Search results
Search for "reaction mechanisms" in Full Text gives 135 result(s) in Beilstein Journal of Organic Chemistry.
Learning from B12 enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis
- Keishiro Tahara,
- Ling Pan,
- Toshikazu Ono and
- Yoshio Hisaeda
Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232
- -enzymatic conditions offers good understanding of their elaborate reaction mechanisms. Furthermore, bio-inspiration offers a new approach to catalytic design for green and eco-friendly molecular transformations. As part of a study based on vitamin B12 derivatives including heptamethyl cobyrinate perchlorate
Graphical Abstract
Figure 1: (a) Structure and (b) reactivity of B12.
Figure 2: (a) Schematic representation of B12 enzyme-involving systems. (b) Construction of biomimetic and bi...
Scheme 1: (a) Carbon-skeleton rearrangement mediated by a coenzyme B12-depenedent enzyme. (b) Electrochemical...
Scheme 2: Electrochemical carbon-skeleton arrangements mediated by B12 model complexes.
Figure 3: Key electrochemical reactivity of 1 and 2 in methylated forms.
Scheme 3: Carbon-skeleton arrangements mediated by B12-vesicle artificial enzymes.
Scheme 4: Carbon-skeleton arrangements mediated by B12-HSA artificial enzymes.
Scheme 5: Photochemical carbon-skeleton arrangements mediated by B12-Ru@MOF.
Scheme 6: (a) Methyl transfer reaction mediated by B12-dependent methionine synthase. (b) Methyl transfer rea...
Scheme 7: Methyl transfer reaction for the detoxification of inorganic arsenics.
Scheme 8: (a) Dechlorination of 1,1,2,2-tetrarchloroethene mediated by a reductive dehalogenase. (b) Electroc...
Scheme 9: Visible-light-driven dechlorination of DDT using 1 in the presence of photosensitizers.
Scheme 10: 1,2-Migration of a phenyl group mediated by the visible-light-driven catalytic system composed of 1...
Scheme 11: Ring-expansion reactions mediated by the B12-TiO2 hybrid catalyst with UV-light irradiation.
Scheme 12: Trifluoromethylation and perfluoroalkylation of aromatic compounds achieved through electrolysis wi...
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
- value of these methods to medicinal chemistry is considered. An overview of the general characteristics of the photocatalysts as well as some electrochemical data is presented. In addition, the general reaction mechanisms for organocatalysed photoredox transformations are discussed and some individual
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.
Functionalization of graphene: does the organic chemistry matter?
- Artur Kasprzak,
- Agnieszka Zuchowska and
- Magdalena Poplawska
Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177
- misunderstandings from the reported covalent functionalization methods are discussed, and a direct link between the reaction mechanisms and the basic principles of organic chemistry is taken into special consideration. Keywords: characterization; functionalization; graphene; modification; synthesis design
- , reaction mechanisms, and state of the art of organic chemistry. Point-by-point recommendations are also given for the proper application of organic chemistry principles in covalent functionalization of graphene-family materials. The chemistry of the reactive groups of graphene-family materials covers many
- stacking. As mentioned above in the discussion of reaction mechanisms, water molecules significantly lower the reaction rates for the desired nucleophiles. Importantly, water molecules also influence the hydrolysis of the activated carboxyl groups (Figure 2, step d and Figure 3, step f). Water should
Graphical Abstract
Figure 1: Partial structure [7,8] of the (a) graphene oxide (GO) and (b) reduced graphene oxide (RGO).
Figure 2: Mechanism of the amidation/esterification-type reactions with the GO/RGO using carbodiimide and N-h...
Figure 3: Mechanism of the Steglich esterification with the GO/RGO: (a) acid–base reaction of the carboxyl gr...
Figure 4: Mechanism of the epoxide ring opening reaction with the GO/RGO.
Figure 5: Generation of the free amine (nucleophile) from the corresponding amine hydrohalide using an acid–b...
Figure 6: Mechanism of amidation/esterification-type reactions with the GO/RGO using 1,1’-carbonyldiimidazole...
Figure 7: Mechanism of the covalent functionalization of graphene-family material applying diazonium salts ch...
Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion
- Eric Detmar,
- Valentin Müller,
- Daniel Zell,
- Lutz Ackermann and
- Martin Breugst
Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130
- intermediates and transition states. Keywords: catalysis; C–H activation; density functional theory; London dispersion; reaction mechanisms; Introduction For a long time, large and bulky substituents have intuitively been considered to act through unfavorable steric interactions, although London dispersion
Graphical Abstract
Scheme 1: Cycloaddition reaction of in situ generated benzynes resulting in the sterically more hindered addu...
Scheme 2: Recently developed cobalt-catalyzed C–H cyanation [30].
Figure 1: Calculated free-energy profile for the cobalt-catalyzed C–H cyanation of 2-phenylpyridine (1a) [in ...
Figure 2: Calculated structures, selected bond lengths (in Å), and imaginary frequencies for representative i...
Scheme 3: Kinetic profile of the cobalt-catalyzed C–H cyanation with differently substituted cyanating agents ...
Figure 3: Noncovalent interaction (NCI) analysis for selected intermediates and transition states. The gradie...
Figure 4: Projected dispersion interaction density (DID) plots for selected intermediates and transition stat...
A survey of chiral hypervalent iodine reagents in asymmetric synthesis
- Soumen Ghosh,
- Suman Pradhan and
- Indranil Chatterjee
Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107
- -oxytosylation of ketones by using a new family of chiral hypervalent iodine catalyst 21 with up to 46% ee [67]. The investigation of the reaction mechanisms revealed that the steric crowding around the iodine center improves the enantioselectivity (Scheme 18). Asymmetric oxygenation and nitrogenation reactions
Graphical Abstract
Scheme 1: An overview of different chiral iodine reagents or precursors thereof.
Scheme 2: Asymmetric oxidation of sulfides by chiral hypervalent iodine reagents.
Scheme 3: Oxidative dearomatization of naphthol derivatives by Kita et al.
Scheme 4: [4 + 2] Diels–Alder dimerization reported by Birman et al.
Scheme 5: m-CPBA guided catalytic oxidative naphthol dearomatization.
Scheme 6: Oxidative dearomatization of phenolic derivatives by Ishihara et al.
Scheme 7: Oxidative spirocyclization applying precatalyst 11 developed by Ciufolini et al.
Scheme 8: Asymmetric hydroxylative dearomatization.
Scheme 9: Enantioselective oxylactonization reported by Fujita et al.
Scheme 10: Dioxytosylation of styrene (47) by Wirth et al.
Scheme 11: Oxyarylation and aminoarylation of alkenes.
Scheme 12: Asymmetric diamination of alkenes.
Scheme 13: Stereoselective oxyamination of alkenes reported by Wirth et al.
Scheme 14: Enantioselective and regioselective aminofluorination by Nevado et al.
Scheme 15: Fluorinated difunctionalization reported by Jacobsen et al.
Scheme 16: Aryl rearrangement reported by Wirth et al.
Scheme 17: α-Arylation of β-ketoesters.
Scheme 18: Asymmetric α-oxytosylation of carbonyls.
Scheme 19: Asymmetric α-oxygenation and α-amination of carbonyls reported by Wirth et al.
Scheme 20: Asymmetric α-functionalization of ketophenols using chiral quaternary ammonium (hypo)iodite salt re...
Scheme 21: Oxidative Intramolecular coupling by Gong et al.
Scheme 22: α-Sulfonyl and α-phosphoryl oxylation of ketones reported by Masson et al.
Scheme 23: α-Fluorination of β-keto esters.
Scheme 24: Alkynylation of β-ketoesters and amides catalyzed by phase-transfer catalyst.
Scheme 25: Alkynylation of β-ketoesters and dearomative alkynylation of phenols.
Stereochemical outcomes of C–F activation reactions of benzyl fluoride
- Neil S. Keddie,
- Pier Alexandre Champagne,
- Justine Desroches,
- Jean-François Paquin and
- David O'Hagan
Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6
- matrix indicated that the dominant isomer was the same as was produced in entry 1, Table 3. Therefore, this analysis showed that the dominant enantiomer of 10 arose from an inversion, rather than retention, of configuration of the original stereocenter of 1. There may be four different reaction
- mechanisms operating in these Friedel–Crafts reactions as shown in Figure 4. (A) Coordination of the fluorine atom with the hydrogen bond donor, followed by backside attack of the nucleophile leads to SN2 reaction and inversion of configuration. (B) Hydrogen bond donor coordination to fluorine leads to
Graphical Abstract
Figure 1: C–F activation of benzylic fluorides to generate benzylamine or diarylmethane products.
Figure 2: 7-[2H1]-(R)-Benzyl fluoride ((R)-1).
Scheme 1: Synthesis of enantioenriched 7-[2H1]-(R)-benzyl fluoride ((R)-1) from benzaldehyde (2).
Figure 3: Partial 2H{1H} NMR (107.5 MHz) with PBLG in CHCl3 (13% w/w). (A) racemic sample of 6 (from Table 1, entry ...
Scheme 2: Synthesis of enantioenriched (S)-diarylmethane 10 from diaryl ketone 11 and confirmation of configu...
Figure 4: Possible reactive intermediates for C–F activation of benzyl fluoride 1 with strong hydrogen bond d...
From dipivaloylketene to tetraoxaadamantanes
- Gert Kollenz and
- Curt Wentrup
Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1
- of the bisdioxines becomes severely hindered in cyclic derivatives, so that the 38-membered ring compound 32 requires microwave heating at 170 °C to form tetraoxaadamantane 33, and the catenated compound 36 and calix[6]arene derivative 37 did not form tetraoxaadamantanes. The reaction mechanisms of
Graphical Abstract
Scheme 1: Synthetic routes to 2,4,6,8-tetraoxaadamantanes.
Scheme 2: Conversion of dipivaloylketene (2) to bisdioxines (2,6,9-trioxabicyclo[3.3.1]nona-3,7-dienes) 4 and...
Scheme 3: 2,6,9-Trioxabicyclo[3.3.1]nonadienes (bisdioxines, 9–13) derived from dipivaloylketene (2).
Scheme 4: Mechanisms of formation of bisdioxine acid derivatives from dimer 3.
Scheme 5: Recently reported synthesis of chromenobisdioxines.
Scheme 6: Formation of tetraoxaadamantanes.
Scheme 7: Decarboxylative hydrolysis and oxa-Michael-type ring closure.
Scheme 8: Oxime and hydrazine derivatives of bisdioxines and tetraoxaadamantanes.
Figure 1: Bistetraoxaadamantane derivatives.
Scheme 9: Inward-pointing isocyanate, urethane and carbamate groups in bisdioxines. The diisocyanate is obtai...
Scheme 10: Microwave-assisted tetraoxaadamantane formation.
Scheme 11: Cyclic bisdioxine ester derivative 34 forming a single mono-tetraoxaadamantane.
Figure 2: Cyclic bisdioxine derivative not forming a tetraoxaadamantane due to reduced cavity size.
Figure 3: The bisdioxine-calix[6]arene derivative 37 complexes Cs+ but does not form a tetraoxaadamantane der...
Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies
- Grzegorz Mlostoń and
- Heinz Heimgartner
Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221
- dicyanofumarates and maleates as highly functionalized electron-deficient dipolarophiles, dienophiles and Michael acceptors is summarized. The importance for the studies on reaction mechanisms of cycloadditions is demonstrated. Multistep reactions with 1,2-diamines and β-aminoalcohols leading to diverse five- and
- [3 + 2]-cycloadditions with dialkyl dicyanofumarates E-1 and maleates Z-1 are important from the point of view of the interpretation of reaction mechanisms of cycloadditions. The results obtained with electron-rich thiocarbonyl S-methanides 16 demonstrate that the classical concerted mechanism
- isomeric homo-Diels–Alder adducts were found in the mixture. [3 + 2]-Cycloadditions (1,3-dipolar cycloadditions) Electron-rich 1,3-dipoles such as thiocarbonyl S-methanides and azomethine ylides react with dipolarophiles E-1 and Z-1 to give five-membered cycloadducts through stepwise zwitterionic reaction
Graphical Abstract
Figure 1: Dialkyl dicyanofumarates E-1 and dicyanomaleates Z-1.
Scheme 1: Methods for the synthesis of dialkyl dicyanofumarates E-1 from alkyl cyanoacetates 2.
Scheme 2: Methods for the synthesis of dialkyl dicyanofumarates E-1 from alkyl bromoacetates 3.
Scheme 3: Reaction of dimethyl dicyanofumarate (E-1b) with dimethoxycarbene [(MeO)2C:] generated in situ from...
Scheme 4: Cyclopropanation of diethyl dicyanofumarate (E-1a) through reaction with the thiophene derived sulf...
Scheme 5: Cyclopropanation of dimethyl dicyanofumarate (E-1b) through a stepwise reaction with the in situ ge...
Scheme 6: The [2 + 2]-cycloadditions of dimethyl dicyanofumarate (E-1b) with electron-rich ethylenes 20 and 22...
Scheme 7: The [2 + 2]-cycloaddition of isomeric dimethyl dicyanofumarate (E-1b) and dicyanomaleate (Z-1b) wit...
Scheme 8: Non-concerted [2 + 2]-cycloaddition between E-1b and bicyclo[2.1.0]pentene (27).
Scheme 9: Stepwise [3 + 2]-cycloadditions of some thiocarbonyl S-methanides with dialkyl dicyanofumarates E-1...
Scheme 10: Stepwise [3 + 2]-cycloadditions of dimethyl dicyanofumarate (E-1b) and dimethyl dicyanomaleate (Z-1b...
Scheme 11: [3 + 2]-Cycloaddition of diazomethane with dimethyl dicyanofumarate (E-1b) leading to 1H-pyrazole d...
Scheme 12: Reversible Diels–Alder reaction of fulvenes 36 with diethyl dicyanofumarate (E-1a).
Scheme 13: [4 + 2]-Cycloaddition of 9,10-dimethylanthracene (39b) and E-1a.
Scheme 14: Stepwise [4 + 2]-cycloaddition of dimethyl dicyanofumarate (E-1b) with electron-rich 1,1-dimethoxy-...
Scheme 15: Formal [4 + 2]-cycloaddition of 3,4-di(α-styryl)furan (47) with dimethyl dicyanofumarate (E-1b).
Scheme 16: Acid-catalyzed Michael addition of enolizable ketones of type 49 to E-1.
Scheme 17: Reaction of diethyl dicyanofumarate (E-1a) with ammonia NH3.
Scheme 18: Reaction of dialkyl dicyanofumarates E-1 with primary and secondary amines.
Scheme 19: Reaction of dialkyl dicyanofumarates E-1 with 1-azabicyclo[1.1.0]butanes 55.
Scheme 20: Formation of pyrazole derivatives in the reaction of hydrazines with E-1.
Scheme 21: Formation of 5-aminopyrazole-3,4-dicarboxylate 65 via heterocyclization reactions.
Scheme 22: Reactions of aryl- and hetarylcarbohydrazides 67 with E-1a.
Scheme 23: Multistep reaction leading to perhydroquinoxaline derivative 73.
Scheme 24: Synthesis of ethyl 7-aminopteridin-6-carboxylates 75 via a domino reaction.
Scheme 25: Synthesis of morhpolin-2-ones 80 from E-1 and β-aminoalcohols 78 through an initial aza-Michael add...
Scheme 26: Reaction of 3-amino-5-arylpyrazoles 81 with dialkyl dicyanofumarates E-1 via competitive nucleophil...
Scheme 27: Heterocyclization reaction of thiosemicarbazone 86 with E-1a.
Scheme 28: Formation of diethyl 4-cyano-5-oxotetrahydro-4H-chromene-3,4-dicarboxylate (90) from E-1a via heter...
Scheme 29: Reaction of dialkyl dicyanofumarates E-1 with cysteamine (92).
Scheme 30: Formation of disulfides through reaction of thiols with E-1a.
Scheme 31: Formation of CT salts of E-1 with Mn2+ and Cr2+ metallocenes through one-electron transfer.
Scheme 32: Oxidation of diethyl dicyanofumarate (E-1a) with H2O2 to give oxirane 101.
Scheme 33: The aziridination of E-1b through nitrene addition.
The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy
- Patrick A. Julien,
- Ivani Malvestiti and
- Tomislav Friščić
Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216
- mechanochemical reactions. A significant recent advance in mechanistic studies of mechanochemical reaction mechanisms was the introduction of techniques for in situ, real-time monitoring of ball milling processes [27], first through synchrotron X-ray powder diffraction (XRPD) [28][29], and later by Raman
Graphical Abstract
Scheme 1: Milling synthesis of 2,3-diphenylquinoxaline from benzil and ortho-phenylenediamine [40].
Scheme 2: Movement of the milling jar and sample holder under milling conditions.
Figure 1: Time-resolved Raman spectrum for the double condensation of o-phenylenediamine and benzil to form 2...
Figure 2: Section of the time-resolved Raman spectrum for the model mechanochemical reaction conducted at 30 ...
Figure 3: (Left) Estimated contribution of each component for each Raman spectrum over time of the synthesis ...
Figure 4: The effect of milling frequency on the milling condensation of benzil and o-phenylenediamine to for...
Figure 5: The reproducibility of varying milling frequency on the neat mechanochemical condensation of benzil...
Figure 6: The effect of milling frequency on the internal jar temperature measured immediately after reaction...
Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes
- José Enrique Barquera-Lozada and
- Gabriel Cuevas
Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192
- energetic evolution of germacranolides’ Cope transformations. Computational methods DFT has been proved to be a good method for the study of reaction mechanisms of natural products' biogenesis and it has been used in many studies [44][45][46][47][48][49][50][51][52][53][54][55] and it is the method of
Graphical Abstract
Scheme 1: Biogenetic hypothesis for the transformation of schkuhriolide (1) into elemanschkuriolide (3).
Figure 1: Reaction paths M (blue), N (orage), O (yellow) and P (green) for the transformation of 1 into 3. Re...
Scheme 2: Similar compounds to melampolide 1 unable to be hemiacetaled.
Figure 2: Schematic representations of the calculated C5 epimeric structures of 2 and 3. Relative electronic ...
Figure 3: Reaction paths of the Cope rearrangements of closed (dark blue and orange) and open (red and pink) ...
A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes
- Grzegorz Mlostoń,
- Paulina Pipiak,
- Róża Hamera-Fałdyga and
- Heinz Heimgartner
Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185
- presented protocol offers a new, highly efficient approach to tetrasubstituted ethenes and dibenzofulvenes bearing aryl and/or hetaryl substituents. Keywords: diazomethanes; 1,3-dipolar cycloadditions; olefination reactions; reaction mechanisms; thioketones; Introduction Aryl and hetaryl-substituted
Graphical Abstract
Scheme 1: Reactions of diphenyl and phenyl selenophen-2-yl thioketones with diazomethane (CH2N2; Sel = seleno...
Scheme 2: Reaction of diaryl thioketones with trimethylsilyldiazomethane (TMS-CHN2).
Scheme 3: Formation of tetraaryl/hetarylethenes 9 from the reaction of TMS-CHN2 with diaryl/hetaryl thioketon...
Scheme 4: Synthesis of dibenzofulvenes 9g–k.
Scheme 5: a) Mechanistic explanation for formation of ethenes 9 from dithiolanes of type 6 and b) desilylatio...
Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines
- Somaia Kamouka and
- Wesley J. Moran
Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177
- of hypervalent iodine in catalytic procedures. Studies concerning the elucidation of reaction mechanisms are ongoing and will be reported in due course. Experimental General procedure for 2-iodoanisole-catalyzed cyclization of N-propargylamide 4 or β-amidoketone 5: Propargylamide 4 (1 equiv) or β
Graphical Abstract
Scheme 1: Our previous and current iodoarene-catalyzed cyclizations.
Figure 1: Examples of biologically-active compounds containing an oxazoline ring.
Scheme 2: 2-Iodoanisole-catalyzed cyclization of N-propargylamides.
Scheme 3: Postulated mechanism for N-propargylamide cyclization.
Scheme 4: Synthesis of β-amidoketones 5.
Scheme 5: 2-Iodoanisole-catalyzed cyclization of β-amidoketones 5.
Scheme 6: In situ oxazoline ring hydrolysis.
Scheme 7: Postulated mechanism for cyclization of β-amidoketones.
New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines
- Aleksey Yu. Vorob’ev,
- Vyacheslav I. Supranovich,
- Gennady I. Borodkin and
- Vyacheslav G. Shubin
Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80
- broad applications in studies of chemical and biochemical reaction mechanisms and metabolism pathways. Deuterium is the most common used isotopic label in mechanistic studies. Deuterated organic compounds are widely used in biological [1] and pharmacological [2][3][4][5] investigations. In the last
Graphical Abstract
Figure 1: pKa values for N-aminopyridinium cation hydrogen atoms according to DFT M06-2X 6-31+G(d,p) calculat...
Scheme 1: H/D exchange of N-aminopyridinium salts 1a–c and their reaction with acetylenes.
Scheme 2: Possible pathways for the formation of 8.
Figure 2: Relative stability of 3-CO2Et-substituted dihydropyrazolo[1,5-a]pyridines by the M06-2X 6-31+G(d,p)...
Scheme 3: Synthesis of deutero 1,2,4-triazolo[1,5-a]pyridines.
Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study
- Michael L. McKee,
- Grzegorz Mlostoń,
- Katarzyna Urbaniak and
- Heinz Heimgartner
Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44
- intermediate, delocalized diradical species. The influence of selenium as a ‘heavy atom’ for stabilization of this intermediate has been emphasized. Keywords: 1,3-dipolar cycloadditions; reaction mechanisms; reactive intermediates; thiocarbonyl S-methanides; thioketones; Introduction Thiocarbonyl S
- , with no exception, via a head-to-head dimerization yielding sterically crowded 1,4-dithianes of type 5 [9][10]. The analogous head-to-head dimerization course was reported for the thiocarbonyl S-methanide derived from benzyl octafluorodithiopentanoate [11]. The reaction mechanisms of the dimerization
Graphical Abstract
Scheme 1: Generation and typical reactions of the reactive dialkyl and diaryl thiocarbonyl S-methanides 1.
Figure 1: Structures of the reactive intermediates as a diradical 6 or a zwitterion 7 in the course of the di...
Scheme 2: The in situ generation of phenyl selenophen-2-yl S-methanide (8) and its competitive reactions: 1,3...
Figure 2: Potential 1,3-dipolar electrocyclization of thiocabonyl S-methanide 8A. Computed enthalpies (free e...
Figure 3: Stepwise radical dimerization of the reactive thiocarbonyl S-methanide 8. Computed enthalpies (free...
Figure 4: Potential competitive cyclization reactions of the intermediate diradical 12.
Figure 5: a) Spin densities in the conformers 12F and 12G of diradical 12. b) Heteroatom effect on the magnit...
NMR reaction monitoring in flow synthesis
- M. Victoria Gomez and
- Antonio de la Hoz
Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31
- -on-a-chip approach. Kinetic and mechanistic studies The rapid analysis produced in flow NMR can be used for the detection of reactive intermediates and consequently for studying reaction mechanisms and the rapid optimization of a chemical process. The first example was described by Nakakoshi et al
Graphical Abstract
Figure 1: Graphical representation of (a) conventional flow cell with a saddle-shaped RF coil and (b) flow ca...
Figure 2: Possible geometries of NMR coils.
Figure 3: The NMR pulse sequence used for NOESY with WET solvent suppression [28].
Figure 4: Reaction of p-phenylenediamine with isobutyraldehyde. (a) Flow tube and (b) 1H NMR stacked plot (40...
Figure 5: Scheme and experimental setup of the flow system.
Figure 6: (a) Microfluidic probe. (b) Microreactor holder. (c) Stripline NMR chip holder. (d) Arrangement of ...
Figure 7: Acetylation of benzyl alcohol. Spectra at (a) 9 s and (b) 3 min. Stoichiometry: benzyl alcohol/DIPE...
Figure 8: a) Design of MICCS and b) schematic diagram of MICCS–NMR [45]. CH2Cl2 solutions of oxime ether and trie...
Scheme 1: Proposed reaction mechanism.
Figure 9: Flowsheet of the experimental setup used to study the reaction kinetics of the oligomer formation i...
Figure 10: Design of the experimental setup used to combine on-line NMR spectroscopy and a batch reactor. Repr...
Figure 11: Reaction system 1,3-dimethylurea/formaldehyde. Main reaction pathway and side reactions [47].
Figure 12: (a) Experimental setup for the reaction. (b) Reaction samples analyzed independently by NMR. (c) Pl...
Figure 13: (a) Schematics of two microreactor cohorts of sample fractions. (b) Reaction product concentration ...
Figure 14: NMR analysis of the reaction of benzaldehyde (2 M in CH3CN) and benzylamine (2 M in CH3CN) (1:1), r...
Figure 15: Flow diagram showing the self-optimizing reactor system. Reproduced with permission from reference [50]...
Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles
- Patrick T. Campos,
- Leticia V. Rodrigues,
- Andrei L. Belladona,
- Caroline R. Bender,
- Juliana S. Bitencurt,
- Fernanda A. Rosa,
- Davi F. Back,
- Helio G. Bonacorso,
- Nilo Zanatta,
- Clarissa P. Frizzo and
- Marcos A. P. Martins
Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29
- intermediates, and from these data it was possible to explain the regiochemistry of the products obtained. Additionally, the data were a useful tool for elucidating the reaction mechanisms. Keywords: DFT-B3LYP; polyazaheterocycles; pyrazinone; pyrido[1,2-a]pyrimidinone; pyrimido[1,2-a]benzimidazole
Graphical Abstract
Scheme 1: Mechanism proposed for the formation of compound 5.
Scheme 2: Mechanism proposed for the formation of compound 9a.
Figure 1: ORTEP plot of 6, 9c, and 12g with the thermal ellipsoids drawn at the following probability levels:...
Self-optimisation and model-based design of experiments for developing a C–H activation flow process
- Alexander Echtermeyer,
- Yehia Amar,
- Jacek Zakrzewski and
- Alexei Lapkin
Beilstein J. Org. Chem. 2017, 13, 150–163, doi:10.3762/bjoc.13.18
- design the most informative experiments. This approach requires some model structures to be known a priori which may restrict the methodology to reactions with known mechanism, or to empirical parametric models. A discussion of how a priori knowledge of chemistry, i.e., reaction mechanisms, is included
Graphical Abstract
Figure 1: A framework of closed-loop or self-optimisation combining smart DoE algorithms, process analytics, ...
Scheme 1: Catalytic reaction scheme showing C–H activation of an aliphatic secondary amine 1 to form the azir...
Scheme 2: A simplified reaction mechanism based on literature [21], showing intermediate B and the side reaction ...
Figure 2: Schematics of the automated continuous-flow system used for model development and ‘black-box’ seque...
Figure 3: Results of experiments from the MBDoE in Table 2, conducted for parameter estimation, and their correspond...
Figure 4: Results of in silico iterations of the multi-objective active learner (MOAL) algorithm [26]. Each itera...
Figure 5: Results of the optimisation driven by a statistical algorithm and in the absence of a physical proc...
New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation
- Pavel Nagorny and
- Zhankui Sun
Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283
- ][76][77][78][79]. Interestingly, such reaction mechanisms are not well understood, and the formation of trace quantities of hydroiodic acid rather than the direct substrate activation by molecular iodine has been frequently invoked to rationalize the outcome of these studies. Recently, Breugst and co
Graphical Abstract
Figure 1: Electrophile Activation by Hydrogen Bond Donors [1-16].
Figure 2: Early examples of C–H hydrogen bonds and their recent use in supramolecular chemistry [18,19,32-34].
Scheme 1: Design of 1,2,3-triazole-based catalysts for trityl group transfer through chloride anion binding b...
Scheme 2: Examples of chiral triazole-based catalysts for anion activation designed by Mancheno and co-worker...
Scheme 3: Application of chiral triazole-based catalysts L3 and L4 for counterion activation of pyridinium, q...
Scheme 4: Ammonium salt anion binding via C–H hydrogen bonds in solid state [40-45,50,51].
Scheme 5: Early examples of ammonium salts being used for electrophilic activation of imines in aza-Diels–Ald...
Scheme 6: Ammonium salts as hydrogen bond-donor catalysts by Bibal and co-workers [53,54].
Scheme 7: Tetraalkylammonium catalyst (L6)-catalyzed dearomatization of isoquinolinium salts [50].
Scheme 8: Tetraalkylammonium catalyst L6 complexation to halogen-containing substrates [51].
Scheme 9: Tetraalkylammonium-catalyzed aza-Diels–Alder reaction by Maruoka and co-workers [52].
Scheme 10: (A) Alkylpyridinium catalysts L13-catalyzed reaction of 1-isochroman and silyl ketene acetals by Be...
Scheme 11: Mixed N–H/C–H two hydrogen bond donors L14 and L15 as organocatalysts for ROP of lactide by Bibal a...
Scheme 12: Examples of stable complexes based on halogen bonding [68,69].
Scheme 13: Interaction between (−)-sparteine hydrobromide and (S)-1,2-dibromohexafluoropropane in the cocrysta...
Scheme 14: Iodine-catalyzed reactions that are computationally proposed to proceed through halogen bond to car...
Scheme 15: Transfer hydrogenation of phenylquinolines catalyzed by haloperfluoroalkanes by Bolm and co-workers ...
Scheme 16: Halogen bond activation of benzhydryl bromides by Huber and co-workers [82].
Scheme 17: Halogen bond-donor-catalyzed addition to oxocarbenium ions by Huber and co-workers [89].
Scheme 18: Halogen bond-donor activation of α,β-unsaturated carbonyl compounds in the [2 + 4] cycloaddition re...
Scheme 19: Halogen bond donor activation of imines in the [2 + 4] cycloaddition reaction of imine and Danishef...
Scheme 20: Transfer hydrogenation catalyzed by a chiral halogen bond donor by Tan and co-workers [91].
Scheme 21: Allylation of benzylic alcohols by Takemoto and co-workers [92].
Scheme 22: NIS induced semipinacol rearrangement via C–X bond cleavage [93].
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
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 ...
Organometallic chemistry
- Bernd F. Straub,
- Rolf Gleiter,
- Claudia Meier and
- Lutz H. Gade
Beilstein J. Org. Chem. 2016, 12, 2216–2221, doi:10.3762/bjoc.12.213
- investigation of more active and more selective homogeneous catalysts, catalytic transformations in the total synthesis of natural products, the theoretical and kinetic unravelling of reaction mechanisms, and the verification of rare coordination modes. These various facets underline the importance of
Figure 1: Peter Hofmann.
A flow reactor setup for photochemistry of biphasic gas/liquid reactions
- Josef Schachtner,
- Patrick Bayer and
- Axel Jacobi von Wangelin
Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170
- considered that potential excitation of other reagents could trigger competitive reaction mechanisms and pathways. The LEDs were mounted on an aluminium rod which is water-cooled from the interior to prevent (over-)heating of the LEDs and the reaction (Figure 3). White light was obtained from a commercial
Graphical Abstract
Figure 1: The challenge of mixing the three dispersed entities gas, liquid, and light for photochemical appli...
Scheme 1: Mutual interdependencies of critical reaction and reactor parameters.
Scheme 2: Blueprint of the home-built microflow photoreactor; schematic illustration of the reactor setup wit...
Figure 2: Total absorbance of methylene blue solutions in acetonitrile according to the Beer-Lambert law: Eλ ...
Figure 3: Red (λmax = 633 nm), blue (λmax = 448 nm), green (λmax = 520 nm) and white (λmax = 620 nm) LEDs mou...
Figure 4: Overlap of absorption spectrum of methylene blue in acetonitrile and emission spectra of reasonably...
Figure 5: Emission spectra of different LEDs; red (λmax = 633 nm), blue (λmax = 448 nm), green (λmax = 520 nm...
Scheme 3: Slug flow conditions of two-phase gas-liquid mixtures. Photograph of a slug flow of a solution of m...
Figure 6: Photograph of the operating flow reactor, irradiated with white LEDs, filled with a solution of met...
Scheme 4: Schematic illustration of a reactor tube (length l, inner diameter d) and pressure gradient Δp acco...
Scheme 5: Reaction types of organic molecules with singlet oxygen.
Figure 7: Home-made flow reactor and peripheral devices for photochemical reactions at light/liquid/gas inter...
Scheme 6: Photooxygenation of N-methyl-1,2,3,6-tetrahydrophthalimide and reductive work-up to alcohol 3a.
Figure 8: Conversion vs methylene blue sensitizer concentration. Reactions at constant flow rates in acetonit...
Figure 9: Reaction progress at different residence times in flow and batch reactions. Flow: reactions at diff...
Scheme 7: Oxidation of N-methyl-1,2,3,6-tetrahydro-3-acetamidophthalimide and reductive work-up to alcohol 3b....
Rearrangements of organic peroxides and related processes
- Ivan A. Yaremenko,
- Vera A. Vil’,
- Dmitry V. Demchuk and
- Alexander O. Terent’ev
Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162
Graphical Abstract
Figure 1: The named transformations considered in this review.
Scheme 1: The Baeyer–Villiger oxidation.
Scheme 2: The general mechanism of the peracid-promoted Baeyer–Villiger oxidation.
Scheme 3: General mechanism of the Lewis acid-catalyzed Baeyer–Villiger rearrangement.
Scheme 4: The theoretically studied mechanism of the BV oxidation reaction promoted by H2O2 and the Lewis aci...
Scheme 5: Proton movements in the transition states of the Baeyer–Villiger oxidation.
Scheme 6: The dependence of the course of the Baeyer–Villiger oxidation on the type of O–O-bond cleavage in t...
Scheme 7: The acid-catalyzed Baeyer–Villiger oxidation of cyclic epoxy ketones 22.
Scheme 8: Oxidation of isophorone oxide 29.
Scheme 9: Synthesis of acyl phosphate 32 from acyl phosphonate 31.
Scheme 10: Synthesis of aflatoxin B2 (36).
Scheme 11: The Baeyer–Villiger rearrangement of ketones 37 to lactones 38.
Scheme 12: Synthesis of 3,4-dimethoxybenzoic acid (40) via Baeyer–Villiger oxidation.
Scheme 13: Oxone transforms α,β-unsaturated ketones 43 into vinyl acetates 44.
Scheme 14: The Baeyer–Villiger oxidation of ketones 45 using diaryl diselenide and hydrogen peroxide.
Scheme 15: Baeyer–Villiger oxidation of (E)-2-methylenecyclobutanones.
Scheme 16: Oxidation of β-ionone (56) by H2O2/(BnSe)2 with formation of (E)-2-(2,6,6-trimethylcyclohex-1-en-1-...
Scheme 17: The mechanism of oxidation of ketones 58a–f by hydrogen peroxide in the presence of arsonated polys...
Scheme 18: Oxidation of ketone (58b) by H2O2 to 6-methylcaprolactone (59b) catalyzed by Pt complex 66·BF4.
Scheme 19: Oxidation of ketones 67 with H2O2 in the presence of [(dppb}Pt(µ-OH)]22+.
Scheme 20: The mechanism of oxidation of ketones 67 in the presence of [(dppb}Pt(µ-OH)]22+ and H2O2.
Scheme 21: Oxidation of benzaldehydes 69 in the presence of the H2O2/MeReO3 system.
Scheme 22: Oxidation of acetophenones 72 in the presence of the H2O2/MeReO3 system.
Scheme 23: Baeyer–Villiger oxidation of 2-adamantanone (45c) in the presence of Sn-containing mesoporous silic...
Scheme 24: Aerobic Baeyer–Villiger oxidation of ketones 76 using metal-free carbon.
Scheme 25: A regioselective Baeyer-Villiger oxidation of functionalized cyclohexenones 78 into a dihydrooxepin...
Scheme 26: The oxidation of aldehydes and ketones 80 by H2O2 catalyzed by Co4HP2Mo15V3O62.
Scheme 27: The cleavage of ketones 82 with hydrogen peroxide in alkaline solution.
Scheme 28: Oxidation of ketones 85 to esters 86 with H2O2–urea in the presence of KHCO3.
Scheme 29: Mechanism of the asymmetric oxidation of cyclopentane-1,2-dione 87a with the Ti(OiPr)4/(+)DET/t-BuO...
Scheme 30: The oxidation of cis-4-tert-butyl-2-fluorocyclohexanone (93) with m-chloroperbenzoic acid.
Scheme 31: The mechanism of the asymmetric oxidation of 3-substituted cyclobutanone 96a in the presence of chi...
Scheme 32: Enantioselective Baeyer–Villiger oxidation of cyclic ketones 98.
Scheme 33: Regio- and enantioselective Baeyer–Villiger oxidation of cyclic ketones 101.
Scheme 34: The proposed mechanism of the Baeyer–Villiger oxidation of acetal 105f.
Scheme 35: Synthesis of hydroxy-10H-acridin-9-one 117 from tetramethoxyanthracene 114.
Scheme 36: The Baeyer–Villiger oxidation of the fully substituted pyrrole 120.
Scheme 37: The Criegee rearrangement.
Scheme 38: The mechanism of the Criegee reaction of a peracid with a tertiary alcohol 122.
Scheme 39: Criegee rearrangement of decaline ethylperoxoate 127 into ketal 128.
Scheme 40: The ionic cleavage of 2-methoxy-2-propyl perester 129.
Scheme 41: The Criegee rearrangement of α-methoxy hydroperoxide 136.
Scheme 42: Synthesis of enol esters and acetals via the Criegee rearrangement.
Scheme 43: Proposed mechanism of the transformation of 1-hydroperoxy-2-oxabicycloalkanones 147a–d.
Scheme 44: Transformation of 3-hydroxy-1,2-dioxolanes 151 into diketone derivatives 152.
Scheme 45: Criegee rearrangement of peroxide 153 with the mono-, di-, and tri-O-insertion.
Scheme 46: The sequential Criegee rearrangements of adamantanes 157a,b.
Scheme 47: Synthesis of diaryl carbonates 160a–d from triarylmethanols 159a–d through successive oxygen insert...
Scheme 48: The synthesis of sesquiterpenes 162 from ketone 161 with a Criegee rearrangement as one key step.
Scheme 49: Synthesis of trans-hydrindan derivatives 164, 165.
Scheme 50: The Hock rearrangement.
Scheme 51: The general scheme of the cumene process.
Scheme 52: The Hock rearrangement of aliphatic hydroperoxides.
Scheme 53: The mechanism of solvolysis of brosylates 174a–c and spiro cyclopropyl carbinols 175a–c in THF/H2O2....
Scheme 54: The fragmentation mechanism of hydroperoxy acetals 178 to esters 179.
Scheme 55: The acid-catalyzed rearrangement of phenylcyclopentyl hydroperoxide 181.
Scheme 56: The peroxidation of tertiary alcohols in the presence of a catalytic amount of acid.
Scheme 57: The acid-catalyzed reaction of bicyclic secondary alcohols 192 with hydrogen peroxide.
Scheme 58: The photooxidation of 5,6-disubstituted 3,4-dihydro-2H-pyrans 196.
Scheme 59: The oxidation of tertiary alcohols 200a–g, 203a,b, and 206.
Scheme 60: Transformation of functional peroxide 209 leading to 2,3-disubstitued furans 210 in one step.
Scheme 61: The synthesis of carbazoles 213 via peroxide rearrangement.
Scheme 62: The construction of C–N bonds using the Hock rearrangement.
Scheme 63: The synthesis of moiety 218 from 217 which is a structural motif in the antitumor–antibiotic of CC-...
Scheme 64: The in vivo oxidation steps of cholesterol (219) by singlet oxygen.
Scheme 65: The proposed mechanism of the rearrangement of cholesterol-5α-OOH 220.
Scheme 66: Photochemical route to artemisinin via Hock rearrangement of 223.
Scheme 67: The Kornblum–DeLaMare rearrangement.
Scheme 68: Kornblum–DeLaMare transformation of 1-phenylethyl tert-butyl peroxide (225).
Scheme 69: The synthesis 4-hydroxyenones 230 from peroxide 229.
Scheme 70: The Kornblum–DeLaMare rearrangement of peroxide 232.
Scheme 71: The reduction of peroxide 234.
Scheme 72: The Kornblum–DeLaMare rearrangement of endoperoxide 236.
Scheme 73: The rearrangement of peroxide 238 under Kornblum–DeLaMare conditions.
Scheme 74: The proposed mechanism of rearrangement of peroxide 238.
Scheme 75: The Kornblum–DeLaMare rearrangement of peroxides 242a,b.
Scheme 76: The base-catalyzed rearrangements of bicyclic endoperoxides having electron-withdrawing substituent...
Scheme 77: The base-catalyzed rearrangements of bicyclic endoperoxides 249a,b having electron-donating substit...
Scheme 78: The base-catalyzed rearrangements of bridge-head substituted bicyclic endoperoxides 251a,b.
Scheme 79: The Kornblum–DeLaMare rearrangement of hydroperoxide 253.
Scheme 80: Synthesis of β-hydroxy hydroperoxide 254 from endoperoxide 253.
Scheme 81: The amine-catalyzed rearrangement of bicyclic endoperoxide 263.
Scheme 82: The base-catalyzed rearrangement of meso-endoperoxide 268 into 269.
Scheme 83: The photooxidation of 271 and subsequent Kornblum–DeLaMare reaction.
Scheme 84: The Kornblum–DeLaMare rearrangement as one step in the oxidation reaction of enamines.
Scheme 85: The Kornblum–DeLaMare rearrangement of 3,5-dihydro-1,2-dioxenes 284, 1,2-dioxanes 286, and tert-but...
Scheme 86: The Kornblum–DeLaMare rearrangement of epoxy dioxanes 290a–d.
Scheme 87: Rearrangement of prostaglandin H2 292.
Scheme 88: The synthesis of epicoccin G (297).
Scheme 89: The Kornblum–DeLaMare rearrangement used in the synthesis of phomactin A.
Scheme 90: The Kornblum–DeLaMare rearrangement in the synthesis of 3H-quinazolin-4-one 303.
Scheme 91: The Kornblum–DeLaMare rearrangement in the synthesis of dolabriferol (308).
Scheme 92: Sequential transformation of 3-substituted 2-pyridones 309 into 3-hydroxypyridine-2,6-diones 311 in...
Scheme 93: The Kornblum–DeLaMare rearrangement of peroxide 312 into hydroxy enone 313.
Scheme 94: The Kornblum–DeLaMare rearrangement in the synthesis of polyfunctionalized carbonyl compounds 317.
Scheme 95: The Kornblum–DeLaMare rearrangement in the synthesis of (Z)-β-perfluoroalkylenaminones 320.
Scheme 96: The Kornblum–DeLaMare rearrangement in the synthesis of γ-ketoester 322.
Scheme 97: The Kornblum–DeLaMare rearrangement in the synthesis of diterpenoids 326 and 328.
Scheme 98: The synthesis of natural products hainanolidol (331) and harringtonolide (332) from peroxide 329.
Scheme 99: The synthesis of trans-fused butyrolactones 339 and 340.
Scheme 100: The synthesis of leucosceptroid C (343) and leucosceptroid P (344) via the Kornblum–DeLaMare rearra...
Scheme 101: The Dakin oxidation of arylaldehydes or acetophenones.
Scheme 102: The mechanism of the Dakin oxidation.
Scheme 103: A solvent-free Dakin reaction of aromatic aldehydes 356.
Scheme 104: The organocatalytic Dakin oxidation of electron-rich arylaldehydes 358.
Scheme 105: The Dakin oxidation of electron-rich arylaldehydes 361.
Scheme 106: The Dakin oxidation of arylaldehydes 358 in water extract of banana (WEB).
Scheme 107: A one-pot approach towards indolo[2,1-b]quinazolines 364 from indole-3-carbaldehydes 363 through th...
Scheme 108: The synthesis of phenols 367a–c from benzaldehydes 366a-c via acid-catalyzed Dakin oxidation.
Scheme 109: Possible transformation paths of the highly polarized boric acid coordinated H2O2–aldehyde adduct 3...
Scheme 110: The Elbs oxidation of phenols 375 to hydroquinones.
Scheme 111: The mechanism of the Elbs persulfate oxidation of phenols 375 affording p-hydroquinones 376.
Scheme 112: Oxidation of 2-pyridones 380 under Elbs persulfate oxidation conditions.
Scheme 113: Synthesis of 3-hydroxy-4-pyridone (384) via an Elbs oxidation of 4-pyridone (382).
Scheme 114: The Schenck rearrangement.
Scheme 115: The Smith rearrangement.
Scheme 116: Three main pathways of the Schenck rearrangement.
Scheme 117: The isomerization of hydroperoxides 388 and 389.
Scheme 118: Trapping of dioxacyclopentyl radical 392 by oxygen.
Scheme 119: The hypothetical mechanism of the Schenck rearrangement of peroxide 394.
Scheme 120: The autoxidation of oleic acid (397) with the use of labeled isotope 18O2.
Scheme 121: The rearrangement of 18O-labeled hydroperoxide 400 under an atmosphere of 16O2.
Scheme 122: The rearrangement of the oleate-derived allylic hydroperoxides (S)-421 and (R)-425.
Scheme 123: Mechanisms of Schenck and Smith rearrangements.
Scheme 124: The rearrangement and cyclization of 433.
Scheme 125: The Wieland rearrangement.
Scheme 126: The rearrangement of bis(triphenylsilyl) 439 or bis(triphenylgermyl) 441 peroxides.
Scheme 127: The oxidative transformation of cyclic ketones.
Scheme 128: The hydroxylation of cyclohexene (447) in the presence of tungstic acid.
Scheme 129: The oxidation of cyclohexene (447) under the action of hydrogen peroxide.
Scheme 130: The reaction of butenylacetylacetone 455 with hydrogen peroxide.
Scheme 131: The oxidation of bridged 1,2,4,5-tetraoxanes.
Scheme 132: The proposed mechanism for the oxidation of bridged 1,2,4,5-tetraoxanes.
Scheme 133: The rearrangement of ozonides.
Scheme 134: The acid-catalyzed oxidative rearrangement of malondialdehydes 462 under the action of H2O2.
Scheme 135: Pathways of the Lewis acid-catalyzed cleavage of dialkyl peroxides 465 and ozonides 466.
Scheme 136: The mechanism of the transformation of (tert-butyldioxy)cyclohexanedienones 472.
Scheme 137: The synthesis of Vitamin K3 from 472a.
Scheme 138: Proposed mechanism for the transformation of 478d into silylated endoperoxide 479d.
Scheme 139: The rearrangement of hydroperoxide 485 to form diketone 486.
Scheme 140: The base-catalyzed rearrangement of cyclic peroxides 488a–g.
Scheme 141: Synthesis of chiral epoxides and aldols from peroxy hemiketals 491.
Scheme 142: The multistep transformation of (R)-carvone (494) to endoperoxides 496a–e.
Scheme 143: The decomposition of anthracene endoperoxide 499.
Scheme 144: Synthesis of esters 503 from aldehydes 501 via rearrangement of peroxides 502.
Scheme 145: Two possible paths for the base-promoted decomposition of α-azidoperoxides 502.
Scheme 146: The Story decomposition of cyclic diperoxide 506a.
Scheme 147: The Story decomposition of cyclic triperoxide 506b.
Scheme 148: The thermal rearrangement of endoperoxides A into diepoxides B.
Scheme 149: The transformation of peroxide 510 in the synthesis of stemolide (511).
Scheme 150: The possible mechanism of the rearrangement of endoperoxide 261g.
Scheme 151: The photooxidation of indene 517.
Scheme 152: The isomerization of ascaridole (523).
Scheme 153: The isomerization of peroxide 525.
Scheme 154: The thermal transformation of endoperoxide 355.
Scheme 155: The photooxidation of cyclopentadiene (529) at a temperature higher than 0 °C.
Scheme 156: The thermal rearrangement of endoperoxides 538a,b.
Scheme 157: The transformation of peroxides 541.
Scheme 158: The thermal rearrangements of strained cyclic peroxides.
Scheme 159: The thermal rearrangement of diacyl peroxide 551 in the synthesis of C4-epi-lomaiviticin B core 553....
Scheme 160: The 1O2 oxidation of tryptophan (554) and rearrangement of dioxetane intermediate 555.
Scheme 161: The Fe(II)-promoted cleavage of aryl-substituted bicyclic peroxides.
Scheme 162: The proposed mechanism of the Fe(II)-promoted rearrangement of 557a–c.
Scheme 163: The reaction of dioxolane 563 with Fe(II) sulfate.
Scheme 164: Fe(II)-promoted rearrangement of 1,2-dioxane 565.
Scheme 165: Fe(II) cysteinate-promoted rearrangement of 1,2-dioxolane 568.
Scheme 166: The transformation of 1,2-dioxanes 572a–c under the action of FeCl2.
Scheme 167: Fe(II) cysteinate-promoted transformation of tetraoxane 574.
Scheme 168: The CoTPP-catalyzed transformation of bicyclic endoperoxides 600a–d.
Scheme 169: The CoTPP-catalyzed transformation of epoxy-1,2-dioxanes.
Scheme 170: The Ru(II)-catalyzed reactions of 1,4-endoperoxide 261g.
Scheme 171: The Ru(II)-catalyzed transformation as a key step in the synthesis of elyiapyrone A (610) from 1,4-...
Scheme 172: Peroxides with antimalarial activity.
Scheme 173: The interaction of iron ions with artemisinin (616).
Scheme 174: The interaction of FeCl2 with 1,2-dioxanes 623, 624.
Scheme 175: The mechanism of reaction 623 and 624 with Fe(II)Cl2.
Scheme 176: The reaction of bicyclic natural endoperoxides G3-factors 631–633 with FeSO4.
Scheme 177: The transformation of terpene cardamom peroxide 639.
Scheme 178: The different ways of the cleavage of tetraoxane 643.
Scheme 179: The LC–MS analysis of interaction of tetraoxane 646 with iron(II)heme 647.
Scheme 180: The rearrangement of 3,6-epidioxy-1,10-bisaboladiene (EDBD, 649).
Scheme 181: Easily oxidized substrates.
Scheme 182: Biopathway of synthesis of prostaglandins.
Scheme 183: The reduction and rearrangements of isoprostanes.
Scheme 184: The partial mechanism for linoleate 658 oxidation.
Scheme 185: The transformation of lipid hydroperoxide.
Scheme 186: The acid-catalyzed cleavage of the product from free-radical oxidation of cholesterol (667).
Scheme 187: Two pathways of catechols oxidation.
Scheme 188: Criegee-like or Hock-like rearrangement of the intermediate hydroperoxide 675 in dioxygenase enzyme...
Scheme 189: Carotinoides 679 cleavage by carotenoid cleavage dioxygenases.
Cp2TiCl/D2O/Mn, a formidable reagent for the deuteration of organic compounds
- Antonio Rosales and
- Ignacio Rodríguez-García
Beilstein J. Org. Chem. 2016, 12, 1585–1589, doi:10.3762/bjoc.12.154
- multiple applications of the deuterated compound such as the enhancement of the metabolic stability of pharmaceutical drugs, the use of internal standards for mass spectrometry, the elucidation of biosynthetic pathways, and the study of reaction mechanisms and selectivity control reactions. In an effort to
Graphical Abstract
Scheme 1: Formation of reaction intermediates susceptible of being reduced by Cp2TiCl/Mn/D2O.
Scheme 2: Proposed reduction of radicals via hydrolysis of an organometalic alkyl-TiIV or as DAT.
Scheme 3: Examples of deuterations of organic compounds using Cp2TiCl/D2O/Mn. aSubstoichiometric amount of Cp2...
One-pot synthesis of 4′-alkyl-4-cyanobiaryls on the basis of the terephthalonitrile dianion and neutral aromatic nitrile cross-coupling
- Roman Yu. Peshkov,
- Elena V. Panteleeva,
- Wang Chunyan,
- Evgeny V. Tretyakov and
- Vitalij D. Shteingarts
Beilstein J. Org. Chem. 2016, 12, 1577–1584, doi:10.3762/bjoc.12.153
- mechanisms within cross-coupling: heterolytic addition of dianion 12− (SNH) to nitrile 2, and/or electron transfer from 12− to 2 followed by recombination or relaxation in the primary pair of radical anions 1·− and 2·− (Scheme 2). These probable reaction mechanisms were studied in [23][24] and are beyond
Graphical Abstract
Scheme 1: The main synthetic approaches to alkylcyanobiphenyls.
Scheme 2: Para-cyanophenylation of substituted benzonitriles 2 by dianion 12− with the formation of a long-li...
Scheme 3: para-Cyanophenylation of 1-cyanonaphthalene 5i by dianion 12− with subsequent butylation providing ...
Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides
- Franziska Hemmerling and
- Frank Hahn
Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148
- any cofactors, in spite of its flavin adenine dinucleotide (FAD) binding site [98][99]. The reaction mechanisms and biosynthetic enzymes involved in the rearrangement of versicolorin B (106) to demethylsterigmatocystin (107) have also been discussed controversely. Up to four genes (aflM, aflN, aflX
Graphical Abstract
Scheme 1: Schematic description of the cyclisation reaction catalysed by TE domains. In most cases, the nucle...
Scheme 2: Mechanisms for the formation of oxygen heterocycles. The degree of substitution can differ from tha...
Scheme 3: Pyran-ring formation in pederin (24) biosynthesis. Incubation of recombinant PedPS7 with substrate ...
Scheme 4: The domain AmbDH3 from ambruticin biosynthesis catalyses the dehydration of 25 and subsequent cycli...
Scheme 5: SalBIII catalyses dehydration of 29 and subsequent cyclisation to tetrahydropyran 30 [18].
Figure 1: All pyranonaphtoquinones contain either the naphtha[2,3-c]pyran-5,10-dione (32) or the regioisomeri...
Scheme 6: Pyran-ring formation in actinorhodin (34) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H...
Scheme 7: Pyran formation in granaticin (36) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H-napht...
Scheme 8: Pyran formation in alnumycin (37) biosynthesis. Adapted from [21].
Scheme 9: Biosynthesis of pseudomonic acid A (61). The pyran ring is initially formed in 57 after dehydrogena...
Scheme 10: Epoxidation–cyclisation leads to the formation of the tetrahydropyran ring in the western part of t...
Scheme 11: a) Nonactin (70) is formed from heterodimers of (−)(+)-dimeric nonactic acid and (+)(−)-dimeric non...
Figure 2: Pamamycins (73) are macrodiolide antibiotics containing three tetrahydrofuran moieties, which are a...
Scheme 12: A PS domain homolog in oocydin A (76) biosynthesis is proposed to catalyse furan formation via an o...
Scheme 13: Mechanism of oxidation–furan cyclisation by AurH, which converts (+)-deoxyaureothin (77) into (+)-a...
Scheme 14: Leupyrrin A2 (80) and the proposed biosynthesis of its furylidene moiety [69,70].
Scheme 15: Asperfuranone (93) biosynthesis, adapted from [75].
Figure 3: The four major aflatoxins produced by Aspergilli are the types B1, B2, G1 and G2 (94–97). In the di...
Scheme 16: Overview on aflatoxin B1 (94) biosynthesis. HOMST = 11-hydroxy-O-methylsterigmatocystin [78,79,82-106].
Scheme 17: A zipper mechanism leads to the formation of oxygen heterocycles in monensin biosynthesis [109-111].
Scheme 18: Formation of the 2,6-dioxabicyclo[3.2.1]octane (DBO) ring system in aurovertin B (118) biosynthesis ...
Figure 4: Structures of the epoxide-containing polyketides epothilone A (119) and oleandomycin (120) [123-125].
Scheme 19: Structures of phoslactomycin B (121) (a) and jerangolid A (122) (b). The heterocycle-forming steps ...
Scheme 20: a) Structures of rhizoxin (130) and cycloheximide (131). Model for the formation of δ-lactones (b) ...
Scheme 21: EncM catalyses a dual oxidation sequence and following processing of the highly reactive intermedia...
Figure 5: Mesomeric structures of tetronates [138,139].
Figure 6: Structures of tetronates for which gene clusters have been sequenced. The tetronate moiety is shown...
Scheme 22: Conserved steps for formation and processing in several 3-acyl-tetronate biosynthetic pathways were...
Scheme 23: In versipelostatin A (153) biosynthesis, VstJ is a candidate enzyme for catalysing the [4 + 2] cycl...
Scheme 24: a) Structures of some thiotetronate antibiotics. b) Biosynthesis of thiolactomycin (165) as propose...
Scheme 25: Aureusidine synthase (AS) catalyses phenolic oxidation and conjugate addition of chalcones leading ...
Scheme 26: a) Oxidative cyclisation is a key step in the biosynthesis of spirobenzofuranes 189, 192 and 193. b...
Scheme 27: A bicyclisation mechanism forms a β-lactone and a pyrrolidinone and removes the precursor from the ...
Scheme 28: Spontaneous cyclisation leads to off-loading of ebelactone A (201) from the PKS machinery [163].
Scheme 29: Mechanisms for the formation of nitrogen heterocycles.
Scheme 30: Biosynthesis of highly substituted α-pyridinones. a) Feeding experiments confirmed the polyketide o...
Scheme 31: Acridone synthase (ACS) catalyses the formation of 1,3-dihydroxy-N-methylacridone (224) by condensa...
Scheme 32: A Dieckmann condensation leads to the formation of a 3-acyl-4-hydroxypyridin-2-one 227 and removes ...
Scheme 33: a) Biosynthesis of the pyridinone tenellin (234). b) A radical mechanism was proposed for the ring-...
Scheme 34: a) Oxazole-containing PKS–NRPS-derived natural products oxazolomycin (244) and conglobatin (245). b...
Scheme 35: Structure of tetramic acids 251 (a) and major tautomers of 3-acyltetramic acids 252a–d (b). Adapted...
Scheme 36: Equisetin biosynthesis. R*: terminal reductive domain. Adapted from [202].
Scheme 37: a) Polyketides for which a similar biosynthetic logic was suggested. b) Pseurotin A (256) biosynthe...
Figure 7: Representative examples of PTMs with varying ring sizes and oxidation patterns [205,206].
Scheme 38: Ikarugamycin biosynthesis. Adapted from [209-211].
Scheme 39: Tetramate formation in pyrroindomycin aglycone (279) biosynthesis [213-215].
Scheme 40: Dieckmann cyclases catalyse tetramate or 2-pyridone formation in the biosynthesis of, for example, ...
