Choosing between Ti(II) and Ti(III): selective reduction of titanocene dichloride by elemental lanthanides.

The reduction of titanocene dichloride Cp2TiCl2 with lanthanide metals has led to the discovery of a surprising lanthanide effect: while with most lanthanides, a divalent [Cp2Ti] equivalent was obtained, the use of samarium or ytterbium only led to the reduction to trivalent [Cp2TiCl]-type complexes, including the structurally characterized heterobimetallic complex [Cp2Ti(µ-Cl)2SmCl2(THF)3]. These results were corroborated by reactivity studies (alkyne coupling and radical reactions), EPR spectroscopy and electrospray mass spectrometry, providing new insights into the reduction chemistry of lanthanide metals.

Visible-light Organic Photosensitizers Based on 2-(2-Aminophenyl)benzothiazoles for Photocycloaddition Reactions.

We have studied 2-(2-aminophenyl)benzothiazole and related derivatives for their photophysical properties in view of employing them as new and readily tunable organic photocatalysts. Their triplet energies were estimated by DFT calculations to be in the range of 52-57 kcal·mol-1 suggesting their suitability for the [2+2] photocycloaddition of unsaturated acyl imidazoles with styrene derivatives. Experimental studies have shown that 2­(2­aminophenyl)benzothiazoles comprising alkylamino groups (NHMe, NHiPr) or the native amino group provide the best photocatalytic results in these visible-light mediated [2+2] reactions without the need of any additives yielding a range of cyclobutane derivatives. A combined experimental and theoretical approach has provided insights into the underlying triplet-triplet energy transfer process.

Metal-Free Decarboxylative Allylation of Oxime Esters under Light Irradiation.

Allylation reactions, often used as a key step for constructing complex molecules and drug candidates, typically rely on transition-metal (TM) catalysts. Even though TM-free radical allylations have been developed using allyl-stannanes, -sulfides, -silanes or -sulfones, much less procedures have been reported using simple and commercially available allyl halides, that are used for the preparation of the before-mentioned allyl derivatives. Here, we present a straightforward photocatalytic protocol for the decarboxylative allylation of oxime esters using allyl bromide derivatives under metal-free and mild conditions. This methodology yields a diverse variety of functionalized molecules including several pharmaceutically relevant molecules.

Activation of glycosyl methylpropiolates by TfOH.

Activation of glycosyl methylpropiolates by TfOH was investigated. Armed and superarmed glycosyl donors can be activated by use of 0.2 equivalent TfOH whereas 1.0 equivalent of TfOH was required for the activation of the disarmed glycosyl donors. All the glycosidations gave very good yields. The method is suitable for synthesis of glycosides and disaccharides and it may result in the hydrolysis of the interglycosidic bond if the sugar at the non-reducing end is armed or superarmed. These problems are not seen when gold-catalyzed activation procedures are invoked for the activation of glycosyl alkynoates.

Rare Earths-The Answer to Everything.

Rare earths, scandium, yttrium, and the fifteen lanthanoids from lanthanum to lutetium, are classified as critical metals because of their ubiquity in daily life. They are present in magnets in cars, especially electric cars; green electricity generating systems and computers; in steel manufacturing; in glass and light emission materials especially for safety lighting and lasers; in exhaust emission catalysts and supports; catalysts in artificial rubber production; in agriculture and animal husbandry; in health and especially cancer diagnosis and treatment; and in a variety of materials and electronic products essential to modern living. They have the potential to replace toxic chromates for corrosion inhibition, in magnetic refrigeration, a variety of new materials, and their role in agriculture may expand. This review examines their role in sustainability, the environment, recycling, corrosion inhibition, crop production, animal feedstocks, catalysis, health, and materials, as well as considering future uses.

Photocatalyzed Amination of Alkyl Halides to Access Primary Amines.

We demonstrate that oxime ester derivatives can be used as both a halogen atom transfer (XAT) agent and an imine source under photocatalytic conditions, allowing the radical amination of alkyl halides, resulting in the formation of a broad scope of imines. Hydrolysis of the latter gives direct access to the corresponding primary amines. Mechanistically, the reaction is believed to proceed through the formation of aryl radical intermediates, which are responsible for the activation of alkyl halides via XAT.

Divalent ansa-Octaphenyllanthanocenes: Synthesis, Structures, and EuII Luminescence.

Reductive dimerization of fulvenes using low-valent metal precursors is a straightforward one-step approach to access ethylene-bridged metallocenes. This process has so far mainly been employed with fulvenes carrying one or two substituents in the exocyclic position. In this work, a new synthesis of the unsubstituted exocyclic 1,2,3,4-tetraphenylfulvene (1), its full structural characterization by NMR spectroscopy and single-crystal X-ray diffraction, as well as some photophysical properties and its first use in reductive dimerization are described. This fulvene reacted with different lanthanoid metals in thf to provide the divalent ansa-octaphenylmetallocenes [Ln(C5Ph4CH2)2(thf)n] (Ln = Sm, n = 2 (2); Ln = Eu, n = 2 (3); and Ln = Yb, n = 1 (4)). These complexes were characterized by X-ray diffraction, laser desorption/ionization time of flight mass spectrometry, and, in the case of Sm and Yb, multinuclear NMR spectroscopy, showing the influence of the ansa-bridge on solution and solid-state structures compared to previously reported unbridged metallocenes. Furthermore, the luminescence properties of the Eu ansa complex 3 were studied in solution and the solid state, revealing significant differences with the known octa- and deca-phenyleuropocenes, [Eu(C5Ph4H)2(dme)] and [Eu(C5Ph5)2].

Copper-Catalyzed Regio- and Stereoselective Hydrothiolation of Allenamides, Enamides, and Ynamides.

We report a simple protocol for the copper-catalyzed hydrothiolation of N-unsaturated precursors, i.e., allenamides, enamides, and ynamides, under mild conditions. This method proceeds with a low loading of a commercially available Cu(CH3CN)4PF6 catalyst and enables the room-temperature transformation of a wide range of aromatic and aliphatic thiols into allylic or vinylic thioethers, 1,3-dithioethers, and thioaminals with good regio- and stereoselectivity.

Photo-Induced Halogen-Atom Transfer: Generation of Halide Radicals for Selective Hydrohalogenation Reactions.

The first photo-mediated process enabling the generation of halide radicals by Halogen-Atom Transfer (XAT) is described. Contrary to radical transformations involving XAT reactivity, which exploit stable carbon radicals, this unique approach uses 1,2-dihaloethanes for the generation of unstable carbon radicals by XAT. These transient radicals then undergo ß-scission with release of ethylene and formation of more stable halide radicals which have been used in selective hydrohalogenations of a large number of unsaturated hydrocarbons, including Michael acceptors, unactivated alkenes and alkynes. This hydrohalogenation is tolerant of a broad range of functionalities and is believed to proceed through a radical-chain manifold that propagates by the use of silane derivatives.

Selective carbon-phosphorus bond cleavage: expanding the toolbox for accessing bulky divalent lanthanoid sandwich complexes.

The synthesis of two new tetra- and penta-phenycyclopentadienyldiphenylphosphine pro-ligands which readily undergo selective C-P bond cleavage has allowed for the facile synthesis of bulky divalent octa- and deca-phenylmetallocenes of europium, ytterbium and samarium.

Tuning the Regioselective Functionalization of Trifluoromethylated Dienes via Lanthanum-Mediated Single C-F Bond Activation.

The development of new fluorine-containing building blocks and their efficient synthetic access is currently a challenging research field. Herein, the highly regio- and stereoselective addition of a large range of aldehydes onto trifluoromethylated benzofulvenes was achieved using a simple La/I2 /DIBAL-Cl system via a selective C-F bond activation process. This versatile methodology provided homodienyl alcohols bearing a terminal CF2 -alkene with potential further applications, as shown by the dehydration to the first benzofulvenes carrying a difluorovinyl group. In addition, for certain electron-poor aldehydes, unprecedented ipso substitution of the CF3 group in a diene was observed, which, according to DFT studies, is related to the presence of the large, Lewis-acidic lanthanum metal.

Diastereoselective Synthesis of Axially Chiral Xylose-Derived 1,3-Disubstituted Alkoxyallenes: Scope, Structure, and Mechanism.

The deprotonation of differently substituted propargyl xylosides with s-BuLi/TMEDA followed by protonation with t-butanol at -115 °C provided a range of new axially chiral 1,3-disubstituted alkoxyallenes in a diastereoselective way. Numerous reaction parameters such as solvent, temperature, or protonating agent were examined as well as protecting groups on the xyloside moiety and the influence of the substituents on the alkyne part. The configuration of the main diastereoisomer of 3-methyl-1-xyloside-allene was determined for the first time by single-crystal X-ray diffraction analysis and nOe NMR experiments. Furthermore, DFT calculations on the propargyl/allenyl lithium intermediates formed in the course of the deprotonation reaction provided new structural insights of these complexes. The subsequent protonation process with alcohols was investigated by theoretical surface exploration, revealing the importance of the approach of the alcohol toward the lithium compounds on the reaction outcome.

Aerobic and Ligand-Free Manganese-Catalyzed Homocoupling of Arenes or Aryl Halides via in Situ Formation of Aryllithiums.

Ligand-free manganese-catalyzed homocoupling of arenes or aryl halides can be carried out under aerobic conditions via the in situ formation of the corresponding aryllithiums. A wide range of biaryls and derivatives has been obtained, and a mechanism involving monomeric manganese-oxo complexes has been proposed on the basis of DFT calculations.

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes.

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the possibility of accessing unique fluorine-containing molecules, which are difficult to obtain by other synthetic pathways. Among various metals, which can undergo C-F activation, lanthanides (Ln) are good candidates as they form strong Ln-F bonds. Lanthanide metals are strong reducing agents with a redox potential Ln3+/Ln of approximately -2.3 V, which is comparable to the value of the Mg2+/Mg redox couple. In addition, lanthanide metals display a promising functional group tolerance and their reactivity can vary along the lanthanide series, making them suitable reagents for fine-tuning reaction conditions in organic and organometallic transformations. However, due to their oxophilicity, lanthanides react readily with oxygen and water and therefore require special conditions for storage, handling, preparation, and activation. These factors have limited a more widespread use in organic synthesis. We herein present how dysprosium metal - and by analogy all lanthanide metals - can be freshly prepared under anhydrous conditions using glovebox and Schlenk techniques. The freshly filed metal, in combination with aluminum chloride, initiates the selective C-F activation in trifluoromethylated benzofulvenes. The resulting reaction intermediates react with nitroalkenes to obtain a new family of difluoroalkenes.

Picking One out of Three: Selective Single C-F Activation in Trifluoromethyl Groups.

The introduction of a trifluoromethyl (CF3 ) group into an organic molecule can modify its chemical behavior and lead to changes in its physicochemical and pharmacological properties. The CF3 group is often chosen for its chemical inertness and stability, which are related to the strong C-F bonds. In recent years, the potential of gaining straightforward access to difluorinated compounds through selective single C-F activation in CF3 groups has been unveiled. This review describes the latest methodologies for the synthesis of difluoromethylated arenes, difluoroalkenes and difluorinated aldol products of potential synthetic and/or biological interest, employing low-valent metals, transition metal catalysis, FLP and Lewis acid mediated transformations as well as photoredox catalysis.

Single or Synergistic Kinetic Resolutions of Chiral Allylalanes: Two Complementary Routes for the Asymmetric Synthesis of Syn Homoallylamines.

Two strategies based on kinetic resolution(s) of chiral alanes and providing enantioenriched syn homoallylamines are reported. The first implies a single kinetic resolution of the alane using camphor; the second requires two sequential kinetic resolutions using the synergistic combination of (-)-camphor/(R)-tert-butylsulfinamide-derived imines. This syn selectivity, specific to the use of allyaluminum, opens the way to the preparation of valuable building blocks as illustrated by the synthesis of (+)-epilupinamine.

Generation of ϵ,ϵ-Difluorinated Metal-Pentadienyl Species through Lanthanide-Mediated C-F Activation.

Heavy metal on Lewis acid: The combination of lanthanide metals and AlCl3 has been employed for selective single C-F activation in benzofulvenes comprising an exocyclic CF3 substituent. Intermediate ϵ,ϵ-difluorinated metal-dienyl species react with a large variety of aldehydes in a highly regio- and diastereoselective fashion to afford 1,1-disubstituted indenes bearing a difluorovinyl group. These new building blocks have been further transformed through a hydrogenation-cyclization process into fluorinated heterocyclic spiro compounds.

Recent Advances in the Chemistry of Pentafulvenes.

Pentafulvenes are a unique class of compounds that originally attracted attention due to their propensity to display nonbenzenoid aromaticity. Subsequently, they were recognized as valuable synthons for the construction of a wide range of compounds by virtue of their ability to display multiple cycloaddition profiles. Naturally, this area of organic chemistry has experienced rapid growth over the last five decades, fueled by elegant work showcasing the unique reactivity of pentafulvenes in a plethora of cycloaddition reactions. In this Review, we have attempted to provide a systematic account of the methods for the generation of pentafulvenes, their rich and varied cycloaddition chemistry, organometallic reactions, and theoretical studies that support their versatility. Further, we have highlighted their applications in the synthesis of a variety of complex structural frameworks. It is our conviction that this Review will be useful to a wide range of chemists, and will spur further research in this promising area.

(+)-Camphor-mediated kinetic resolution of allylalanes: a strategy towards enantio-enriched cyclohex-2-en-1-ylalane.

An efficient (+)-camphor-mediated kinetic resolution of racemic cyclohex-2-en-1-ylalane is described. This approach provides an enantiomerically enriched form of the alane, in situ available for synthetic uses. Applied to the allylation of aldehydes, this protocol leads to the corresponding homoallylalcohols in a highly enantioselective manner.

Lewis Acid Catalyzed Regioselective Hydroheteroarylation of Pentafulvenes.

A diverse approach toward the catalytic regioselective nucleophilic addition of nitrogen heterocycles to Lewis acid activated pentafulvenes has been established. The developed protocol introduces pentafulvenes as nonsymmetrical alkenes for the hydroheteroarylation reaction, providing alkylidenecyclopentenylation at the C-3 position of indoles and the C-2 position of pyrrole.