This review is an account of our work on developing stereoselective cyclopropanations of furans and pyrroles as a facile entry into donor-acceptor substituted cyclopropanes. The application of these building blocks for the synthesis of paraconic acids, sesquiterpene lactones, pyrrolidinones, and conformationally restricted β-amino acids is discussed.

Die Trifluormethylchlorsulfonierung von Alkenen gelingt durch die Kombination von sichtbarem Licht und [Cu(dap)₂]Cl als Photoredoxkatalysator. Im Gegensatz dazu katalysieren [Ru(bpy)₃]Cl₂, [Ir(ppy)₂(dtbbpy)]PF₆ oder Eosin Y eine Trifluormethylchlorierung. [Cu(dap)₂]Cl spielt in diesem Prozess eine zweifache Rolle: Einerseits agiert es als Elektronentransferreagens, andererseits koordiniert es die Reagentien für die Bindungsbildung.

A visible-light-mediated procedure for the unprecedented trifluoromethylchlorosulfonylation of unactivated alkenes is presented. It uses [Cu(dap)₂]Cl as catalyst, and contrasts with [Ru(bpy)₃]Cl₂, [Ir(ppy)₂(dtbbpy)]PF₆, or eosin Y that exclusively give rise to trifluoromethylchlorination of the same alkenes. It is assumed that [Cu(dap)₂]Cl plays a dual role, that is, acting both as an electron transfer reagent as well as coordinating the reactants in the bond forming processes.

Palladium nanoparticles are deposited on the surface of highly magnetic carbon-coated cobalt nanoparticles. In contrast to the established synthesis of Pd nanoparticles via reduction of Pd(II) precursors, the microwave decomposition of a Pd(0) source leads to a more efficient Pd deposition, resulting in a material with considerably higher activity in the hydrogenation of alkenes. Systematic variation of the Pd loading on the carbon-coated cobalt nanoparticle surface reveals a distinct trend to higher activities with decreased loading of Pd. The activity of the catalyst is further improved by the addition of 10 vol% Et₂O to iso-propanol that is found to be the solvent of choice. With respect to activity (turnover frequencies up to 11 095 h⁻¹), handling, recyclability through magnetic decantation, and leaching of Pd (≤6 ppm/cycle), this novel magnetic hybrid material compares favorably to conventional Pd/C or Pd@CNT catalysts.

Light-induced electron transfer (Cu^I to Cu^II), oxidative addition (Cu^I to Cu^III), or the activation of copper alkene or alkyne complexes are possible key steps that offer unique possibilities for organic synthesis, including [2+2]-cycloadditions, cross-coupling reactions or atom transfer radical additions. This Minireview provides an overview on the photophysical properties of photocatalysts based on copper and on synthetic transformations mediated by them.

The enantioselective synthesis of cytostatic and antibiotic xanthatin (1 a) is reported. As a key intermediate, a bicyclic compound 2 was identified, which can be readily synthesized from methyl-2-furoic acid in diastereo- and enantiomerically pure form. Compound 2 can be functionalized regio- and stereoselectively at C-6 and C-7, allowing the facile introduction of the functionalities found in xanthatin, as well as the synthesis of derivatives thereof. Moreover, a robust strategy for the introduction of the exo-methylene group at C-3, commonly found in many sesquiterpenes, was developed that makes use of masking the alkene in the α,β-unsaturated carbonyl system by O-pivaoyl, which is stable under acidic and mild basic conditions but eliminated upon treatment with strong bases.

The Jørgensen–Hayashi catalyst [(S)-α,α-diphenylprolinol trimethylsilyl ether] was grafted onto the surface of two different supports: phosphorus dendrimers (generations 1 to 3) and magnetic, polymer-coated cobalt/carbon (Co/C) nanobeads. These new supported catalysts displayed high activities and selectivities in the Michael additions of a wide range of aldehydes to different nitroolefins. Moreover, the dendrimer of the third generation displayed excellent recycling abilities since it could be recovered and reused in 7 consecutive runs without loss of activity.

Magnetically recoverable and reusable CuFe₂O₄ nanoparticles are shown to be highly efficient catalysts for the one-pot synthesis of biologically important 1,4-diaryl-1,2,3-triazoles starting from boronic acids, sodium azide, and acetylenes. The use of aqueous reaction medium at room temperature, the low cost and facile recovery of the catalyst by application of an external magnetic field, and consistently high catalytic efficiency for at least three consecutive cycles renders the protocol operationally attractive.

Unprecedented magnetic borohydride exchange (mBER), magnetic Wang aldehyde (mWang) and magnetic amine resins were prepared from highly magnetic polymer-coated cobalt or iron nanoparticles. Microwave irradiation was used to obtain excellent degrees of functionalization (>95 %) and loadings (up to 3.0 mmol g⁻¹) in short reaction times of 15 min or less. A small library of ureas and thioureas was synthesized by the exclusive application of these magnetic resins. As a first step, a reductive amination of aromatic and aliphatic aldehydes was carried out with mBER. The excess of primary amine needed to complete the reaction was subsequently scavenged selectively by mWang. Simple magnetic decantation from the resins resulted in secondary amines in good to excellent yields and purities. The used magnetic resins were efficiently regenerated and reused for the next run. In a second step, the secondary amines were converted to trisubstituted (thio)ureas in excellent yields and purities by stirring with an excess of iso(thio)cyanate, which was scavenged by addition of the magnetic amine resin after completion of the reaction. The whole reaction sequence is carried out without any purification apart from magnetic decantation; moreover, conventional magnetic stirring can be used as opposed to the vortexing required for polystyrene resins.

An operationally simple method for the acylation of amines utilizing carbon-coated metal nanoparticles as recyclable supports is reported. Highly magnetic carbon-coated cobalt (Co/C) and iron (Fe/C) nanobeads were functionalized with a norbornene tag (Nb-tag) through a “click” reaction followed by surface activation employing Grubbs-II catalyst and subsequent grafting of acylated N-hydroxysuccinimide ROMPgels (ROMP=ring-opening metathesis polymerization). The high loading (up to 2.6 mmol g⁻¹) hybrid material was applied in the acylation of various primary and secondary amines. The products were isolated in high yields (86–99%) and excellent purities (all >95 % by NMR spectroscopy) after rapid magnetic decantation and simple evaporation of the solvents. The spent resins were successfully re-acylated by acid chlorides, anhydrides, and carboxylic acids and reused for up to five consecutive cycles without considerable loss of activity.

The facile synthesis of polyethylene glycol (PEG)-immobilized iron(II) porphyrin using a copper-catalyzed azide-alkyne [3+2] cycloaddition “click” reaction is reported. The prepared complex 5 (PEG-C₅₁H₃₉FeN₇O) was found to be an efficient catalyst for the selective olefination of aldehydes with ethyl diazoacetate in the presence of triphenylphosphine, and afforded excellent olefin yields with high (E) selectivities. The PEG-supported catalyst 5 was readily recovered by precipitation and filtration, and was recycled through ten runs without significant activity loss.

A new class of oxazoline ligands, named SupraBox, was studied. These ligands possess an additional urea functionality to generate supramolecular bidentate ligands in transition-metal complexes, by the establishment of hydrogen bonds between the urea N-hydrogens of one ligand and the carbonyl oxygen of a second one. A library of 16 SupraBox ligands was prepared using 5 differently substituted oxazoline nuclei, 4 linkers and 3 different urea substituents. The formation of copper(II) and palladium(II) complexes was investigated by MS, UV/Vis and ¹H-NMR spectroscopy. The SupraBox library was screened in the copper-catalyzed asymmetric benzoylation of vic-diols. Good selectivities were obtained in the kinetic resolution of racemic hydrobenzoin [up to 86 % ee and selectivity (s) = 28] and in the desymmetrization of meso-hydrobenzoin (up to 88 % ee).

Over the years, organic synthesis has witnessed several improvements through the development of new chemical transformations or more efficient reagents for known processes. Likewise, technological advances, aiming at speeding up reactions and facilitating their work-up, have established themselves in academic as well as in industrial laboratories. In this Minireview, we highlight very recent developments in flow chemistry, focusing on organometallic reagents and catalysts. First, we describe reactions with homogeneous catalysts immobilized on different support materials using the concept of packed bed reactors. In the last chapter, we will discuss applications that utilize organometallic reagents.

The CoCl₂/L-proline (1:2) system was found to be an excellent catalyst for direct aldol reactions. Excellent yields (up to 93 %) and a significant improvement in diastereoselectivity (anti/syn up to 45:1) as well as enantioselectivity (up to more than 99 % ee) compared with using proline as the sole catalyst were observed. This catalyst system was successfully applied to both cyclic and acyclic ketones in combination with aromatic and aliphatic aldehydes. In situ chelation of CoCl₂ and proline (1:2) is proposed to promote the reaction through a six-membered Zimmermann–Traxler type transition state involving the positioning of proline-enamine and the aldehyde through chelation to Co^II.

A novel hybrid material is reported as support for a recyclable palladium catalyst via surface immobilization of a ligand onto Co-based magnetic nanoparticles (NPs). A standard “click” reaction is utilized to covalently attach a norbornene tag (Nb-tag) to the surface of the carbon coated cobalt NPs. The hybrid magnetic nanoparticles are produced by initiating polymerization of a mixture containing both Nb-tagged ligand (Nb-tagged PPh₃) and Nb-tagged carbon coated cobalt NPs. In turn, the norbornene units are suitably functionalized to serve as ligands for metal catalysts. A composite material is thus obtained which furnishes a loading that is one order of magnitude higher than the value obtained previously for the synthesis of functionalized Co/C-nanopowders. This allows for its application as a hybrid support with high local catalyst concentrations, as demonstrated for the immobilization of a highly active and recyclable palladium complex for Suzuki-Miyaura cross-coupling reactions. Due to the explicit magnetic moment of the cobalt-NPs, the overall magnetization of this organic/inorganic framework is significantly higher than of polymer coated iron oxide nanoparticles with comparable metal content, hence, its rapid separation from the reaction mixture and recycling via an external magnetic field is not hampered by the functionalized polymer shell.

The palladium-catalyzed aerobic oxidation of alkenes and especially styrenes (Wacker oxidation) by using chiral pseudo C₂-symmetrical bis(isonitrile) ligands in the absence of further cocatalysts gives rise to methyl ketones in a highly chemoselective manner. The palladium bis(isonitrile) catalyst was characterized by NMR spectroscopy and X-ray structure analysis, revealing a dissymmetric coordination of palladium by the two isonitrile moieties.

Die aerobe Palladium-katalysierte Oxidation von Alkenen zu Methylketonen (Wacker Oxidation), insbesondere von Styrolen, gelingt mit chiralen Pseudo-C₂-symmetrischen Bisisonitrilliganden ohne weitere Cokatalysatoren mit hoher Chemoselektivität. Strukturelle Untersuchungen der Katalysatoren mittels NMR und Röntgenstrukturanalyse ergab, dass sowohl in Lösung wie auch im Festkörper Palladium unsymmetrisch durch die zwei Isonitrileinheiten koordiniert wird.

Two different types of azide functionalized magnetite@silica nanoparticles are synthesized, which are ideally suited as inexpensive supports for catalysts and reagents as demonstrated with the grafting of copper(II)-azabis(oxazoline) complexes via a copper(I) catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The potential of the immobilized complexes as catalysts is tested in the desymmetrization of racemic 1,2-diols through asymmetric benzoylation. Compared to azabis(oxazolines) “clicked” to common polymeric supports such as MeOPEG or Merrifield resin, Fe₃O₄@SiO₂ proves to be superior with respect to activity and selectivity, as exemplified by employing the catalysts in up to five runs with consistent high activity and selectivity. Recycling of the catalysts is achieved quantitatively by magnetic decantation.

New fluorous-tagged azabis(oxazoline) ligands were prepared using the copper-catalyzed azide-alkyne cycloaddition as ligation method. The resulting ligands were tested in copper-catalyzed asymmetric benzoylations (up to 99% ee), nitroaldol (up to 90% ee), and Michael reactions (up to 82% ee). The combination of unpolar fluorinated alkyl chains and polar triazole moieties imposes properties that are beneficial for the catalysts with respect to recyclability and selectivity. The scope and limitation of this strategy in comparison to analogous catalysts immobilized on methoxypolyethylene glycol (MeOPEG) or polystyrene is discussed. Moreover, this study shows that the choice of solvent for a given reaction is crucial to arrive at highly recyclable bis(oxazoline) catalysts.

Simple monosulfonated cyclohexane-1,2-diamines are highly enantioselective organocatalysts for the conjugate addition of ketones to nitro olefins. By focusing on aromatic ketones as the most challenging substrates, selectivities of up to 98 % ee can be achieved for the title reaction. Moreover, a three-component process between the primary amine catalyst, the nitroalkene, and the ketone, which results in the irreversible formation of pyrrols has been recognized as a reaction pathway for catalyst deactivation.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The biosynthetic pathways of sesquiterpene lactones are described in conjunction with recent developments in the total syntheses of various biologically active guaianolides. Different strategies towards the 5,7,5-membered ring system are highlighted. Oxidative diol cleavages, aldol reactions, and intramolecular cyclopropanations were used as key reactions to construct the racemic guaianolide core system. Radical cyclizations, as well as ring closing metathesis, were successfully applied in asymmetric approaches. Biomimetic reactions were also applied as versatile tools for the construction of these highly complex natural products.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Simple bis(oxazoline) ligands, especially azabis(oxazolines), can promote the copper(II)-catalyzed Michael addition of indoles to benzylidene malonates with up to >99 % ee (ee=enantiomeric excess), provided that the ligand/metal ratio is tuned meticulously with particular regard to the electronic properties of the substrate. Despite a common paradigm followed in many asymmetric catalyses, an excess of chiral ligand is not always beneficial. In fact any excess of ligand has to be avoided to reach excellent enantioselectivities when electron-rich benzylidene malonates are used. On the contrary, malonates carrying an electron-withdrawing group require an excess of ligand for an optimum ee value. A correlation of optical yields versus the σ_I values of several para substituents shows a sigmoid trajectory. In the presence of an additive, such as triflate, the significance of the ligand/metal ratio vanishes and very good enantioselectivities are achieved at any rate—no matter whether electron-donating or withdrawing substituents are present.

The copper-catalyzed [3+2] azide–alkyne cycloaddition and the Staudinger ligation are readily applicable and highly efficient for the immobilization of cobalt Schiff base complexes onto polystyrene resins. Stepwise synthesis of polymer-bound Schiff bases followed by their subsequent complexation with metal ions were successfully carried out. Direct covalent attachment of preformed homogeneous cobalt Schiff base complexes to the resins was also possible. The catalytic efficiency of the so-prepared polystyrene-bound cobalt Schiff bases was studied for the oxidation of alcohols to carbonyl compounds using molecular oxygen as oxidant. The immobilized complexes were highly efficient and even more reactive than the corresponding homogenous analogues, thus affording better yields of oxidized products within shorter reaction times. The supported catalysts could easily be recovered from the reaction mixture by simple filtration and reused for subsequent experiments with consistent catalytic activity.