Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

The activation of carbon–fluorine (C?F) bonds is an important topic in synthetic organic chemistry. Metal‐mediated and ‐catalyzed elimination of β‐ or α‐fluorine proceeds under milder conditions than oxidative addition to C?F bonds. The β‐ or α‐fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations through these elimination processes (C?F bond cleavage), which are typically preceded by carbon–carbon (or carbon–heteroatom) bond formation, have been increasingly developed in the past five years as C?F bond activation methods. In this Minireview, we summarize the applications of transition‐metal‐mediated and ‐catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective with early studies and from a systematic perspective with recent studies.     

Organometallic Diaza‐dimetalla‐Norbornanes and ‐Cyclohexanes of Aluminium,Gallium and Indium

Selective formation of 1,3,3,4,6,6‐hexamethyl‐1,4‐diaza‐3,6‐diinda‐norborane was achieved by the reaction of bis(lithiomethyl‐methylamino)methane with dimethylindium chloride by simultaneous formation of two dative metal‐carbon and two metal‐nitrogen bonds accompanied by two ring closures. The synthesis of heterometallic compounds of this type, namely 1,3,3,4,6,6‐hexamethyl‐3‐alumina‐1,4‐diaza‐6‐galla‐norborane [Me₂AlCH₂N(Me)]CH₂[N(Me)CH₂GaMe₂], was also attempted by the reaction of bis(lithiomethyl‐methylamino)methane with dimethylaluminium and ‐gallium chloride. This compound is formed, but cannot be separated from the simultaneously formed homometallic compounds [Me₂MCH₂N(Me)]₂CH₂(M = Al, Ga). The compounds were identified by elemental analyses, mass spectra, NMR spectroscopy (¹H, ¹³C), and by determination of their crystal structures in which they are present as monomers. The norbornane‐like structure is favoured over potential isomers containing three‐membered rings and over polymeric aggregation in both compounds. In addition, the crystal structure of dimethyl(dimethylaminomethyl)indium was determined by single crystal X‐ray diffraction, which shows an intermolecular aggregation into a six‐membered ring dimer.     

Insertion of Isolated Alkynes into Carbon–Carbon σ‐Bonds of Unstrained Cyclic β‐Ketoesters via Transition‐Metal‐Free Tandem Reactions: Synthesis of Medium‐Sized Ring Compounds

The transition‐metal‐free insertion of isolated alkynes into carbon–carbon σ‐bonds of unstrained cyclic β‐dicarbonyl compounds has been reported. These tandem reactions offer an efficient synthesis of medium‐sized ring or fused‐ring compounds through ring expansion. The methodology has the potential to be widely used throughout organic synthesis due to the easily accessible starting materials and mild reaction conditions.     

Applications of Transition‐Metal‐Catalyzed Asymmetric Allylic Substitution in Total Synthesis of Natural Products: An Update

Metal‐catalyzed asymmetric allylic substitution (AAS) reaction is one of the most synthetically useful reactions catalyzed by metal complexes for the formation of carbon‐carbon and carbon‐heteroatom bonds. It comprises the substitution of allylic substrates with a wide range of nucleophiles or S_N2′‐type allylic substitution, which results in the formation of the above‐mentioned bonds with high levels of enantioselective induction. AAS reaction tolerates a broad range of functional groups, thus has been successfully applied in the asymmetric synthesis of a wide range of optically pure compounds. This reaction has been extensively used in the total synthesis of several complex molecules, especially natural products. In this review, we try to highlight the applications of metal (Pd, Ir, Mo, or Cu)‐catalyzed AAS reaction in the total synthesis of the biologically active natural products, as a key step, updating the subject from 2003 till date.     

Aromatic Chemistry in the Excited State: Facilitating Metal‐Free Substitutions and Cross‐Couplings

Transition‐metal‐catalyzed cross‐couplings between aromatic electrophiles and nucleophiles have revolutionized modern chemical syntheses. Nevertheless, transition‐metal‐free approaches are preferable, considering the various issues caused by metal catalysts. This Minireview summarizes the recent progress in the light‐enabled transition‐metal‐free formation of carbon–carbon and carbon–heteroatom bonds in aromatics, which opens a new avenue in aromatic reactions. From the mechanistic perspective, it classifies different reaction types of aryl electrophiles in an excited state with various nucleophiles. We believe this will provide more rationales for metal‐free aromatic substitutions and cross‐couplings with light, and guide the development of novel transformations of aromatic compounds facilitated by light.     

2,3,4,5‐Tetraethylpentela‐cyclo‐pentadienide (2,3,4,5‐Tetraethylpentolide) der Erdalkalimetalle Magnesium,Calcium, Strontium und Barium

2,3,4,5‐Tetraethylpentela‐cyclo‐pentadienides (2,3,4,5‐Tetraethylpentolides) of the Alkaline Earth Metals Magnesium, Calcium, Strontium, and Barium The reaction of bis(cyclopentadienyl)‐1‐zircona‐2,3,4,5‐tetraethyl‐cyclo‐penta‐2,4‐diene with ECl₃ (E = P, As, Sb) yields 1‐chloro‐tetraethylphosphole ( 1 ), ‐arsole ( 2 ) und ‐stibole ( 3 ). The reduction of these pentoles gives in a first step the corresponding octaethyldiphospholyle ( 4 ), ‐diarsolyle ( 5 ) and ‐distibolyle ( 6 ). Further reduction of these dipentolyles with magnesium and calcium leads in the presence of the corresponding dihalides to the formation of magnesium chlorid (2,3,4,5‐tetraethylphospholide) ( 7 ), ‐arsolide) ( 8 ) and ‐stibolide) ( 9 ) and calcium chlorid (2,3,4,5‐tetraethylphospholide) ( 10 ), ‐arsolide) ( 11 ) and ‐stibolide) ( 12 ), respectively. In the absence of alkaline earth metal dihalides no reaction is observed. For the larger metals strontium and barium the reduction of the dipentolyles succeeds in THF also without the addition of halides and the 1,1′‐dipentela‐octaethylstrontocene [E = P ( 13 ), As ( 14 ), Sb ( 15 )] as well as ‐barocene [E = P ( 16 ), As ( 17 ), Sb ( 18 )] are isolated halogen‐free. The strontocene crystallizes as a THF adduct whereas the barocene precipitates coligand‐free but with a chain structure. The molecular structures of 7 , 10 , and 16 are discussed.     

On‐Surface Synthesis of Cumulene‐Containing Polymers via Two‐Step Dehalogenative Homocoupling of Dibromomethylene‐Functionalized Tribenzoazulene

Cumulene compounds are notoriously difficult to prepare and study because their reactivity increases dramatically with the increasing number of consecutive double bonds. In this respect, the emerging field of on‐surface synthesis provides exceptional opportunities because it relies on reactions on clean metal substrates under well‐controlled ultrahigh‐vacuum conditions. Here we report the on‐surface synthesis of a polymer linked by cumulene‐like bonds on a Au(111) surface via sequential thermally activated dehalogenative C?C coupling of a tribenzoazulene precursor equipped with two dibromomethylene groups. The structure and electronic properties of the resulting polymer with cumulene‐like pentagon–pentagon and heptagon–heptagon connections have been investigated by means of scanning probe microscopy and spectroscopy methods and X‐ray photoelectron spectroscopy, complemented by density functional theory calculations. Our results provide perspectives for the on‐surface synthesis of cumulene‐containing compounds, as well as protocols relevant to the stepwise fabrication of carbon–carbon bonds on surfaces.     

Hypervalent‐Iodine‐Mediated Carbon–Carbon Bond Cleavage and Dearomatization of 9H‐Fluoren‐9‐ols

A transition‐metal‐free synthesis of spiro compounds from 9H‐fluoren‐9‐ols mediated by hypervalent iodine is reported. In this reaction, an unprecedented β‐carbon elimination of tertiary alkoxyliodine(III) to form new diaryliodonium salts is proposed. The obtained phenol intermediates undergo oxidative dearomatization to furnish a class of oxo‐spiro compounds. This domino reaction significantly increases the complexity of these molecules and shows excellent regio‐ and stereoselectivity.     

Cross‐Coupling of α‐Carbonyl Sulfoxonium Ylides with C−H Bonds

The functionalization of carbon–hydrogen bonds in non‐nucleophilic substrates using α‐carbonyl sulfoxonium ylides has not been so far investigated, despite the potential safety advantages that such reagents would provide over either diazo compounds or their in situ precursors. Described herein are the cross‐coupling reactions of sulfoxonium ylides with C(sp²)−H bonds of arenes and heteroarenes in the presence of a rhodium catalyst. The reaction proceeds by a succession of C−H activation, migratory insertion of the ylide into the carbon–metal bond, and protodemetalation, the last step being turnover‐limiting. The method is applied to the synthesis of benz[c]acridines when allied to an iridium‐catalyzed dehydrative cyclization.     

Organometall‐Reaktionen in Wasser

Water has attracted significant attention as an alternative solvent for organometallic reactions because it is nontoxic, nonflammable, and inexpensive, and is easily separated from organic products. Organometallic reactions, like the palladium‐catalyzed couplings of organic halides with organoboron compounds (Suzuki) and organotin reagents (Stille), are among the most widely used reactions for the formation of carbon‐carbon bonds. Owing to the discovery of water‐soluble, sulfonated phosphane derivatives and particularly the design of water‐soluble palladium‐catalysts it was possible to import these reactions into aqueous media. Another efficient, metal‐catalyzed, carbon‐carbon bond‐forming process that is nowadays possible in aqueous media is the olefin metathesis. The approaches so far include the use of water‐soluble ruthenium‐catalysts, surfactants and additives, ultrasonication, the introduction of polar quaternary ammonium groups or the incorporation of PEG as a water solubilizing moiety. The last point bears also a great potential for further developments in the removal of ruthenium‐containing byproducts. Additionally, water is the ideal reaction environment for polar, water soluble substrates such as natural product or pharmaceuticals.     

Bis‐NHC Chelate Complexes of Nickel(0) and Platinum(0)

For a long time d¹⁰‐ML₂ fragments have been known for their potential to activate unreactive bonds by oxidative addition. In the development of more active species, two approaches have proven successful: the use of strong σ‐donating ligands leading to electron‐rich metal centers and the employment of chelating ligands resulting in a bent coordination geometry. Combining these two strategies, we synthesized bis‐NHC chelate complexes of nickel(0) and platinum(0). Bis(1,5‐cyclooctadiene)nickel(0) and ‐platinum(0) react with bisimidazolium salts, deprotonated in situ at room temperature, to yield tetrahedral or trigonal‐planar bis‐NHC chelate olefin complexes. The synthesis and characterization of these complexes as well as a first example of C? C bond activation with these systems are reported. Due to the enforced cis arrangement of two NHCs, these compounds should open interesting perspectives for bond‐activation chemistry and catalysis.     

Enzyme‐Responsive Intracellular‐Controlled Release Using Silica Mesoporous Nanoparticles Capped with ε‐Poly‐L‐lysine

The synthesis and characterization of two new capped silica mesoporous nanoparticles for controlled delivery purposes are described. Capped hybrid systems consist of MCM‐41 nanoparticles functionalized on the outer surface with polymer ε‐poly‐L ‐lysine by two different anchoring strategies. In both cases, nanoparticles were loaded with model dye molecule [Ru(bipy)₃]²⁺. An anchoring strategy involved the random formation of urea bonds by the treatment of propyl isocyanate‐functionalized MCM‐41 nanoparticles with the lysine amino groups located on the ε‐poly‐L ‐lysine backbone (solid Ru‐rLys‐S1 ). The second strategy involved a specific attachment through the carboxyl terminus of the polypeptide with azidopropyl‐functionalized MCM‐41 nanoparticles (solid Ru‐tLys‐S1 ). Once synthesized, both nanoparticles showed a nearly zero cargo release in water due to the coverage of the nanoparticle surface by polymer ε‐poly‐L ‐lysine. In contrast, a remarkable payload delivery was observed in the presence of proteases due to the hydrolysis of the polymer’s amide bonds. Once chemically characterized, studies of the viability and the lysosomal enzyme‐controlled release of the dye in intracellular media were carried out. Finally, the possibility of using these materials as drug‐delivery systems was tested by preparing the corresponding ε‐poly‐L ‐lysine capped mesoporous silica nanoparticles loaded with cytotoxic drug camptothecin (CPT), CPT‐rLys‐S1 and CPT‐tLys‐S1 . Cellular uptake and cell‐death induction were studied. The efficiency of both nanoparticles as new potential platforms for cancer treatment was demonstrated.     

Fully Conjugated Two‐Dimensional sp2‐Carbon Covalent Organic Frameworks as Artificial Photosystem I with High Efficiency

The synthesis of fully conjugated sp²‐carbon covalent organic frameworks (COF) is extremely challenging given the difficulty of the formation of very stable carbon‐carbon double bonds (‐C=C‐). Here, we report the successful preparation of a 2D COF (TP‐COF) based on triazine as central planar units bridged by sp²‐carbon linkers through the ‐C=C‐ condensation reaction. High‐resolution‐transmission electron microscopy (HRTEM) clearly confirmed the tessellated hexagonal pore structure with a pore center‐to‐center distance of 2 nm. Powder X‐ray diffraction (PXRD) together with structural simulations revealed an AA stacking mode of the obtained layered structure. TP‐COF turned out to be an excellent semiconductor material with a LUMO energy of ?3.23 eV and a band gap of 2.36 eV. Excitingly, this novel sp²‐carbon conjugated TP‐COF exhibited unprecedented coenzyme regeneration efficiency and can significantly boost the coenzyme‐assisted synthesis of l ‐glutamate to a record‐breaking 97 % yield within 12 minutes.     

Silver(I)‐Catalyzed Tandem 1,3‐Acyloxy Migration/Mannich‐type Addition/Elimination of the Sulfonyl Group of N‐Sulfonylhydrazone‐propargylic Esters to 5,6‐Dihydropyridazin‐4‐one Derivatives

The addition of nucleophiles to C?N bonds offers a highly efficient synthetic strategy for accessing nitrogen‐containing molecules. 1 Among the well‐developed addition reactions, such as the highly efficient Mannich reaction, various C? H bond‐activated compounds including carboxylic acid derivatives, nitroalkanes, and terminal alkynes have been applied as nucleophiles to achieve different classes of amines. 2 However, employing new nucleophiles without activated C? H bonds, such as internal alkynes and allenic esters are limited when using metal catalysts. 3 Herein, we wish to report a new addition of allenic esters to C?N bonds initiated by a silver‐catalyzed 1,3‐migration of propargylic esters.     

From Supramolecular Species to Self‐Templated Porous Carbon and Metal‐Doped Carbon for Oxygen Reduction Reaction Catalysts

The preparation of carbon materials usually involves the decomposition of precursors and the reorganization of the as‐generated fragments. However, the cleavage of bonds and the simultaneous formation of new bonds at nearly the same positions prevents effective yet precise fabrication. Herein, a supramolecular precursor, cucurbit[6]uril, that contains multiple bonds with distinct bond strengths is proposed to decouple the twin problem of simultaneous bond cleavage and formation, allowing multistage transformations to hierarchical porous carbon and metal‐doped carbon in a single yet effective pyrolysis step without the need of a template or additional purification. As a proof‐of‐concept, the Fe‐doped carbon electrocatalysts realized a Pt/C‐like half‐wave potential of 0.869 V vs. RHE and small Tafel slope of 51.3 mV dec^?1 in oxygen reduction reaction.     

ortho‐(Aminomethyl)phenylboronic acids—synthesis,structure and sugar receptor activity

A series of ortho‐(aminomethyl)phenylboronic acids was synthesized and their structures were determined by single‐crystal X‐ray diffraction. The structures are stabilized by the inter‐ and intramolecular hydrogen bonds. The sugar‐binding ability of these compounds was evaluated for D ‐glucose, D ‐fructose and D ‐galactose by the competition assay with Alizarin Red S (ARS). The results indicate that the sugar binding ability and selectivity towards sugars depend on the substituents in amino group. Copyright © 2008 John Wiley & Sons, Ltd.     

Iridium‐Catalyzed Synthesis of Diaryl Ethers by Means of Chemoselective CF Bond Activation and the Formation of BF Bonds

Transition‐metal‐catalyzed C? F activation, in comparison with C? H activation, is more difficult to achieve and therefore less fully understood, mainly because carbon–fluorine bonds are the strongest known single bonds to carbon and have been very difficult to cleave. Transition‐metal complexes are often more effective at cleaving stronger bonds, such as C(sp²)? X versus C(sp³)? X. Here, the iridium‐catalyzed C? F activation of fluorarenes was achieved through the use of bis(pinacolato)diboron with the formation of the B? F bond and self‐coupling. This strategy provides a convenient method with which to convert fluoride aromatic compounds into symmetrical diaryl ether compounds. Moreover, the chemoselective products of the C? F bond cleavage were obtained at high yields with the C? Br and C? Cl bonds remaining.     

Synthesis of Long,Palladium End‐Capped Polyynes through the Use of Asymmetric 1‐Iodopolyynes

The synthesis of a unique series of long, asymmetric 1‐iodopolyynes ( 1 ‐C_nI and 2 ‐C_nI) with the sp‐hybridized carbon chain up to a decapentayne is reported. These compounds were then used as substrates in reactions with Pd(PPh₃)₄ leading to another series of palladium end‐capped polyynes, which were unstable in solution. Organometallic octatetraynes 1 ‐C₈[Pd]I, 2 ‐C₈[Pd]I, and decapentayne 1 ‐C₁₀[Pd]I are palladium end‐capped polyyne compounds with the longest carbon chains reported so far. All the complexes as well as their organic precursors were fully characterized by NMR, HRMS(ESI), IR, TGA‐DTA, and UV/Vis techniques, and the X‐ray crystal structures of two silyl‐protected precursors and one palladium complex are presented. The synthetic approach for palladium species is envisioned as a general route for the synthesis of labile organometallic polyynes.     

d–d Dative Bonding Between Iron and the Alkaline‐Earth Metals Calcium,Strontium, and Barium

Double deprotonation of the diamine 1,1′‐(tBuCH₂NH)‐ferrocene ( 1 ‐H₂) by alkaline‐earth (Ae) or Eu^II metal reagents gave the complexes 1 ‐Ae (Ae=Mg, Ca, Sr, Ba) and 1 ‐Eu. 1 ‐Mg crystallized as a monomer while the heavier complexes crystallized as dimers. The Fe???Mg distance in 1 ‐Mg is too long for a bonding interaction, but short Fe???Ae distances in 1 ‐Ca, 1 ‐Sr, and 1 ‐Ba clearly support intramolecular Fe???Ae bonding. Further evidence for interactions is provided by a tilting of the Cp rings and the related ¹H NMR chemical‐shift difference between the Cp α and β protons. While electrochemical studies are complicated by complex decomposition, UV/Vis spectral features of the complexes support Fe→Ae dative bonding. A comprehensive bonding analysis of all 1 ‐Ae complexes shows that the heavier species 1 ‐Ca, 1 ‐Sr, and 1 ‐Ba possess genuine Fe→Ae bonds which involve vacant d‐orbitals of the alkaline‐earth atoms and partially filled d‐orbitals on Fe. In 1 ‐Mg, a weak Fe→Mg donation into vacant p‐orbitals of the Mg atom is observed.     

An Efficient Synthesis of 1,3‐Diphenyl‐3‐phenylamino‐propan‐1‐one and its Derivatives by Mannich Reaction in the Presence of Doped Porous Carbon by Nitrogen and Sulfur (NS‐PCS) as Catalyst

Synthesis of β‐amino carbonyl compounds by Mannich reaction involves the creation of various bonds in a single action and is attracting great attention as one of the most powerful synthetic tools for the expansion of molecular convolution and versatility. Carbon spheres (CSs) combine the advantages of carbon materials with spherical colloids, which gives them several inimitable features as catalysts. In this work, the reaction between acetophenone, aromatic aldehydes, and aromatic amines has been efficiently catalyzed by porous carbon spheres which were doped by nitrogen and sulfur (NS‐PCS) at ambient temperature to give diverse β‐amino carbonyl compounds in nearly high yields.