Synthesis of the Anti‐HIV Agent (−)‐Hyperolactone C by Using Oxonium Ylide Formation–Rearrangement

Starting from readily available (S)‐styrene oxide an asymmetric synthesis is described of the naturally occurring anti‐HIV spirolactone (?)‐hyperolactone C, which possesses adjacent fully substituted stereocenters. The key step involves a stereocontrolled Rh^II‐catalysed oxonium ylide formation–[2,3] sigmatropic rearrangement of an α‐diazo‐β‐ketoester bearing allylic ether functionality. From the resulting furanone, an acid‐catalysed lactonisation and dehydrogenation gives the natural product.     

1,4‐Cyclohexadienes—Easy Access to a Versatile Building Block via Transition‐Metal‐Catalysed Diels–Alder Reactions

1,4‐Cyclohexadiene derivatives are easily accessed via transition‐metal cycloadditions of 1,3‐dienes with alkynes. The mild reaction conditions of several transition‐metal‐catalysed reactions allows the incorporation of various functional groups to access functionalised 1,4‐cyclohexadienes. The control of the regiochemistry in the intermolecular cobalt‐catalysed Diels–Alder reaction is realised utilising different ligand designs. The functionalised 1,4‐cyclohexadiene derivatives are valuable building blocks in follow‐up transformations. Finally, the oxidation of the 1,4‐cyclohexadienes can be accomplished under mild conditions to generate the corresponding arene derivatives.     

Total Synthesis and Absolute Configuration Assignment of MRSA Active Garcinol and Isogarcinol

A short total synthesis of (±)‐garcinol and (±)‐isogarcinol, two endo‐type B PPAPs with reported activity against methiciline resistant Staphylococcus aureus (MRSA), is presented. The separation of framework‐constructing from framework‐decorating steps and the application of two highly regio‐ and stereoselective Pd‐catalysed allylations, that is, the Pd‐catalysed decarboxylative Tsuji–Trost allylation and the diastereoselective Pd‐catalysed allyl–allyl cross‐coupling, are key elements that allowed the total synthesis to be accomplished within 13 steps starting from acetylacetone. After separation of the enantiomers the absolute configurations of the four natural products (i.e., (?)‐garcinol, (+)‐guttiferone E (i.e., ent‐garcinol), (?)‐isogarcinol, and (+)‐isoxanthochymol (i.e., ent‐isogarcinol)) were assigned based on ECD spectroscopy.     

Micellar Effect on the Reaction of Chromium(VI) Oxidation of L‐Sorbose in the Presence and Absence of Picolinic Acid in Aqueous Acid Media: A Kinetic Study

The kinetics and mechanism of chromic acid oxidation of L‐sorbose in the presence and absence of picolinic acid (PA) have been studied under the conditions, [L‐sorbose]_T » [PA]_T » [Cr(VI)]_T, at different temperatures. In the absence of PA, the monomeric chromic acid undergoes esterification with the substrate followed by the acid catalysed redox decomposition of the Cr(VI)‐substrate ester through glycol splitting to formaldehyde and the lactone of C₅‐aldonic acid and Cr(IV) which subsequently participates in the faster reactions. In the presence of PA, the Cr(VI)‐PA complex produced in a pre‐equilibrium step experiences a nucleophilic attack by the substrate to produce a ternary complex which decomposes through glycol splitting giving rise to the organic products and Cr(IV)‐PA complex. Both the uncatalysed and PA‐catalysed paths show the first‐order dependence on [L‐sorbose]_T and [Cr(VI)]_T. The PA‐catalysed path is first‐order in [PA]_T and it shows a fractional order in [H⁺]. The uncatalysed path shows a second‐order dependence on [H⁺]. In the presence of the surfactants like N‐cetylpyridinium chloride (CPC, a cationic surfactant) and sodium dodecyl sulfate (SDS, an anionic sulfate), the reaction orders remain unchanged. CPC has been found to inhibit both the uncatalysed and PA‐catalysed paths while SDS shows the rate accelerating effect for both the uncatalysed and PA‐catalysed paths. The observed micellar effects have been rationalised by considering the distribution of the reactants between the micellar and aqueous phases in terms of the proposed reaction mechanism.     

Linearly ‐π‐ extended porphyrins: Synthesis of novel tetrabenzoylporphyrins

The π‐extended porphyrins 11a – c with a λ_max = 644, 643 and 639 nm were synthesized by an acid catalysed reaction of the dipyrrolylmethane 10 with different aldehydes followed by oxidation with 2,3‐dichloro‐5,6‐dicyano‐1,4‐quinone (DDQ). In a second approach, 10 was decarboxylated to yield 12, which was treated with DMF and benzoylchloride to give the diformyl compound 13. Acid catalysed reaction of 12 and 13 led to the porphyrin 11a after oxidation.     

Enantioselective cycloadditions of 2-alkenoylpyridine-N-oxides catalysed by a bis(oxazoline)/Cu(II) complex: structure of the reactive intermediate

Diels–Alder and 1,3‐dipolar cycloadditions involving (E)‐3‐aryl‐1‐(pyridin‐2‐yl‐N‐oxide)prop‐2‐en‐1‐ones as the 2π components are efficiently catalysed by bis(oxazoline)–Cu^II complexes. The cycloadducts are obtained in quantitative yields with up to 98 % ee; absolute configurations were determined by X‐ray analysis. The structure of the reactive complex, determined by X‐ray analysis, is fully consistent with the stereochemical outcome of the catalysed process (approach of the diene or nitrone to the less hindered face of the coordinated pyridine‐N‐oxide derivative).     

Automated Generation and Reactions of 3‐Hydroxymethylindoles in Continuous‐Flow Microreactors

An automated sequential approach for the generation and reactions of 3‐hydroxymethylindoles in continuous‐flow microreactors is described. Consecutive halogen–magnesium exchanges of four 3‐iodoindoles followed by addition to three aldehydes provided twelve 3‐hydroxymethylindoles in a multi‐microreactor setup. The synthetic flow strategy could be coupled with an in line continuous liquid–liquid extraction workup protocol for each reaction. Further elaboration of each of these indoles within the fluidic setup was achieved by acid‐catalysed nucleophilic substitutions with allyltrimethylsilane and methanol used as nucleophiles. Overall, a set of four 3‐iodoindoles was converted into thirty‐six indole derivatives by a range of transformations including iodo–magnesium exchange/electrophile trapping and acid‐catalysed nucleophilic substitution in a fully automated sequential fashion.     

Rapid Assembly of Functionalised Spirocyclic Indolines by Palladium‐Catalysed Dearomatising Diallylation of Indoles with Allyl Acetate

Herein, we report the application of allyl acetate to the palladium‐catalysed dearomatising diallylation of indoles. The reaction can be carried out by using a readily available palladium catalyst at room temperature, and can be applied to a wide range of substituted indoles to provide access to the corresponding 3,3‐diallylindolinines. These compounds are versatile synthetic intermediates that readily undergo Ugi reactions or proline‐catalysed asymmetric Mannich reactions. Alternatively, acylation of the 3,3‐diallylindolinines with an acid chloride or a chloroformate, followed by treatment with aluminium chloride, enables 2,3‐diallylindoles to be prepared. By using ring‐closing metathesis, functionalised spirocyclic indoline scaffolds can be accessed from the Ugi products, and a dihydrocarbazole can be prepared from the corresponding 2,3‐diallylindole.     

Carbophilic 3‐Component Cascades: Access to Complex Bioactive Cyclopropyl Diindolylmethanes

Naturally occurring indole‐3‐carbinol and 3,3‐diindolylmethane show bioactivity in a number of disparate disease areas, including cancer, prompting substantial synthetic analogue activity. We describe a new approach to highly functionalised derivatives that starts from allene gas and proceeds via the combination of a three‐component Pd⁰‐catalysed cascade with a one‐pot, three‐component carbophilic Pt^II cascade linked to a stereoselective acid‐catalysed Mannich–Michael reaction that generates complex cyclopropyl diindolylmethanes which show selective activity against prostate cancer cell lines.     

Multicomponent Synthesis of Isoindolinone Frameworks via RhIII‐Catalysed in situ Directing Group‐Assisted Tandem Oxidative Olefination/Michael Addition

A Rh^III‐catalysed three‐component synthesis of isoindolinone frameworks via direct assembly of benzoyl chlorides, o‐aminophenols and activated alkenes has been developed. The process involves in situ generation of o‐aminophenol (OAP)‐based bidentate directing group (DG), Rh^III‐catalysed tandem ortho C?H olefination and subsequent cyclization via aza‐Michael addition. This protocol exhibits good chemoselectivity and functional group tolerance. Computational studies showed that the presence of hydroxyl group on the N‐aryl ring could enhance the chemoselectivity of the reaction.     

Recent developments in cyclodextrin‐mediated aqueous biphasic hydroformylation and tsuji–trost reactions

New cyclodextrin‐based systems have recently been developed for aqueous organometallic catalysis. Through this review, the major advances made in the field are commented upon and discussed. The role of cyclodextrins as mass transfer promoters, molecular platforms, building blocks for the formation of Pickering emulsions and thermoresponsive catalytic systems is especially emphasized. The catalytic performances of these cyclodextrin‐based catalytic systems are highlighted in two model reactions, namely the rhodium‐catalysed hydroformylation of terminal olefins and the palladium‐catalysed cleavage of allyl carbonates (Tsuji–Trost reaction). Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis of four series of quinoline‐based heterocycles by reacting 2‐chloroquinoline‐3‐carbonitriles with various types of isocyanides

Four distinct sets of functionalized quinolines were synthesized by reacting 2‐chloroquinoline‐3‐carbonitriles with various types of isocyanides under appropriate conditions. The palladium‐catalysed reaction of less hindered aliphatic and aromatic isocyanides with 2‐chloroquinoline‐3‐carbonitriles yielded 2‐alkyl(aryl)‐1‐imino‐1H‐pyrrolo[3,4‐b]quinolin‐3(2H)‐one derivatives; however, the catalysed reaction of more hindered isocyanides such as tert‐butyl isocyanide produced the corresponding 3‐cyanoquinoline‐2‐carboxamides. Interestingly, chloroquinoline‐3‐carbonitriles reacted with ethyl isocyanoacetate in the presence of Cs₂CO₃ to generate imidazo[1,5‐a]quinoline derivatives; notably, tosylmethyl isocyanide under the same conditions formed unprecedented 2‐tosyl‐3‐cyanoquinolines.     

Direct Detection of Key Intermediates in Rhodium(I)‐Catalyzed [2+2+2] Cycloadditions of Alkynes by ESI‐MS

The mechanism of the Rh‐catalysed [2+2+2] cycloaddition reaction of diynes with monoynes has been examined using ESI‐MS and ESI‐CID‐MS analysis. The catalytic system used consisted of the combination of a cationic rhodium(I) complex with bisphosphine ligands, which generates highly active complexes that can be detected by ESI(+) experiments. ESI‐MS on‐line monitoring has allowed the detection for the first time of all of the intermediates in the catalytic cycle, supporting the mechanistic proposal based mainly on theoretical calculations. For all ESI‐MS experiments, the structural assignments of ions are supported by tandem mass spectrometry analyses. Computer model studies based on density functional theory (DFT) support the structural proposal made for the monoyne insertion intermediate. The collective studies provide new insight into the reactivity of cationic rhodacyclopentadienes, which should facilitate the design of related rhodium‐catalysed C? C couplings.     

Ionic Liquids as Performance Additives for Electroenzymatic Syntheses

Electroenzymatic syntheses combine oxidoreductase‐catalysed reactions with electrochemical reactant supply. The use of ionic liquids as performance additives can contribute to overcoming existing limitations of these syntheses. Here, we report on the influence of different water‐miscible ionic liquids on critical parameters such as conductivity, biocatalyst activity and stability or substrate solubility for three typical electroenzymatic syntheses. In these investigations promising ionic liquids were identified and have been used as additives for batch electrolyses on preparative scale for the three electroenzymatic systems. It was possible to improve the space‐time‐yield for the electrochemical regeneration of NADPH by a factor of three. For an amino acid oxidase catalysed resolution of a methionine racemate with ferrocene‐mediated electrochemical regeneration of the enzyme‐bound cofactor FAD a 50 % increase in space time yield and 140 % increase in catalyst utilisation (TTN) were achieved. Furthermore, for the chloroperoxidase‐catalysed synthesis of (R)‐phenylmethylsulfoxide with electrochemical generation of the required cosubstrate H₂O₂ the space time yield and the catalyst utilisation were improved by a factor of up to 4.2 depending on the ionic liquids used.     

New Copper,Palladium and Nickel Catalytic Systems: An Evolution towards More Efficient Procedures

Metal‐catalysed reactions are a fundamental tool in synthetic chemistry. Increasingly challenging transformations can be accomplished only by means of certain metal catalysts. However, there still remains the need for a substantial decrease of the amount of catalyst, for better reuse or recycling of such active species, and for the avoidance of relatively toxic solvents in favour of environmentally friendly media. These facts apply to copper‐, palladium‐, and nickel‐catalysed cross‐coupling reactions, direct arylations, and oxidative processes. This account summarises our research on the last reactions, featuring an evolution towards more sustainable procedures in this field.     

Polycarbosilane‐supported titanium(IV) catalyst for Knoevenagel condensation reaction

Polycarbosilane (PCS) was synthesized by the polycondensation of trichloromethylsilane and trimethoxyvinylsilane in the presence of sodium metal. PCS has a highly crosslinked structure, high ceramic yield and high surface area. Titanium metal ion was attached to the polycarbosilane and its catalytic activity was investigated. The Knoevenagel condensation reaction catalysed by titanium‐incorporated polycarbosilane is reported. The titanium‐incorporated PCS catalysed the reaction well and with a diverse set of substrates the reaction proceeded with good yield. PCS‐supported transition metal catalysts have been prepared for the first time and used successfully in the Knoevenagel condensation reaction. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis of Quinolines via a Metal‐Catalyzed Dehydrogenative N‐Heterocyclization

Efficient ruthenium‐, rhodium‐, palladium‐, copper‐ and iridium‐catalysed methodologies have been recently developed for the synthesis of quinolines by the reaction of 2‐aminobenzyl alcohols with carbonyl compounds (aldehydes and ketones) or the related alcohols. The reaction is assumed to proceed via a sequence involving initial metal‐catalysed oxidation of 2‐aminobenzyl alcohols to the related 2‐aminobenzaldehydes, followed by cross aldol reaction with a carbonyl compound under basic conditions to afford α,β‐unsaturated carbonyl compounds. These aldehydes or ketones can be also generated in situ via dehydrogenation of the related primary and secondary alcohols. In the final step cyclodehydration of the α,β‐unsaturated carbonyl compound intermediates gives quinolines. Good yields of quinolines were also obtained by reacting 2‐nitrobenzyl alcohols and secondary alcohols in the presence of a ruthenium catalyst. Finally, aniline derivatives afforded also a useful access to quinolines by the reaction with 1,3‐propanediol or 3‐amino‐1‐propanol, or in a three‐component reaction with benzyl alcohol and aliphatic alcohols.     

Enantio‐ and Regioselective Conjugate Addition of Organometallic Reagents to Linear Polyconjugated Nitroolefins

The copper‐catalysed conjugate addition of trialkylaluminium and dialkylzinc reagents to polyconjugated nitroolefins (nitrodiene and nitroenyne derivatives) is reported. A reversed Josiphos ligand L7 allows for the selective 1,4‐ or 1,6‐addition with high enantioselectivities.     

Vacuum Surface Science Meets Heterogeneous Catalysis: Dehydrogenation of a Liquid Organic Hydrogen Carrier in the Liquid State

Ultrahigh vacuum (UHV) surface science techniques are used to study the heterogeneous catalytic dehydrogenation of a liquid organic hydrogen carrier in its liquid state close to the conditions of real catalysis. For this purpose, perhydrocarbazole (PH), otherwise volatile under UHV, is covalently linked as functional group to an imidazolium cation, forming a non‐volatile ionic liquid (IL). The catalysed dehydrogenation of the PH unit as a function of temperature is investigated for a Pt foil covered by a macroscopically thick PH‐IL film and for Pd particles suspended in the PH‐IL film, and for PH‐IL on Au as inert support. X‐ray photoelectron spectroscopy and thermal desorption spectroscopy allows us to follow in situ the catalysed transition of perhydrocarbazole to carbazole at technical reaction temperatures. The data demonstrate the crucial role of the Pt and Pd catalysts in order to shift the dehydrogenation temperature below the critical temperature of thermal decomposition.     

One‐Step SnO2 Nanotree Growth

A comparison between Au, TiO₂ and self‐catalysed growth of SnO₂ nanostructures using chemical vapour deposition is reported. TiO₂ enables growth of a nanonetwork of SnO₂, whereas self‐catalysed growth results in nanoclusters. Using Au catalyst, single‐crystalline SnO₂ nanowire trees can be grown in a one‐step process. Two types of trees are identified that differ in size, presence of a catalytic tip, and degree of branching. The growth mechanism of these nanotrees is based on branch‐splitting and self‐seeding by the catalytic tip, facilitating at least three levels of branching, namely trunk, branch and leaf.