA complexes.
Scheme 5: Stereoselective bridging of a resorcinarene with benzal halides.
Scheme 6: An eight-fold Ullman ether “weaving” reaction.
Scheme 7: Directed ortho-metallation of the deep-cavity cavitands, showing the mono-endo substituted to tetra-...
Scheme 8: Macrocycle synthesis via resorcinarene covalent templates.
Figure 4: Tris-pyridyl hosts.
Figure 5: (Center) Chemical structure of the octa-acid host. (Left and right) Respective space-filling repres...
Figure 6: Cartoons of the 2:1 host–guest complexes of estradiol (left) and cholesterol (right).
Figure 7: Representative guests for the capsular complexes formed by octa-acid (stoichiometry shown in parent...
Figure 8: A dendrimer-coated cavitand.
Figure 9: Selective oxidation of olefins by singlet oxygen.
Figure 10: a) Preferred packing motifs of methyl, pentyl and octyl guests. b) Product distribution observed fo...
Figure 11: Schematic of the competition of two esters for the capsule formed by octa-acid. The ester that bind...
Figure 12: Schematic of the inter-phase separation of propane and butane; the latter binds more strongly to th...
Figure 13: Structure of tetra-endo-methyl octa-acid (TEMOA).
Figure 14: Assembly properties of TEMOA.
Figure 15: How salts influence the association constant (Ka) for the binding of ClO4– to octa-acid (Figure 4). The ind...
C–H bond halogenation catalyzed or mediated by copper: an overview
- Wenyan Hao and
- Yunyun Liu
Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230
- electrophilic substitution reaction, the occurrence of powerful new synthetic strategies such as transition metal-catalyzed C–H activation brought new opportunities to the synthesis of more diversely halogenated products by enabling the halogenation of more challenging substrates by more selective
Graphical Abstract
Scheme 1: Copper-catalyzed C–H bond halogenation of 2-arylpyridine.
Scheme 2: ortho-Chlorination of 2-arylpridines with acyl chlorides.
Scheme 3: Copper-catalyzed chlorination of 2-arylpyridines using LiCl.
Scheme 4: Copper-catalyzed C–H halogenation of 2-arylpyridines using LiX.
Scheme 5: Copper-mediated selective C–H halogenations of 2-arylpyridine.
Scheme 6: Copper-catalyzed C–H o-halogenation using removable DG.
Scheme 7: Copper-catalyzed C–H halogenations using PIP as DG.
Scheme 8: Copper-catalyzed quinoline C–H chlorination.
Scheme 9: Copper-catalyzed arene C–H fluorination of benzamides.
Scheme 10: Copper-catalyzed arene C–H iodination of 1,3-azoles.
Scheme 11: Copper-catalyzed C–H halogenations of phenols.
Scheme 12: Proposed mechanism for the C–H halogenation of phenols.
Scheme 13: Copper-catalyzed halogenation of electron enriched arenes.
Scheme 14: Copper-catalyzed C–H bromination of arenes.
Scheme 15: CuI-mediated synthesis of iododibenzo[b,d]furans via C–H functionalization.
Scheme 16: Cu-Mn spinel oxide-catalyzed phenol and heteroarene halogenation.
Scheme 17: Copper-catalyzed halogenations of 2-amino-1,3thiazoles.
Scheme 18: Copper-mediated chlorination and bromination of indolizines.
Scheme 19: Copper-catalyzed three-component synthesis of bromoindolizines.
Scheme 20: Copper-mediated C–H halogenation of azacalix[1]arene[3]pyridines.
Scheme 21: Copper-mediated cascade synthesis of halogenated pyrrolones.
Scheme 22: Copper-mediated alkene C–H chlorination in spirothienooxindole.
Scheme 23: Copper-catalyzed remote C–H chlorination of alkyl hydroperoxides.
Scheme 24: Copper-catalyzed C–H fluorination of alkanes.
Scheme 25: Copper-catalyzed or mediated C–H halogenations of active C(sp3)-bonds.
Selected synthetic strategies to cyclophanes
- Sambasivarao Kotha,
- Mukesh E. Shirbhate and
- Gopalkrushna T. Waghule
Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142
- chain elongation of the bis-azulene derivative 76 with a four-carbon unit has been accomplished by electrophilic substitution with 4,4'-dimethoxybutan-2-one (77) under acidic conditions and subsequent elimination of methanol under basic conditions gave the advanced precursor 78 (28%). The
Graphical Abstract
Figure 1: General representation of cyclophanes.
Figure 2: cyclophanes one or more with heteroatom.
Figure 3: Metathesis catalysts 12–17 and C–C coupling catalyst 18.
Figure 4: Natural products containing the cyclophane skeleton.
Figure 5: Turriane family of natural products.
Scheme 1: Synthesis of [3]ferrocenophanes through Mannich reaction. Reagents and conditions: (i) excess HNMe2...
Scheme 2: Synthesis of cyclophanes through Michael addition. Reagents and conditions: (i) xylylene dibromide,...
Scheme 3: Synthesis of normuscopyridine analogue 37 through an oxymercuration–oxidation strategy. Reagents an...
Scheme 4: Synthesis of tribenzocyclotriyne 39 through Castro–Stephens coupling reaction. Reagents and conditi...
Scheme 5: Synthesis of cyclophane 43 through Glaser–Eglinton coupling. Reagents and conditions: (i) 9,10-bis(...
Scheme 6: Synthesis of the macrocyclic C-glycosyl cyclophane through Glaser coupling. Reagents and conditions...
Scheme 7: Synthesis of cyclophane-containing complex 49 through Glaser–Eglinton coupling reaction. Reagents a...
Scheme 8: Synthesis of cyclophane 53 through Glaser–Eglinton coupling. Reagents and conditions: (i) K2CO3, ac...
Figure 6: Cyclophanes 54–56 that have been synthesized through Glaser–Eglinton coupling.
Figure 7: Synthesis of tetrasubstituted [2.2]paracyclophane 57 and chiral cyclophyne 58 through Eglinton coup...
Scheme 9: Synthesis of cyclophane through Glaser–Hay coupling reaction. Reagents and conditions: (i) CuCl2 (1...
Scheme 10: Synthesis of seco-C/D ring analogs of ergot alkaloids through intramolecular Heck reaction. Reagent...
Scheme 11: Synthesis of muscopyridine 73 via Kumada coupling. Reagents and conditions: (i) 72, THF, ether, 20 ...
Scheme 12: Synthesis of the cyclophane 79 via McMurry coupling. Reagents and conditions: (i) 75, decaline, ref...
Scheme 13: Synthesis of stilbenophane 81 via McMurry coupling. Reagents and conditions: (i) TiCl4, Zn, pyridin...
Scheme 14: Synthesis of stilbenophane 85 via McMurry coupling. Reagents and conditions: (i) NBS (2 equiv), ben...
Figure 8: List of cyclophanes prepared via McMurry coupling reaction as a key step.
Scheme 15: Synthesis of paracyclophane by cross coupling involving Pd(0) catalyst. Reagents and conditions: (i...
Scheme 16: Synthesis of the cyclophane 112 via the pinacol coupling and 113 by RCM. Reagents and conditions: (...
Scheme 17: Synthesis of cyclophane derivatives 122a–c via Sonogoshira coupling. Reagents and conditions: (i) C...
Scheme 18: Synthesis of cyclophane 130 via Suzuki–Miyaura reaction as a key step. Reagents and conditions: (i)...
Scheme 19: Synthesis of the mycocyclosin via Suzuki–Miyaura cross coupling. Reagents and conditions: (i) benzy...
Scheme 20: Synthesis of cyclophanes via Wurtz coupling reaction Reagents and conditions: (i) PhLi, Et2O, C6H6,...
Scheme 21: Synthesis of non-natural glycophanes using alkyne metathesis. Reagents and conditions: (i) G-I (12)...
Figure 9: Synthesis of cyclophanes via ring-closing alkyne metathesis.
Scheme 22: Synthesis of crownophanes by cross-enyne metathesis. Reagents and conditions: (i) G-II (13), 5 mol ...
Scheme 23: Synthesis of (−)-cylindrocyclophanes A (156) and (−)-cylindrocyclophanes F (155). Reagents and cond...
Scheme 24: Synthesis of cyclophane 159 derivatives via SM cross-coupling and RCM. Reagents and conditions: (i)...
Scheme 25: Sexithiophene synthesis via cross metathesis. Reagents and conditions: (i) 161, Pd(PPh3)4, K2CO3, T...
Scheme 26: Synthesis of pyrrole-based cyclophane using enyne metathesis. Reagents and conditions: (i) Se, chlo...
Scheme 27: Synthesis of macrocyclic derivatives by RCM. Reagents and conditions: (i) G-I/G-II, CH2Cl2, 0.005 M...
Scheme 28: Synthesis of enantiopure β-lactam-based dienyl bis(dihydrofuran) 179. Reagents and conditions: (i) ...
Scheme 29: Synthesis of a [1.1.6]metaparacyclophane derivative 183 via SM cross coupling. Reagents and conditi...
Scheme 30: Synthesis of a [1.1.6]metaparacyclophane derivative 190 via SM cross coupling. Reagents and conditi...
Scheme 31: Template-promoted synthesis of cyclophanes involving RCM. Reagents and conditions: (i) acenaphthene...
Scheme 32: Synthesis of [3.4]cyclophane derivatives 200 via SM cross coupling and RCM. Reagents and conditions...
Figure 10: Examples for cyclophanes synthesized by RCM.
Scheme 33: Synthesis of the longithorone C framework assisted by fluorinated auxiliaries. Reagents and conditi...
Scheme 34: Synthesis of the longithorone framework via RCM. Reagents and conditions: (i) 213, NaH, THF, rt, 10...
Scheme 35: Synthesis of floresolide B via RCM as a key step. Reagents and conditions: (i) G-II (13, 0.1 equiv)...
Scheme 36: Synthesis of normuscopyridine (223) by the RCM strategy. Reagents and condition: (i) Mg, THF, hexen...
Scheme 37: Synthesis of muscopyridine (73) via RCM. Reagents and conditions: (i) 225, NaH, THF, 0 °C to rt, 1....
Scheme 38: Synthesis of muscopyridine (73) via RCM strategy. Reagents and conditions: (i) NaH, n-BuLi, 5-bromo...
Scheme 39: Synthesis of pyridinophane derivatives 223 and 245. Reagents and conditions: (i) PhSO2Na, TBAB, CH3...
Scheme 40: Synthesis of metacyclophane derivatives 251 and 253. Reagents and conditions: (i) 240, NaH, THF, rt...
Scheme 41: Synthesis of normuscopyridine and its higher analogues. Reagents and conditions: (i) alkenyl bromid...
Scheme 42: Synthesis of fluorinated ferrocenophane 263 via a [2 + 2] cycloaddition. Reagents and conditions: (...
Scheme 43: Synthesis of [2.n]metacyclophanes 270 via a [2 + 2] cycloaddition. Reagents and conditions: (i) Ac2...
Scheme 44: Synthesis of metacyclophane 273 by a [2 + 2 + 2] co-trimerization. Reagents and conditions: (i) [Rh...
Scheme 45: Synthesis of paracyclophane 276 via a [2 + 2 + 2] cycloaddition reaction. Reagents and conditions: ...
Scheme 46: Synthesis of cyclophane 278 via a [2 + 2 + 2] cycloaddition reaction. Reagents and conditions: (i) ...
Scheme 47: Synthesis of cyclophane 280 via a [2 + 2 + 2] cycloaddition. Reagents and conditions: (i) [(Rh(cod)(...
Scheme 48: Synthesis of taxane framework by a [2 + 2 + 2] cycloaddition. Reagents and conditions: (i) Cp(CO)2 ...
Scheme 49: Synthesis of cyclophane 284 and 285 via a [2 + 2 + 2] cycloaddition reaction. Reagents and conditio...
Scheme 50: Synthesis of pyridinophanes 293a,b and 294a,b via a [2 + 2 + 2] cycloaddition. Reagents and conditi...
Scheme 51: Synthesis of pyridinophanes 296 and 297 via a [2 + 2 + 2] cycloaddition. Reagents and conditions: (...
Scheme 52: Synthesis of triazolophane by a 1,3-dipolar cycloaddition. Reagents and conditions: (i) propargyl b...
Scheme 53: Synthesis of glycotriazolophane 309 by a click reaction. Reagents and conditions: (i) LiOH, H2O, Me...
Figure 11: Cyclophanes 310 and 311 prepared via click chemistry.
Scheme 54: Synthesis of cyclophane via the Dötz benzannulation. Reagents and conditions: (i) THF, 100 °C, 12 h...
Scheme 55: Synthesis of [6,6]metacyclophane by a Dötz benzannulation. Reagents and conditions: (i) THF, 100 °C...
Scheme 56: Synthesis of cyclophanes by a Dötz benzannulation. Reagents and conditions: (i) THF, 65 °C, 3 h; (i...
Scheme 57: Synthesis of muscopyridine (73) via an intramolecular DA reaction of ketene. Reagents and condition...
Scheme 58: Synthesis of bis[10]paracyclophane 336 via Diels–Alder reaction. Reagents and conditions: (i) DMAD,...
Scheme 59: Synthesis of [8]paracyclophane via DA reaction. Reagents and conditions: (i) maleic anhydride, 3–5 ...
Scheme 60: Biomimetic synthesis of (−)-longithorone A. Reagents and conditions: (i) Me2AlCl, CH2Cl2, −20 °C, 7...
Scheme 61: Synthesis of sporolide B (349) via a [4 + 2] cycloaddition reaction. Reagents and conditions: (i) P...
Scheme 62: Synthesis of the framework of (+)-cavicularin (352) via a [4 + 2] cycloaddition. Reagents and condi...
Scheme 63: Synthesis of oxazole-containing cyclophane 354 via Beckmann rearrangement. Reagents and conditions:...
Scheme 64: Synthesis of cyclophanes 360a–c via benzidine rearrangement. Reagents and conditions: (i) 356a–d, K2...
Scheme 65: Synthesis of cyclophanes 365a–c via benzidine rearrangement. Reagents and conditions: (i) BocNHNH2,...
Scheme 66: Synthesis of metacyclophane 367 via Ciamician–Dennstedt rearrangement. Reagents and conditions: (i)...
Scheme 67: Synthesis of cyclophane by tandem Claisen rearrangement and RCM as key steps. Reagents and conditio...
Scheme 68: Synthesis of cyclophane derivative 380. Reagents and conditions: (i) K2CO3, CH3CN, allyl bromide, r...
Scheme 69: Synthesis of metacyclophane via Cope rearrangement. Reagents and conditions: (i) MeOH, NaBH4, rt, 1...
Scheme 70: Synthesis of cyclopropanophane via Favorskii rearrangement. Reagents and conditions: (i) Br2, CH2Cl2...
Scheme 71: Cyclophane 389 synthesis via photo-Fries rearrangement. Reagents and conditions: (i) DMAP, EDCl/CHCl...
Scheme 72: Synthesis of normuscopyridine (223) via Schmidt rearrangement. Reagents and conditions: (i) ethyl s...
Scheme 73: Synthesis of crownophanes by tandem Claisen rearrangement. Reagents and conditions: (i) diamine, Et3...
Scheme 74: Attempted synthesis of cyclophanes via tandem Claisen rearrangement and RCM. Reagents and condition...
Scheme 75: Synthesis of muscopyridine via alkylation with 2,6-dimethylpyridine anion. Reagents and conditions:...
Scheme 76: Synthesis of cyclophane via Friedel–Craft acylation. Reagents and conditions: (i) CS2, AlCl3, 7 d, ...
Scheme 77: Pyridinophane 418 synthesis via Friedel–Craft acylation. Reagents and conditions: (i) 416, AlCl3, CH...
Scheme 78: Cyclophane synthesis involving the Kotha–Schölkopf reagent 421. Reagents and conditions: (i) NBS, A...
Scheme 79: Cyclophane synthesis involving the Kotha–Schölkopf reagent 421. Reagents and conditions: (i) BEMP, ...
Scheme 80: Cyclophane synthesis by coupling with TosMIC. Reagents and conditions: (i) (a) ClCH2OCH3, TiCl4, CS2...
Scheme 81: Synthesis of diaza[32]cyclophanes and triaza[33]cyclophanes. Reagents and conditions: (i) DMF, NaH,...
Scheme 82: Synthesis of cyclophane 439 via acyloin condensation. Reagents and conditions: (i) Na, xylene, 75%;...
Scheme 83: Synthesis of multibridged binuclear cyclophane 442 by aldol condensation. Reagents and conditions: ...
Scheme 84: Synthesis of various macrolactones. Reagents and conditions: (i) iPr2EtN, DMF, 77–83%; (ii) TBDMSCl...
Scheme 85: Synthesis of muscone and muscopyridine via Yamaguchi esterification. Reagents and conditions: (i) 4...
Scheme 86: Synthesis of [5]metacyclophane via a double elimination reaction. Reagents and conditions: (i) LiBr...
Figure 12: Cyclophanes 466–472 synthesized via Hofmann elimination.
Scheme 87: Synthesis of cryptophane via Baylis–Hillman reaction. Reagents and conditions: (i) methyl acrylate,...
Scheme 88: Synthesis of cyclophane 479 via double Chichibabin reaction. Reagents and conditions: (i) excess 478...
Scheme 89: Synthesis of cyclophane 483 via double Chichibabin reaction. Reagents and conditions: (i) 481, OH−;...
Scheme 90: Synthesis of cyclopeptide via an intramolecular SNAr reaction. Reagents and conditions: (i) TBAF, T...
Scheme 91: Synthesis of muscopyridine (73) via C-zip ring enlargement reaction. Reagents and conditions: (i) H...
Figure 13: Mechanism of the formation of compound 494.
Scheme 92: Synthesis of indolophanetetraynes 501a,b using the Nicholas reaction as a key step. Reagents and co...
Scheme 93: Synthesis of cyclophane via radical cyclization. Reagents and conditions: (i) cyclododecanone, phen...
Scheme 94: Synthesis of (−)-cylindrocyclophanes A (156) and (−)-cylindrocyclophanes F (155). Reagents and cond...
Scheme 95: Cyclophane synthesis via Wittig reaction. Reagents and conditions: (i) LiOEt (2.1 equiv), THF, −78 ...
Figure 14: Representative examples of cyclophanes synthesized via Wittig reaction.
Scheme 96: Synthesis of the [6]paracyclophane via isomerization of Dewar benzene. Reagents and conditions: (i)...
Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light “on water”
- Julio Benites,
- Juan Meléndez,
- Cynthia Estela,
- David Ríos,
- Luis Espinoza,
- Iván Brito and
- Jaime A. Valderrama
Beilstein J. Org. Chem. 2014, 10, 2448–2452, doi:10.3762/bjoc.10.255
- (1) with phenylamines using oxidants such as K3Fe(CN)6, HIO3 and NaIO4 in aqueous alcohol. According to these authors, the oxidative phenylamination mechanism involves a radical cation intermediate generated by an electron transfer process from the phenylamine to the oxidant. Further electrophilic
- substitution at the 4-position of compound 1 followed by oxidation of the aminonaphthol intermediate, yield the N-phenyl-1,4-naphthoquinone-4-imines. A mechanism involving radical cation intermediates is supported by the rather high product yields resulting from the reaction of 1,5-DHN (1) with electron-donor
Graphical Abstract
Figure 1: Structures of compounds 1–3.
Scheme 1: Hypothetical one-pot synthesis of compound 4a and/or 4b.
Figure 2: Structure of compound 6 determined by single crystal X-ray diffractometry.
Scheme 2: Evaluation of the substrate scope using RB as oxygen (1O2) sensitizer “on water”.
Scheme 3: Evaluation of the oxidative coupling in the absence of RB, on water.
Nonanebis(peroxoic acid): a stable peracid for oxidative bromination of aminoanthracene-9,10-dione
- Vilas Venunath Patil and
- Ganapati Subray Shankarling
Beilstein J. Org. Chem. 2014, 10, 921–928, doi:10.3762/bjoc.10.90
- -9,10-dione, which is highly deactivated towards the electrophilic substitution is investigated. The peracid, nonanebis(peroxoic acid), possesses advantages such as better stability at room temperature, it is easy to prepare and non-shock sensitiv as compared to the conventional peracids. The present
- aminoanthracene-9,10-dione deactivate the ring towards electrophilic substitution [11]. Generally, the bromination of aminoanthracene-9,10-dione is carried out in sulfuric acid [12][13][14][15] (20 to 98%) and nitrobenzene [16][17] at a high temperature (80 to 120 °C) with or without a catalyst (like Cu or CuSO4
- was surmised that in the presence of oxidant these substrates form a diimine type product (similar to oxidative hair dye mechanism) [33], which makes the ring unreactive towards electrophilic substitution. Since Oxone and 50% hydrogen peroxide showed good results with substrate 1a, we have checked the
Graphical Abstract
Scheme 1: Aliphatic peracid mediated bromination of aminoanthracene-9,10-dinone.
Scheme 2: Plausible mechanism for the bromination of aminoanthracene-9,10-dione [36,37].
Continuous flow nitration in miniaturized devices
- Amol A. Kulkarni
Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38
- reactions are fast and highly exothermic. Typically, the nitration of aromatic compounds is acid-catalyzed and it involves an electrophilic substitution where the nitronium ion (NO2+) acts as the reactive species [4][5][6]. Based on estimations of 2007 and the proposed world production capacity, the overall
Graphical Abstract
Figure 1: Analysis of the literature on aromatic nitration over the last 50 years. Numbers next to each nitra...
Figure 2: Schematic of a typical experimental setup for aromatic nitration. The circular segment shown inside...
Scheme 1: Nitration of substituted pyrazole-5-carboxylic acid 1. T = 90 °C, residence time = 35 min, yield: 7...
Scheme 2: Nitration of 2-methylindole (4). T = 3 °C, residence time = 48 s, yield: 70%. [27].
Scheme 3: Nitration of pyridine-N-oxide (6), T = 120 °C, residence time = 80 min, yield: 78% (72% in the flas...
Scheme 4: Nitration of toluene (8). Method 1: H2SO4/HNO3, T = 65 °C, residence time = 15 min. Method 2: Ac2O/H...
Figure 3: Graphical presentation of a microreactor used for double nitration and the schematic of the experim...
Scheme 5: Nitration of 2-amino-6-chloro-4-pyrimidinol (14) [25].
Scheme 6: Nitration of benzaldehyde (16) [35].
Scheme 7: Nitration of salicylic acid (19) [30].
Scheme 8: Nitration of phenol (22) yielding mono-nitro isomers 23 and 24 as main products, hydroquinone (25),...
Scheme 9: Synthesis of 3-methyl-4-nitropyrazole (29) and 3,5-dimethyl-4-nitropyrazole (31) [31].
Figure 4: Photograph of the experimental setup for the synthesis of alkyl-nitropyrazoles. IMM’s SIMM-V2 micro...
Scheme 10: Nitration of chlorobenzene (33) [23].
Figure 5: Continuous flow nitration of chlorobenzene (33) with nitric acid in a sequence of continuously stir...
Scheme 11: Nitration of 2-isopropoxybenzaldehyde (36) by using red fuming nitric acid [37].
Figure 6: Silicon-glass microreactor by Knapkiewicz et al. [37]. (A) Layout of the microreactor with a built-in m...
Scheme 12: Synthesis of nitropyridine (40) [39].
Figure 7: Schematic of the experimental setup involving a pressure based charging system [39]. Reproduced with pe...
Scheme 13: Nitration of p-difluorobenzene (42) [40].
Figure 8: Schematic of the flow reactor arrangement. Reproduced with permission from [40]. Copyright 2013 The Ame...
Scheme 14: Nitration of naphthalene (47) [34].
Figure 9: Structure of the microreactor. (A) Top view (1, 2 – inlets, 3 – mixing points, 4 – outlet). (B) Lat...
Scheme 15: Nitration of 2-nitropropane (52) [38].
Figure 10: Schematic of the continuous nitration system reported in CN103044261A [56].
Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives
- Pablo Morán-Poladura,
- Eduardo Rubio and
- José M. González
Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249
- electron-rich and neutral donor IPr ligand favors the latter cyclization against the former. On this ground, a change in the tethering element switching the linker from NTs to oxygen (Scheme 4A, X = O) results in more activated rings towards aromatic electrophilic substitution processes. To this respect
- moment. In this case, a demanding electrophilic substitution must occur and should produce very efficiently the 3-aurated-4-iodo-2H-chromene C and one equivalent of acid. Next, gold-assisted protonation at C-4 should afford D [57], an intermediate featuring a gold-carbene at C-3, that would require a
Graphical Abstract
Scheme 1: Synthesis of 3-halo-2H-chromenes.
Figure 1: X-ray molecular structure of 2f.
Scheme 2: Gram-scale synthesis of 2f.
Scheme 3: Retaining propargylic chirality.
Scheme 4: Mechanistic basis postulated for the synthesis of 2.
Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes
- Satyajit Haldar and
- Subratanath Koner
Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6
- is known to have a high number of acidic sites in its porous structure [43]. They showed that among various readily available porous aluminosilicates like HSZ-360-Y, ZSM-5-Y, K10 montmorillonite, etc., HSZ-360-Y was capable of catalyzing the electrophilic substitution process. However, a rigorous
