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Search for "monosubstitution" in Full Text gives 26 result(s) in Beilstein Journal of Organic Chemistry.
Photoswitches beyond azobenzene: a beginner’s guide
- Michela Marcon,
- Christoph Haag and
- Burkhard König
Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143
- methods for N-arylation depending on the aryl type: electron-rich and electron-neutral substituents are introduced via Chan–Lam coupling with an arylboronic acid, electron-poor aromatics via Cu(I)-catalysed cross-coupling with aryliodonium salts, and monosubstitution is achieved via Ullman–Goldberg
Graphical Abstract
Figure 1: Energy diagram of a two-state photoswitch. Figure 1 was redrawn from [2].
Figure 2: Example of the absorption spectra of the isomers of a photoswitch with most efficient irradiation w...
Scheme 1: Photoswitch classes described in this review.
Figure 3: Azoheteroarenes.
Scheme 2: E–Z Isomerisation (top) and mechanisms of thermal Z–E isomerisation (bottom).
Scheme 3: Rotation mechanism favoured by the electron displacement in push–pull systems. Selected examples of...
Figure 4: A) T-shaped and twisted Z-isomers determine the thermal stability and the Z–E-PSS (selected example...
Figure 5: Effect of di-ortho-substitution on thermal half-life and PSS.
Figure 6: Selected thermal lifetimes of azoindoles in different solvents and concentrations. aConcentration o...
Figure 7: Aryliminopyrazoles: N-pyrazoles (top) and N-phenyl (bottom).
Scheme 4: Synthesis of symmetrical heteroarenes through oxidation (A), reduction (B), and the Bayer–Mills rea...
Scheme 5: Synthesis of diazonium salt (A); different strategies of azo-coupling: with a nucleophilic ring (B)...
Scheme 6: Synthesis of arylazothiazoles 25 (A) and heteroaryltriazoles 28 (B).
Scheme 7: Synthesis of heteroarylimines 31a,b [36-38].
Figure 8: Push–pull non-ionic azo dye developed by Velasco and co-workers [45].
Scheme 8: Azopyridine reported by Herges and co-workers [46].
Scheme 9: Photoinduced phase transitioning azobispyrazoles [47].
Figure 9: Diazocines.
Scheme 10: Isomers, conformers and enantiomers of diazocine.
Scheme 11: Partial overlap of the ππ* band with electron-donating substituents and effect on the PSS. Scheme 11 was ada...
Figure 10: Main properties of diazocines with different bridges. aMeasured in n-hexane [56]. bMeasured in THF. cMe...
Scheme 12: Synthesis of symmetric diazocines.
Scheme 13: Synthesis of asymmetric diazocines.
Scheme 14: Synthesis of O- and S-heterodiazocines.
Scheme 15: Synthesis of N-heterodiazocines.
Scheme 16: Puromycin diazocine photoswitch [60].
Figure 11: Indigoids.
Figure 12: The main representatives of the indigoid photoswitch class.
Scheme 17: Deactivation process that prevents Z-isomerisation of indigo.
Figure 13: Stable Z-indigo derivative synthesised by Wyman and Zenhäusern [67].
Figure 14: Selected examples of indigos with aliphatic and aromatic substituents [68]. Dashed box: proposed π–π in...
Scheme 18: Resonance structures of indigo and thioindigo involving the phenyl ring.
Scheme 19: Possible deactivation mechanism for 4,4'-dihydroxythioindigo [76].
Scheme 20: Effect of different heteroaryl rings on the stability and the photophysical properties of hemiindig...
Figure 15: Thermal half-lives of red-shifted hemithioindigos in toluene [79]. aMeasured in toluene-d8.
Scheme 21: Structures of pyrrole [81] and imidazole hemithioindigo [64].
Figure 16: Examples of fully substituted double bond hemithioindigo (left), oxidised hemithioindigos (centre),...
Scheme 22: Structure of iminothioindoxyl 72 (top) and acylated phenyliminoindolinone photoswitch 73 (bottom). ...
Scheme 23: (top) Transition states of iminothioindoxyl 72. The planar transition state is associated with a lo...
Scheme 24: Baeyer–Drewsen synthesis of indigo (top) and N-functionalisation strategies (bottom).
Scheme 25: Synthesis of hemiindigo.
Scheme 26: Synthesis of hemithioindigo and iminothioindoxyl.
Scheme 27: Synthesis of double-bond-substituted hemithioindigos.
Scheme 28: Synthesis of phenyliminoindolinone.
Scheme 29: Hemithioindigo molecular motor [85].
Figure 17: Arylhydrazones.
Scheme 30: Switching of arylhydrazones. Note: The definitions of stator and rotor are arbitrary.
Scheme 31: Photo- and acidochromism of pyridine-based phenylhydrazones.
Scheme 32: A) E–Z thermal inversion of a thermally stable push–pull hydrazone [109]. B) Rotation mechanism favoured...
Scheme 33: Effect of planarisation on the half-life.
Scheme 34: The longest thermally stable hydrazone switches reported so far (left). Modulation of thermal half-...
Figure 18: Dependency of t1/2 on concentration and hypothesised aggregation-induced isomerisation.
Figure 19: Structure–property relationship of acylhydrazones.
Scheme 35: Synthesis of arylhydrazones.
Scheme 36: Synthesis of acylhydrazones.
Scheme 37: Photoswitchable fluorophore by Aprahamian et al. [115].
Scheme 38: The four-state photoswitch synthesised by the Cigáň group [116].
Figure 20: Diarylethenes.
Scheme 39: Isomerisation and oxidation pathway of E-stilbene to phenanthrene.
Scheme 40: Strategies adapted to avoid E–Z isomerisation and oxidation.
Scheme 41: Molecular orbitals and mechanism of electrocyclisation for a 6π system.
Figure 21: Aromatic stabilisation energy correlated with the thermal stability of the diarylethenes [127,129].
Figure 22: Half-lives of diarylethenes with increasing electron-withdrawing groups [128,129].
Scheme 42: Photochemical degradation pathway promoted by electron-donating groups [130].
Figure 23: The diarylethenes studied by Hanazawa et al. [134]. Increased rigidity leads to bathochromic shift.
Scheme 43: The dithienylethene synthesised by Nakatani's group [135].
Scheme 44: Synthesis of perfluoroalkylated diarylethenes.
Scheme 45: Synthesis of 139 and 142 via McMurry coupling.
Scheme 46: Synthesis of symmetrical derivatives 145 via Suzuki–Miyaura coupling.
Scheme 47: Synthesis of acyclic 148, malonic anhydride 149, and maleimide derivatives 154.
Figure 24: Gramicidin S (top left) and two of the modified diarylethene derivatives: first generation (bottom ...
Scheme 48: Pyridoxal 5'-phosphate and its reaction with an amino acid (top). The analogous dithienylethene der...
Figure 25: Fulgides.
Scheme 49: The three isomers of fulgides.
Scheme 50: Thermal and photochemical side products of unsubstituted fulgide [150].
Figure 26: Maximum absorption λc of the closed isomer compared with the nature of the aromatic ring and the su...
Scheme 51: Possible rearrangement of the excited state of 5-dimethylaminoindolylfulgide [153].
Figure 27: Quantum yields of ring closure (ΦE→C) and E–Z isomerisation (ΦE→Z) correlated with the increasing s...
Scheme 52: Active (Eα) and inactive (Eβ) conformers (left) and the bicyclic sterically blocked fulgide 169 (ri...
Scheme 53: Quantum yield of ring-opening (ΦC→E) and E–Z isomerisation (ΦE→Z) for different substitution patter...
Scheme 54: Stobbe condensation pathway for the synthesis of fulgides 179, fulgimides 181 and fulgenates 178.
Scheme 55: Alternative synthesis of fulgides through Pd-catalysed carbonylation.
Scheme 56: Optimised synthesis of fulgimides [166].
Scheme 57: Photoswitchable FRET with a fulgimide photoswitch [167].
Scheme 58: Three-state fulgimide strategy by Slanina's group.
Figure 28: Spiropyrans.
Scheme 59: Photochemical (left) and thermal (right) ring-opening mechanisms for an exemplary spiropyran with a...
Figure 29: Eight possible isomers of the open merocyanine according to the E/Z configurations of the bonds hig...
Scheme 60: pH-Controlled photoisomerisation between the closed spiropyran 191-SP and the open E-merocyanine 19...
Scheme 61: Behaviour of spiropyran in water buffer according to Andréasson and co-workers [180]. 192-SP in an aqueo...
Scheme 62: (left box) Proposed mechanism of basic hydrolysis of MC [184]. (right box) Introduction of electron-dona...
Scheme 63: Photochemical interconversion of naphthopyran 194 (top) and spirooxazine 195 (bottom) photoswitches...
Scheme 64: Synthesis of spiropyrans and spirooxazines 198 and the dicondensation by-product 199.
Scheme 65: Alternative synthesis of spiropyrans and spirooxazines with indolenylium salt 200.
Scheme 66: Synthesis of 4’-substituted spiropyrans 203 by condensation of an acylated methylene indoline 201 w...
Scheme 67: Synthesis of spironaphthopyrans 210 by acid-catalysed condensation of naphthols and diarylpropargyl...
Scheme 68: Photoswitchable surface wettability [194].
Figure 30: Some guiding principles for the choice of the most suitable photoswitch. Note that this guide is ve...
A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions
- Vitor A. S. Almodovar and
- Augusto C. Tomé
Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169
- (disubstitution) and non-symmetrical (monosubstitution) DPP derivatives are formed in excellent overall yields. The optical properties of the newly synthesized compounds are also discussed. The new platform may be useful for bioorthogonal chemistry. Keywords: diketopyrrolopyrrole; fluorescent dye; nucleophilic
- functionalized DPP derivatives. As anticipated, it displayed reactivity with thiols and phenols through nucleophilic aromatic substitution at the pentafluorobenzyl groups, yielding both symmetrical (disubstitution) and non-symmetrical (monosubstitution) derivatives in satisfactory yields (Scheme 1). Thiols are
Graphical Abstract
Scheme 1: Synthesis of new diketopyrrolopyrroles via nucleophilic aromatic substitution.
Figure 1: (A) Absorption and (B) fluorescence spectra of compounds 3a–f, 4a, 4d and 4f, in DMF. Different con...
Photoredox catalysis harvesting multiple photon or electrochemical energies
- Mattia Lepori,
- Simon Schmid and
- Joshua P. Barham
Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81
Graphical Abstract
Figure 1: Oxidative and reductive activations of organic compounds harvesting photoredox catalysis.
Figure 2: General catalytic cycles of radical ion conPET (left) and radical ion e-PRC (right).
Figure 3: “Beginner’s guide”: comparison between advantages, capacities, and prospectives of conPET and PEC.
Figure 4: A) conPET reductive dehalogenation of aryl halides with PDI. B) Reductive C–H arylation with pyrrol...
Figure 5: A) Chromoselective mono- and disubstitution or polybrominated pyrimidines with pyrroles. B) Sequent...
Figure 6: A) Synthesis of pyrrolo[1,2-a]quinolines. B) Synthesis of ullazines.
Figure 7: A) Reductive phosphorylation of aryl halides via conPET. B) Selected examples from the substrate sc...
Figure 8: A) Reductive dehalogenation of aryl halides via conPET and selected examples from the substrate sco...
Figure 9: A) Reductive C–H arylation of aryl halides via conPET (top) and selected examples from the substrat...
Figure 10: A) Reductive hydrodehalogenation of aryl halides with Mes-Acr-BF4. B) Selected examples from the su...
Figure 11: A) Reductive hydrodechlorination of aryl chlorides with 4-DPAIPN. B) Proposed formation of CO2•−. C...
Figure 12: A) Reductive conPET borylation with 3CzEPAIPN (top) and selected examples from the substrate scope ...
Figure 13: Scale-up of conPET phosphorylation with 3CzEPAIPN.
Figure 14: A) Borylation of 1d. B) Characteristics and structure of PC1 with green and red parts showing the l...
Figure 15: A) Reductive C–H arylation scope with polysulfide conPET (top) and selected examples from the subst...
Figure 16: Scale-up of A) C–H arylation and B) dehaloborylation with polysulfide photocatalysis in continuous-...
Figure 17: A) Formation of [Ir1]0 and [Ir2]0 upon PET between [Ir1]+ and Et3N. B) Mechanism of multi-photon ta...
Figure 18: A) Reductive hydrodehalogenation of aryl halides via multi-photon tandem photocatalysis. B) Selecte...
Figure 19: A) Carbonylative amidation of aryl halides in continuous flow. B) Selected examples from the substr...
Figure 20: A) General scheme for reductive (RQ) and oxidative quenching (OQ) protocols using [FeIII(btz)3](PF6)...
Figure 21: A) Carbonylative amidation of alkyl iodides with [IrIII(ppy)2(dtbbpy)]PF6. B) Selected examples fro...
Figure 22: A) Carboxylative C–N bond cleavage in cyclic amines. B) Selected examples from the substrate scope....
Figure 23: A) Formal reduction of alkenes to alkanes via transfer hydrogenation. B) Selected examples from the...
Figure 24: A) Birch-type reduction of benzenes with PMP-BPI. B) Selected examples from the substrate scope (sc...
Figure 25: Proposed mechanism of the OH− mediated conPET Birch-type reduction of benzene via generation of sol...
Figure 26: Reductive detosylation of N-tosylated amides with Mes-Acr-BF4. B) Selected examples from the substr...
Figure 27: A) Reductive detosylation of N-tosyl amides by dual PRC. B) Selected examples from the substrate sc...
Figure 28: A) Mechanism of the dual PRC based on PET between [Cu(dap)2]+ and DCA. B) Mechanism of the dual PRC...
Figure 29: A) N–O bond cleavage in Weinreb amides with anthracene. B) N–O bond cleavage in Weinreb amides rely...
Figure 30: A) Pentafluorosulfanylation and fluoride elimination. B) Mechanism of the pentafluorosulfanylation ...
Figure 31: A) α-Alkoxypentafluorosulfanylation (top) and selected examples from the substrate scope (bottom). ...
Figure 32: A) Oxidative amination of arenes with azoles catalyzed by N-Ph PTZ. B) Selected examples from the s...
Figure 33: A) C(sp3)–H bond activation by HAT via chloride oxidation by *N-Ph PTZ•+. B) Proposed mechanism for...
Figure 34: A) Recycling e-PRC C–H azolation of electron-rich arenes with pyrazoles using Mes-Acr+ as a photoca...
Figure 35: A) Radical ion e-PRC direct oxidation of unactivated arenes using TAC+ as an electro-activated phot...
Figure 36: A) Radical ion e-PRC direct oxidation of unactivated arenes using TPA as an electro-activated photo...
Figure 37: Proposed mechanism (top) and mode of preassembly (bottom).
Figure 38: A) Possible preassemblies of reactive (left) vs unreactive (right) arenes. B) Calculated spin densi...
Figure 39: A) Recycling e-PRC C(sp2 )–H acetoxylation of arenes using DDQ as a photocatalyst. B) Proposed cata...
Figure 40: Gram scale hydroxylation of benzene in a recirculated flow setup.
Figure 41: A) Radical ion e-PRC vicinal diamination of alkylarenes using TAC+ as an electro-activated photocat...
Figure 42: A) Sequential oxygenation of multiple adjacent C–H bonds under radical ion e-PRC using TAC+ as an e...
Figure 43: A) Enantioselective recycling e-PRC cyanation of benzylic C–H bonds using ADQS as photocatalyst. B)...
Figure 44: Proposed tandem mechanism by Xu and co-workers.
Figure 45: A) Enantioselective recycling e-PRC decarboxylative cyanation using Cu(acac)2, Ce(OTf)3 and a box l...
Figure 46: A) Enantioselective recycling e-PRC benzylic cyanation using Cu(MeCN)4BF4, box ligand and anthraqui...
Figure 47: A) Radical ion e-PRC acetoxyhydroxylation of aryl olefins using TAC+ as an electro-activated photoc...
Figure 48: Selected examples from the substrate scope.
Figure 49: Photoelectrochemical acetoxyhydroxylation in a recirculated flow setup.
Figure 50: A) Radical ion e-PRC aminooxygenation of aryl olefins using TAC+ as an electro-activated photocatal...
Figure 51: A) Recycling e-PRC C–H alkylation of heteroarenes with organic trifluoroborates using Mes-Acr+ as p...
Figure 52: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using CeCl3·7H2O as catalyst. B) ...
Figure 53: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using Fe(NH4)2(SO4)2·6H2O as cata...
Figure 54: A) Recycling e-PRC C–H alkylation of heteroarenes with alkyl oxalates and 4CzIPN as photocatalyst. ...
Figure 55: A) Recycling e-PRC decarboxylative C–H carbamoylation of heteroarenes using 4CzIPN as photocatalyst...
Figure 56: A) Photoelectrochemical HAT-mediated hydrocarbon activation via the chlorine radical. B) Proposed m...
Figure 57: A) Selected examples from the substrate scope. B) Gram and decagram scale semi-continuous flow PEC ...
Figure 58: A) Photoelectrochemical HAT-mediated dehydrogenative coupling of benzothiazoles with aliphatic C–H ...
Figure 59: A) Photoelectrochemical HAT activation of ethers using electro-activated TAC+ as photocatalyst. B) ...
Figure 60: Selected examples from the substrate scope.
Figure 61: A) Photoelectrochemical HAT-mediated synthesis of alkylated benzimidazo-fused isoquinolinones using...
Figure 62: A) Decoupled photoelectrochemical cerium-catalyzed oxydichlorination of alkynes using CeCl3 as cata...
Figure 63: Proposed decoupled photoelectrochemical mechanism.
Figure 64: A) Decoupled photoelectrochemical ring-opening bromination of tertiary cycloalkanols using MgBr2 as...
Figure 65: A) Recycling e-PRC ring-opening functionalization of cycloalkanols using CeCl3 as catalyst. B) Prop...
Figure 66: Selected examples from the substrate scope of the PEC ring-opening functionalization.
Figure 67: A) Radical ion e-PRC reduction of chloro- and bromoarenes using DCA as catalyst and various accepto...
Figure 68: A) Screening of different phthalimide derivatives as catalyst for the e-PRC reduction of aryl halid...
Figure 69: Screening of different organic catalysts for the e-PRC reduction of trialkylanilium salts.
Figure 70: A) e-PRC reduction of phosphonated phenols and anilinium salts. B) Selected examples from the subst...
Figure 71: A) ConPET and e-PRC reduction of 4-bromobenzonitrile using a naphthalene diimide (NDI) precatalyst ...
Figure 72: A) Radical ion e-PRC reduction of phosphinated aliphatic alcohols with n-BuO-NpMI as catalyst. B) C...
Figure 73: Selected examples from the substrate scope.
Figure 74: A) Recycling e-PRC reductive dimerization of benzylic chlorides using a [Cu2] catalyst. B) Proposed...
Figure 75: A) Decoupled photoelectrochemical C–H alkylation of heteroarenes through deamination of Katritzky s...
Figure 76: Proposed mechanism by Chen and co-workers.
Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin
- János Máté Orosz,
- Dóra Ujj,
- Petr Kasal,
- Gábor Benkovics and
- Erika Bálint
Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25
- ; monosubstitution; reduction; Introduction Cyclodextrins (CDs), as cyclic oligosaccharides, consist of a macrocyclic ring of glucose subunits linked by α-1,4-glycosidic bonds [1]. They are widely used in pharmaceutical, food and chemical industries, as well as in agriculture. It has been known for decades, that CD
- the CD molecule where the monofunctionalization can occur. Consequently, monosubstituted CDs can be mixtures of three regioisomers. The number of known monosubstituted CD derivatives is enormous, since monosubstitution was the almost exclusive reaction for the practical production of selectively
- easier process than the optimization of a new monosubstitution reaction on a native CD [5]. Monotosylation of the primary rim of CDs is the most widely used method to obtain C-6 monofunctionalized CDs. Tosyl chloride (TsCl) reacts with α-, β-, and γ-CD in pyridine to give the C-6-monosubstituted product
Graphical Abstract
Scheme 1: Tosylation of β-CD under continuous flow conditions.
Scheme 2: Continuous flow azidation of Ts-β-CD (2).
Scheme 3: Continuous flow hydrogenation of N3-β-CD (3).
Scheme 4: Semi-continuous flow system for the synthesis of NH2-β-CD 4.
Combining the best of both worlds: radical-based divergent total synthesis
- Kyriaki Gennaiou,
- Antonios Kelesidis,
- Maria Kourgiantaki and
- Alexandros L. Zografos
Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1
- quenchers (e.g., PhSSPh) to the reaction mixture. When monosubstitution of the aryl group is present, the formed radical cation, the product of the photooxidation of the cinnamyl ether, readily cyclizes to cyclobutene radical cation 217. The latter cleaves the benzylic C–C bond to produce the 1,4-radical
- nucleophile is employed, radical 223 is favored, leading to either monosubstitution or disubstitution with external nucleophiles, depending on the presence of oxidant or reductant in the reaction mixture. Based on this plan, Zhu’s group managed to synthesize a rich number of lignans and congeners, such as
Graphical Abstract
Scheme 1: The power of radical retrosynthesis and the tactic of divergent total synthesis.
Figure 1: Evolution of radical chemistry for organic synthesis.
Scheme 2: Divergent total synthesis of α-pyrone-diterpenoids (Baran).
Scheme 3: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part I, ...
Scheme 4: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part II,...
Scheme 5: Divergent synthesis of drimane-type hydroquinone meroterpenoids (Li).
Scheme 6: Divergent synthesis of natural products isolated from Dysidea avara (Lu).
Scheme 7: Divergent synthesis of kaurene-type terpenoids (Lei).
Scheme 8: Divergent synthesis of 6-oxabicyclo[3.2.1]octane meroterpenoids (Lou).
Scheme 9: Divergent synthesis of crinipellins by radical-mediated Dowd–Backwith rearrangement (Xie and Ding).
Scheme 10: Divergent total synthesis of Galbulimima alkaloids (Shenvi).
Scheme 11: Divergent synthesis of eburnane alkaloids (Qin).
Scheme 12: Divergent synthesis of Aspidosperma alkaloids (Boger).
Scheme 13: Photoredox based synthesis of (−)-FR901483 (160) and (+)-TAN1251C (162, Gaunt).
Scheme 14: Divergent synthesis of bipolamines (Maimone).
Scheme 15: Flow chemistry divergency between aporphine and morphinandione alkaloids (Felpin).
Scheme 16: Divergent synthesis of pyrroloazocine natural products (Echavarren).
Scheme 17: Using TEMPO to stabilize radicals for the divergent synthesis of pyrroloindoline natural products (...
Scheme 18: Radical pathway for preparation of lignans (Zhu).
Scheme 19: Divergent synthesis of DBCOD lignans (Lumb).
Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides
- Shengli Zuo,
- Shuxiang Zheng,
- Jianjun Liu and
- Ang Zuo
Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147
- -aryloxy alcohols were thereafter synthesized through the KR of epichlorohydrin with different phenols using chiral Co–salen catalyst 2f (Table 3). meta-Substituted methylphenol showed less reactivity and selectivity (Table 3, entry 2), while tert-butyl monosubstitution at the para-position on the phenol
Graphical Abstract
Figure 1: Representative asymmetric Co–salen catalysts.
Scheme 1: Synthetic approach to our unsymmetrical Co–salen catalyst 2f for the asymmetric synthesis of α-aryl...
Scheme 2: Mechanochemical one-pot two-step synthesis of unsymmetrical salens 1a–h. Reaction conditions: salic...
Scheme 3: Synthesis of unsymmetrical metal–salen complexes 2. Reaction conditions a: metal acetate hydrate (1...
New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions
- Iveta Chena Tichá,
- Simona Hybelbauerová and
- Jindřich Jindřich
Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80
- modification of native CD skeletons with new functional groups enhances the application of CDs and provides access to new organic chemistry transformations and catalytic systems. Among the approaches used for chemical derivatization of CD skeletons, monosubstitution on the primary rim of CD (Figure 1) is a
Graphical Abstract
Figure 1: Schematic cone-shaped (a) and structure representations (b) of α-CD (six glucopyranoside units) and...
Figure 2: Common cinchona alkaloids (cinchonine, cinchonidine, quinine, quinidine).
Scheme 1: CuAAC click reaction of propargylated cinchona alkaloids 3a–d with 6I-azido-6I-deoxy-α-CD (1) and 6I...
Scheme 2: CuAAC click reaction of per-Me-N3-α-CD (6) or per-Me-N3-β-CD (7) and propargylated cinchona alkaloi...
Scheme 3: Synthesis of difunctionalized α-CD 11 with quinine moieties.
Figure 3: Representative 1H NMR spectrum of the non-methylated quinidine–α-CD derivative 4d.
Figure 4: Representative 13C NMR spectrum and parts of the HMBC spectrum of the non-methylated quinidine–α-CD...
Scheme 4: AAA reaction of MBH carbamate 12 catalyzed by the prepared CD derivatives 4a–d, 5a–d, 8a–d, 9a–d, 11...
Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry
- Gábor Benkovics,
- Mihály Bálint,
- Éva Fenyvesi,
- Erzsébet Varga,
- Szabolcs Béni,
- Konstantina Yannakopoulou and
- Milo Malanga
Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66
- high selectivity towards the primary rim in monosubstitution of β-CD [22][23]. Our assumption was that targeting the disubstituted product with the same tosylating agent would preserve the side-selectivity and significantly reduce the number of possible regioisomers (6A,6B-, 6A,6C- and 6A,6D-ditosyl-β
Graphical Abstract
Figure 1: Schematic representation of β-CD with glucopyranose atom numbering and with alphabetic labeling of ...
Scheme 1: Syntheses of 6A,6X-diazido-β-CDs as reference compounds using the “capping” literature method [11,12].
Scheme 2: Syntheses of homo-difunctionalized β-CDs using different reaction conditions.
Figure 2: HPLC chromatograms of the authentic 6A,6X-diazido-β-CDs with known regiochemistry (references 1–3, Scheme 1...
Figure 3: NMR spectral regions of the three ditosyl regioisomers in D2O (500 MHz). The signals of the tosylat...
Scheme 3: Syntheses of 6A-monoazido-6X-monotosyl-β-CDs using starting materials obtained from different react...
Figure 4: Reversed-phase HPLC chromatograms of 6A-monoazido-6X-monotosyl-β-CDs prepared through reactions 4–8....
Figure 5: HPLC separation of regioisomers and pseudoenantiomers of 6A-monoazido-6X-monotosyl-β-CD prepared in...
Figure 6: Reversed-phase HPLC chromatograms of 6A,6X-diazido-β-CDs prepared in reactions 9–13.
Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands
- Tegene T. Tole,
- Johan H. L. Jordaan and
- Hermanus C. M. Vosloo
Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19
- temperatures. The high stability, very good activity, selectivity, TON and TOF of the four precatalysts, at high temperatures, proved that the hemilability of the bidentate hemilabile pyridinyl alcoholato ligand can be influenced by monosubstitution on the pyridinyl moiety. A Ru/1-octene precatalyst
Graphical Abstract
Figure 1: Structures of Grubbs 1 (1) and 2 (2) precatalysts.
Scheme 1: Design concepts for ruthenium alkylidene precatalysts [3].
Figure 2: Structures of Grubbs 1-type (3) and 2-type (4) pyridinyl-alcoholato precatalysts.
Figure 3: Structures of Grubbs 2-type (5) pyridinyl-alcoholato precatalysts.
Figure 4: Structures of pyridinyl-substituted Grubbs 2-type pyridinyl-alcoholato precatalysts.
Figure 5: The influence of the reaction temperature on the (a) conversion of 1-octene, (b) formation of PMPs ...
Figure 6: The influence of the reaction temperature on the (a) conversion of 1-octene, (b) formation of PMPs ...
Figure 7: The influence of the reaction temperature on the (a) conversion of 1-octene, (b) formation of PMPs ...
Figure 8: The influence of the reaction temperature on the (a) conversion of 1-octene, (b) formation of PMPs ...
Figure 9: Geometry-optimised structures of precatalyst 9, 6 and 8.
Figure 10: An illustration of the envisaged methoxy oxygen lone pair-aromatic π-electron interaction.
Figure 11: Influence of precatalysts 6–9 and 5d on the (a) conversion of 1-octene and (b) ln([n%1-octene]) ver...
Figure 12: 1H NMR spectra of the carbene-Hα region at different time intervals of the 1-octene/7 reaction mixt...
Figure 13: 1H NMR spectra of the Hα region of the pyridine ring of the 1-octene/7 reaction mixture in toluene-d...
Scheme 2: Synthesis of pyridinyl-alcohol ligands and Grubbs 2-type pyridinyl-alcoholato complexes.
Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives
- Iveta Tichá,
- Gábor Benkovics,
- Milo Malanga and
- Jindřich Jindřich
Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261
- , among other fields [2]. Recent studies have improved the properties of CD scaffolds primarily by selective persubstitution and monosubstitution [2][3], thereby broadening their application. However, the synthesis of selectively disubstituted CD derivatives with the same or different functional groups at
Graphical Abstract
Figure 1: Schematic representation of native α-CD (1) and top view of its primary rim with alphabetic clockwi...
Scheme 1: Synthesis of 6A,6X-diazido-α-CD derivatives 4 via 6A,6X-capped α-CDs 2 and 3 and their regioisomeri...
Scheme 2: Synthesis of 6A,6X- and 6A,6D-diazido-α-CDs via 6A,6X-dibromo-α-CD 5, 6A,6D-dibromo-α-CD 5d interme...
Scheme 3: Synthesis of 6A,6X-diazido-α-CDs via 6A,6X-ditosyl-α-CD intermediates 6 and their regioisomeric rat...
Figure 2: HPLC chromatograms of 6A,6X-diazido-α-CDs 4 of the reactions 1–5, with ACN/water gradient elution a...
Scheme 4: Synthesis of 6A-azido-6X-mesitylenesulfonyl-α-CD 8 and conversion into 6A,6X-diazido-α-CD 4.
Figure 3: HPLC chromatograms of reaction 7 with separated 6A-azido-α-CD 7 as starting material and regioisome...
Figure 4: HPLC chromatograms of 6A-azido-6X-mesitylenesulfonyl-α-CD 8 (reaction 6): a) analytical and b) prep...
Figure 5: 1H NMR spectrum of the AC regioisomer 8c as a mixture of pseudoenantiomers prepared through reactio...
Figure 6: 13C NMR spectrum of the AC regioisomer 8c as a mixture of pseudoenantiomers prepared through reacti...
Figure 7: HPLC–MS chromatogram with the separated pseudoenantiomers of 6A-azido-6B-mesitylenesulfonyl-α-CD 8b...
Synthesis of dihydroquinazolines from 2-aminobenzylamine: N3-aryl derivatives with electron-withdrawing groups
- Nadia Gruber,
- Jimena E. Díaz and
- Liliana R. Orelli
Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227
- -ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration
Graphical Abstract
Figure 1: N-Aryl-3,4-dihydroquinazolines 1.
Scheme 1: Synthetic pathway leading to N-aryl-3,4-dihydroquinazolines 1.
Scheme 2: Synthesis of compounds 2.
Figure 2: Reaction intermediate in the synthesis of compound 2a.
Scheme 3: Addition–elimination mechanism for the heterocyclization.
Scheme 4: Proposed mechanism involving an intermediate nitrilium ion.
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
- -TsOH in aqueous acetonitrile at 75 °C for 4 h afforded the benzotropolone 241. 5.3.2. Reaction of 7-hydroxy-2,3-benzotropone (241): Various monosubstitution products 289–291 of 7-hydroxy-2,3-benzotropone (241) were readily prepared by Nozoe’s group (Figure 12) [174]. The synthesis of bromo-derivative
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.
Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure
- Denisa Vargová,
- Rastislav Baran and
- Radovan Šebesta
Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42
- (see Supporting Information File 1 for more details) [37][38][39][40]. The amine 9 was then attached to a squaramide moiety using dimethyl squarate (10) in slight excess to ensure monosubstitution. In this way compound 11 was isolated in 80% yield. We have originally envisaged the transformation from
Graphical Abstract
Figure 1: Structures of pregabalin and methylpregabalin.
Scheme 1: Synthesis of the nitroalkene 6.
Scheme 2: Catalyst screening in the Michael addition of dimethyl malonate to nitroalkene 6.
Scheme 3: Synthesis of catalysts (Sa,R,R)-C8 and (Sa,S,S)-C8.
Figure 2: Transition state models for the reaction of (R)-6 with dimethyl malonate using catalyst C7 (M06-2X/...
Scheme 4: Synthesis of 4-methylpregabalin (1).
Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin
- Markéta Bláhová,
- Sergey K. Filippov,
- Lubomír Kováčik,
- Jiří Horský,
- Simona Hybelbauerová,
- Zdenka Syrová,
- Tomáš Křížek and
- Jindřich Jindřich
Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248
- group at position 2 is the most acidic, and the group at position 3 is most sterically hindered. Therefore, regioselective monosubstitution to positions 2 and 6 can be controlled by the amount and strength of the base used in the reaction, whereas monosubstitution at position 3 can be achieved by
Graphical Abstract
Scheme 1: Preparation of 2I-O-, 3I-O- and 6I-O-naphthylallyl derivatives of γ-CD by cross-metathesis.
Scheme 2: Preparation of 2-O-, 3-O- and 6-O-NA derivatives of γ-CD by direct alkylation (see Table 1 for the yields ...
Figure 1: Volume-weighted distribution functions for water solutions of 2-O- (2a), 3-O- (2b), and 6-O- (2c) N...
Figure 2: Distribution functions for 2-O- (2a), 3-O- (2b), and 6-O- (2c) NA-γ-CD regioisomers in 50% MeOH (v/...
Figure 3: Volume-weighted distribution functions for the 3-O- (2b) and 6-O- (2c) NA-γ-CD regioisomer at diffe...
Figure 4: Effect of increasing concentration and sonication on the morphology of the 3-O-derivative 2b. A to ...
Figure 5: Effect of increasing concentration and sonication on the morphology of the 2-O-derivative 2a. A: 2 ...
Figure 6: Effect of increasing concentration and sonication on the morphology of the 6-O-derivative 2c. A: 0....
Figure 7: Heat change for injection per mole of NA-γ-CD added as a function of the total concentration of NA-...
Figure 8: 1H NMR spectra of 2-O-derivative 2a in D2O at concentrations of 100, 10, and 1 mM.
Figure 9: 1H NMR spectra of 3-O-derivative 2b in D2O at concentrations of 100, 10, and 1 mM.
Figure 10: Putative objects and interactions in naphthylallyl-γ-CD solution, depicted schematically for 6I-O-n...
Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds
- M. Fernanda N. N. Carvalho,
- Rudolf Herrmann and
- Gabriele Wagner
Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122
- formed propargyl group is isomerized to an allene moiety, obviously due to the excess of the strongly basic lithium salt [35]. This unexpected monosubstitution remains unexplained and is not applicable as basis for a general selective synthesis of monoalkynylcamphor derivatives. Alkynes can also be
Graphical Abstract
Scheme 1: Synthesis of 3-oxo-camphorsulfonylimine (3) [13,15] and its bis-alkynyl derivatives 4 from camphor-10-sulf...
Scheme 2: Reactions of bis-alkynyl camphor derivative 4a with TiCl4 and with Br2, respectively.
Scheme 3: Reactions of bis-alkynylcamphor derivatives 4a–e with catalytic amounts of PtCl2(PhCN)2.
Scheme 4: Attempted selective synthesis of 3-alkynyl derivatives via sulfonylimine reduction of oxoimide 3.
Scheme 5: Selective synthesis of 2-alkynyl derivatives by protection of the 3-oxo group as an acetal.
Scheme 6: Selective synthesis of 2-alkynyl derivatives by protection of the 3-oxo group as an imine.
Scheme 7: Synthesis of the bis-alkynyl derivatives bearing different alkyne substituents and their platinum-c...
Scheme 8: Proposed mechanism of the platinum-catalysed cycloisomerisation.
Novel β-cyclodextrin–eosin conjugates
- Gábor Benkovics,
- Damien Afonso,
- András Darcsi,
- Szabolcs Béni,
- Sabrina Conoci,
- Éva Fenyvesi,
- Lajos Szente,
- Milo Malanga and
- Salvatore Sortino
Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52
- protons unambiguously confirms the monosubstitution pattern (DS = 1) in both cases and was further proven by electrospray ionization mass spectrometry (ESIMS) analysis of the compounds (see Supporting Information File 1). The signals in the aromatic region are well resolved (see Figures S25 and S33
Graphical Abstract
Figure 1: Reaction scheme for the synthesis of eosin Y (2) and eosin B (4).
Figure 2: Reaction scheme for the synthesis of eosin-appended β-CDs, 2–β-CD and 4–β-CD (NMM: N-methylmorpholi...
Figure 3: TLC analysis of the composition of the crude coupling reaction mixtures.
Figure 4: 1H NMR spectrum of 2–β-CD with partial assignment (DMSO-d6, 600 MHz, 298 K).
Figure 5: Size distributions of 1 mM aqueous solutions of conjugates 4–β-CD (a) and 2–β-CD (b) at 25.0 °C (pH...
Figure 6: Normalized absorption spectra of aqueous solutions of (a) eosin Y (2) and (b) conjugate 2–β-CD and ...
Figure 7: Time-resolved fluorescence observed for aqueous solutions of (a) eosin Y (2) and (b) the 2–β-CD con...
Figure 8: 1O2 luminescence detected upon 528 nm light excitation of D2O solutions of (a) eosin Y (2) and (b) 2...
Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins
- Laszlo Jicsinszky,
- Marina Caporaso,
- Katia Martina,
- Emanuela Calcio Gaudino and
- Giancarlo Cravotto
Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230
- exchange required considerably larger halogen/reagent ratios than the solution reactions, sulfur nucleophiles showed a more favourable tendency and the reagent/halogen ratio was either roughly equal or slightly lower than for the monosubstitution. In the solution synthesis [6] of β-CD-per-6-dodecane
- yields that were usually lower that those given by the monosubstitution reactions [22]. The very low aqueous solubility of the CD halides led to the intact starting materials being completely lost during the work-up. The low TU/halogen ratio (entries 2, 7 and 8 in Table 1) gave incomplete reactions
Graphical Abstract
Scheme 1: Synthesis of per-6-derivatized CDs. Ball milling conditions: 1500 steel balls of 1 mm diameter and ...
Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques
- Gabor Benkovics,
- Ondrej Hodek,
- Martina Havlikova,
- Zuzana Bosakova,
- Pavel Coufal,
- Milo Malanga,
- Eva Fenyvesi,
- Andras Darcsi,
- Szabolcs Beni and
- Jindrich Jindrich
Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11
- compound is unsubstituted at the C6 position, since the characteristic peaks of the two magnetically non-equivalent proton (C6-Ha and C6-Hb), typical for C6 substitution [12] are not detectable in the spectrum. As a consequence the compound is C2- or C3-monosubstituted (the monosubstitution has also been
Graphical Abstract
Figure 1: Example of elucidation of 2D NMR spectra of 2-O-Cin-α-CD.
Figure 2: 2D ROESY spectrum of 2-O-Cin-α-CD in D2O at 25 °C at 24 mM concentration.
Figure 3: Expansion of the 2D ROESY spectrum of 2-O-Cin-α-CD indicating the geometric arrangement.
Figure 4: 1H NMR spectra of 2-O-Cin-α-CD in D2O at 25 °C at different concentrations.
Figure 5: 1H NMR spectra of 3-O-Cin-α-CD in D2O at 25 °C recorded at various concentrations.
Figure 6: Diffusion coefficients of 2-O-Cin-α-CD (black) and, 3-O-Cin-α-CD (red) in D2O at various concentrat...
Figure 7: Effect of solvent on the size distribution of aggregates formed by 2-O-Cin-α-CD at 25 °C (the appli...
Figure 8: Effect of a solvent on the size distribution of aggregates formed by 3-O-Cin-α-CD at 25 °C (the app...
Figure 9: Aggregate sizes (diameter) of 2-O-Cin-α-CD (black) and 3-O-Cin-α-CD (red) in water at various tempe...
Figure 10: Schematic representation of the DLS experiment proving the host–guest nature of the aggregate forma...
Figure 11: The effect of competitive additives on the size distribution of aggregates formed by 3-O-Cin-α-CD a...
Figure 12: Expansion of the 2D ROESY spectrum of 2-O-Cin-α-CD in the presence of CioOK as competitive guest mo...
Figure 13: 1H NMR spectrum of 2-O-Cin-α-CD before (up) and after (down) the addition of CioOK in 5-fold molar ...
Figure 14: The influence of 5 mM 2-O-Cin-α-CD in BGE (right column) on the decrease of the effective electroph...
Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization
- William H. Hersh
Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19
- of the product was observed, it was not a clean reaction. The N-methylimidazolium triflate (NMI·Tf) method reported for the monosubstitution of diamidites was found to be effective [53], resulting in relatively clean formation of amidites 10 and 11 (Scheme 3). The initial reaction produced a yellow
Graphical Abstract
Figure 1: Acyl phosphorus compounds.
Scheme 1: Synthesis of a dinucleoside acylphosphonate (3b) and a formate diester (1a).
Scheme 2: Reaction of an H-phosphonodiamidite with acid chlorides.
Figure 2: ORTEP [52] drawing of 9. Selected distances (Å) and angles (°): P–N1 1.687(1), P–N2 1.679(1), P–C1 1.87...
Scheme 3: Synthesis of dinucleosides.
Scheme 4: Calculated phosphine, acylphosphine, phosphite, and acylphosphonite inversion barriers.
Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers
- Milo Malanga,
- Mihály Bálint,
- István Puskás,
- Kata Tuza,
- Tamás Sohajda,
- László Jicsinszky,
- Lajos Szente and
- Éva Fenyvesi
Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319
- the case of the β-CD the 60 min reaction was considered to be optimal for the 6-monosubstitution (Figure 1) and the identical conditions were used for the modification of the polymer. In order to set the correct molar ratio between the reagents it is necessary (but not sufficient) to know the Mw of
Graphical Abstract
Scheme 1: Schematic representation of the various synthetic routes for the introduction of an anchoring group...
Scheme 2: Synthetic strategy for the rhodaminylation of β-CD polymer.
Figure 1: TLC study of β-CD iodination showing the proceeding of 6-monoiodination with increasing reaction ti...
Figure 2: HSQC-DEPT spectrum of compound 1 with partial assignment.
Figure 3: IR spectra of compound 1 (black line) and compound 2 (red line) showing the disappearance of the az...
Scheme 3: Schematic representation for the coumarinylation of methylated β-CD-polymer, n, m, p and q mean the...
Figure 4: HSQC-DEPT spectra of compound 4 with partial assignment; in the upper part the full spectrum is sho...
Scheme 4: Schematic representation for the introduction of NBF in a cationic β-CD-polymer.
Scheme 5: Schematic representation for the introduction of fluorescein into a β-CD-polymer.
A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges
- Martin Popr,
- Simona Hybelbauerová and
- Jindřich Jindřich
Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142
- methylation. The majority of the presented reactions are very straightforward with a simple work-up, which avoids the need of chromatographic separation. Thus, these reactions are suitable for the multigram-scale production of monosubstituted cationic CDs. Keywords: cationic; cyclodextrins; monosubstitution
- crystalization from water. So we developed a new chromatography-free method for the purification of the reaction mixture by crystalization. Monosubstitution of β-CD was carried out by the reaction of p-toluenesulfonic anhydride in aqueous NaOH as described previously in literature [17]. The reaction yielded a
Graphical Abstract
Figure 1: Schematic representation of the prepared sets of permanently charged CD derivatives.
Scheme 1: Synthesis of monotrimethylammonio-CD derivatives.
Scheme 2: Preparation of diamines 7 and 8 as reagents for further synthesis [29].
Scheme 3: Synthesis of PEMEDA-CD derivatives.
Scheme 4: Synthesis of PEMPDA-CD derivatives.
Scheme 5: Synthesis of 1-azido-2-iodoethane.
Scheme 6: Synthesis of azidoethane-containing derivatives of PEMEDA and PEMPDA-β-CD.
Scheme 7: Synthesis of CD derivatives monosubstituted with a quaternary triamine moiety.
Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis
- Tao Wang,
- Patrick Rabe,
- Christian A. Citron and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311
- and 1,2,4-trichloro-3-methoxybenzene by monosubstitution [23], but small amounts of disubstitution products were also formed that were rigorously purified from the mixture by repeated column chromatography. Starting from 1,2,3,5-tetrachlorobenzene (12) the same reaction conditions also provided a
Graphical Abstract
Figure 1: Total ion chromatogram of a CLSA headspace extract from Geniculosporium.
Figure 2: Mass spectra of A) the chlorinated volatile X and B) the chlorinated volatile Y.
Figure 3: Constitutional isomers of chlorodimethoxybenzene as candidate structures for X.
Scheme 1: Synthesis of chlorodimethoxybenzenes as reference compounds for X.
Figure 4: Constitutional isomers of dichlorodimethoxybenzene as candidate structures for Y.
Scheme 2: Synthesis of chlorodimethoxybenzenes as reference compounds for Y.
Figure 5: Known natural products that are structurally related to 4b and 10b from Geniculosporium.
Figure 6: Total ion chromatograms of headspace extracts from S. chartreusis. A) Growth on 84 GYM showing prod...
Figure 7: Calicheamicin, a known iodinated compound from the actinomycete Micromonspora echinospora.
New developments in gold-catalyzed manipulation of inactivated alkenes
- Michel Chiarucci and
- Marco Bandini
Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294
- ). Even unsubstituted substrate 31 afforded the corresponding product 32 in excellent yield although more forcing conditions were necessary (Scheme 9c). Monosubstitution at carbon C1 or C2 of the chain led to the formation of the product 2,4-cis or 2,5-cis-32 with diastereomeric ratios up to 5.5:1
Graphical Abstract
Figure 1: Elementary steps in the gold-catalyzed nucleophilic addition to olefins.
Figure 2: Different approaches for the gold-catalyzed manipulation of inactivated alkenes.
Figure 3: Computed mechanistic cycle for the gold-catalyzed alkoxylation of ethylene with PhOH.
Scheme 1: [Au(I)]-catalyzed addition of phenols and carboxylic acids to alkenes.
Scheme 2: [Au(III)] catalyzed annulations of phenols and naphthols with dienes.
Scheme 3: [Au(III)]-catalyzed addition of aliphatic alcohols to alkenes.
Scheme 4: [Au(III)]-catalyzed carboalkoxylation of alkenes with dimethyl acetals 6.
Figure 4: Postulated mechanism for the [Au(I)]-catalyzed hydroamination of olefins.
Scheme 5: Isolation and reactivity of alkyl gold intermediates in the intramolecular hydroamination of alkene...
Scheme 6: [Au(I)]-catalyzed intermolecular hydroamination of dienes.
Scheme 7: Intramolecular [Au(I)]-catalyzed hydroamination of alkenes with carbamates.
Scheme 8: [Au(I)]-catalyzed inter- as well as intramolecular addition of sulfonamides to isolated alkenes.
Scheme 9: Intramolecular hydroamination of N-alkenylureas catalyzed by gold(I) carbene complex.
Scheme 10: Enantioselective hydroamination of alkenyl ureas with biphenyl tropos ligand and chiral silver phos...
Scheme 11: Intramolecular [Au(I)]-catalyzed hydroamination of N-allyl-N’-aryl ureas. (PNP = pNO2-C6H4, PMP = p...
Scheme 12: [Au(I)]-catalyzed hydroamination of alkenes with ammonium salts.
Scheme 13: Enantioselective [Au(I)]-catalyzed intermolecular hydroamination of alkenes with cyclic ureas.
Scheme 14: Mechanistic proposal for the cooperative [Au(I)]/menthol catalysis for the enantioselective intramo...
Scheme 15: [Au(III)]-catalyzed addition of 1,3-diketones to alkenes.
Scheme 16: [Au(I)]-catalyzed intramolecular addition of β-keto amides to alkenes.
Scheme 17: Intermolecular [Au(I)]-catalyzed addition of indoles to alkenes.
Scheme 18: Intermolecular [Au(III)]-catalyzed hydroarylation of alkenes with benzene derivatives and thiophene....
Scheme 19: a) Intramolecular [Au(III)]-catalyzed hydroarylation of alkenes. b) A SEAr-type mechanism was hypot...
Scheme 20: Intramolecular [Au(I)]-catalyzed hydroalkylation of alkenes with simple ketones.
Scheme 21: Proposed reaction mechanism for the intramolecular [Au(I)]-catalyzed hydroalkylation of alkenes wit...
Scheme 22: Tandem Michael addition/hydroalkylation catalyzed by [Au(I)] and [Ag(I)] salts.
Scheme 23: Intramolecular [Au(I)]-catalyzed tandem migration/[2 + 2] cycloaddition of 1,7-enyne benzoates.
Scheme 24: Intramolecular [Au(I)]-catalyzed cyclopropanation of alkenes.
Scheme 25: Stereospecificity in [Au(I)]-catalyzed hydroalkoxylation of allylic alcohols.
Scheme 26: Mechanistic investigation on the intramolecular [Au(I)]-catalyzed hydroalkoxylation of allylic alco...
Scheme 27: Mechanistic investigation on the intramolecular enantioselective [Au(I)]-catalyzed alkylation of in...
Scheme 28: Synthesis of (+)-isoaltholactone via stereospecific intramolecular [Au(I)]-catalyzed alkoxylation o...
Scheme 29: Intramolecular enantioselective dehydrative amination of allylic alcohols catalyzed by chiral [Au(I...
Scheme 30: Enantioselective intramolecular hydroalkylation of allylic alcohols with aldehydes catalyzed by 20c...
Scheme 31: Gold-catalyzed intramolecular diamination of alkenes.
Scheme 32: Gold-catalyzed aminooxygenation and aminoarylation of alkenes.
Scheme 33: Gold-catalyzed carboamination, carboalkoxylation and carbolactonization of terminal alkenes with ar...
Scheme 34: Synthesis of tricyclic indolines via gold-catalyzed formal [3 + 2] cycloaddition.
Scheme 35: Gold(I) catalyzed aminoarylation of terminal alkenes in presence of Selectfluor [dppm = bis(dipheny...
Scheme 36: Mechanistic investigation on the aminoarylation of terminal alkenes by bimetallic gold(I) catalysis...
Scheme 37: Proposed mechanism for the aminoarylation of alkenes via [Au(I)-Au(I)]/[Au(II)-Au(II)] redox cataly...
Scheme 38: Oxyarylation of terminal olefins via redox gold catalysis.
Scheme 39: a) Intramolecular gold-catalyzed oxidative coupling reactions with aryltrimethylsilanes. b) Oxyaryl...
Scheme 40: Oxy- and amino-arylation of alkenes by [Au(I)]/[Au(III)] photoredox catalysis.
Camera-enabled techniques for organic synthesis
- Steven V. Ley,
- Richard J. Ingham,
- Matthew O’Brien and
- Duncan L. Browne
Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118
- vessel, and consequently they employed a borescope camera to visualise the interior of the reactor. This allowed the authors to make phase measurements by visual inspection, to discover that with n-propanol as the alkylating agent, the best results for monosubstitution were obtained by using either
Graphical Abstract
Figure 1: The evolution of computer-based monitoring and control within the laboratory of the future. (a) In ...
Figure 2: A selection of the wide range of digital camera devices available, focusing on those that can be at...
Figure 3: (a) Network cameras (Linksys WVC54GC) in operation in the Innovative Technology Centre laboratory. ...
Figure 4: Remote transmission of video imagery and reaction monitoring data.
Figure 5: A camera can assist the chemist in a number of ways. Digital video recordings of reactions can be u...
Figure 6: Suzuki–Miyaura reaction performed within a microfluidic system. The product is observed by high-spe...
Figure 7: Friedel–Crafts reactions performed by using solid-acid catalysis at high pressures. A camera allowe...
Figure 8: (a) The video camera setup providing a view of the reaction within the microwave cavity; (b) a pall...
Figure 9: (a) Buchwald–Hartwig coupling within a microchannel reactor. (b) Camera view of aggregate deposits ...
Figure 10: The key diprotected piperazic acid precursor in the synthesis of chloptosin.
Figure 11: (a) Piperazic acid mixture, and (b) apparatus for enantiomeric upgrading by recorded crystallisatio...
Figure 12: (a) Crystallisation of a Mn(II) polyoxometalate. (b) A bespoke reactor produced using additive fabr...
Figure 13: Computer processing of digital imagery produces numerical data for later processing.
Figure 14: (a) The Morphologi G3 particle image analyser, which uses images captured with a camera microscope ...
Figure 15: Use of the Python Imaging Library to analyse the proportion of an image consisting of red pixels. A...
Figure 16: (a) Arduino [73,75], a flexible open-source platform for rapidly prototyping electronic applications. (b) ...
Figure 17: Patented device incorporating a standard 96-well plate illuminated by a white-light source. The pla...
Figure 18: Simple colour-change experiments to assess a new AF-2400 gas permeable flow reactor. The reactor co...
Figure 19: (a) Ozonolysis of a series of alkenes using ozone in a bottle-reactor; (b) Glaser–Hay coupling usin...
Figure 20: (a) Camera-assisted titration of ammonia using bromocresol green. NH3 is dissolved in the gas-flow ...
Figure 21: (a) Bubble-counting setup. As the output of the gas-flow reactor (hydrogen dissolved in dichloromet...
Figure 22: Usage of digital cameras to enable remote control of reactions.
Figure 23: In-line solvent switching apparatus. The reactor output is directed into a bottle positioned on a h...
Figure 24: Catch and Release apparatus. (1) The amide intermediate is sequestered onto the central sulfonic ac...
Figure 25: Clips from video footage showing the silica reagent changing appearance; the arrows indicate the ed...
Figure 26: Combination of computer vision and automation to enable machine-assisted synthetic processes.
Figure 27: A coloured float at the interface between heavy and light solvents allows a camera to recognise the...
Figure 28: Graphical demonstration of the image-recognition process. At the start of the experiment, the colou...
Figure 29: Application of the computer-vision-enabled liquid–liquid extractor. The product mixture of a hydraz...
Figure 30: Application of a computer-vision technique to measure the dispersion of a plug of material passing ...
Figure 31: Multiple extractors in series controlled by a single camera.
Figure 32: Two-step synthesis of branched aldehydes from aryl iodides using two reactive gases. A liquid–liqui...
Structural conditions required for the bridge lithiation and substitution of a basic calix[4]arene
- Conrad Fischer,
- Wilhelm Seichter and
- Edwin Weber
Beilstein J. Org. Chem. 2011, 7, 1602–1608, doi:10.3762/bjoc.7.188
- -bromosuccinimide used, surprisingly only monosubstitution of the chalice is observed by application of the lithiation technique, independent of the amount of n-BuLi. However, twofold substitution on opposite methylene bridges can be achieved by successive application of the latter technique [6]. This may suggest
- potentially accessible for guest inclusion, which is also reflected by a comparatively low packing index (62.9) of the crystal [15]. Conclusion It was shown that the bridge monosubstitution of a basic calix[4]arene via lithiation requires a high conformational flexibility of the calixarene, which is the case
Graphical Abstract
Scheme 1: Calix[4]arene tetraethers 1–4 and corresponding bridge monosubstituted carboxylic acid derivatives 5...
Figure 1: A: Four fundamental conformations of a calix[4]arene. B: Arrangement of the methylene group substit...
Scheme 2: Pathways to the calixarene acids 13 and 14 bearing mixed ether functions in different fashions.
Figure 2: 1H NMR spectrum (CDCl3, 293 K, 500 MHz) of calixarene ether 12 before (A) and after the addition of...
Figure 3: Crystal structure of compound 12. For clarity only one of the two crystallographically independent ...
