Regio- and chemoselective metalation of arenes and heteroarenes using hindered metal amide bases

The preparation of highly functionalized organometallic compounds can be achieved by direct C H activation of a broad range of unsaturated substrates using lithium chloride solubilized 2,2,6,6‐tetramethylpiperidide bases (TMP_nMX_m⋅p LiCl). These are excellent reagents for converting a wide range of aromatic and heterocyclic substrates into valuable organometallic reagents with broad applications in organic synthesis.     

An efficient chemoselective etherification of phenols in polyfunctional aromatic compounds

A simple and efficient chemoselective alkylation of phenols in polyfunctional aromatic compounds with different alkyl halides in the presence of K₂CO₃/TBAB is reported. The method is successful with various hydroxy aromatic acids or oximes possessing other functional groups.     

Post-source decay of alkylated and functionalized polycyclic aromatic compounds

Post-source decay (PSD) is a valuable tool for providing structural information from large molecules by time-of-flight mass spectrometry (TOFMS). We used PSD to obtain this type of data from small molecules in the laser desorption/ionization (LDI) study of diesel engine exhaust particles. As the original nitrogen laser (lambda = 337 nm, E = 3.5 eV/photon) of our TOF mass spectrometer does not yield sufficient energy to ionize polycyclic aromatic hydrocarbons (PAHs), a second laser with a shorter wavelength has been coupled to the instrument. The fourth harmonic of a Nd:YAG laser (lambda = 266 nm, 4.6 eV/photon) has been chosen to achieve two-photon single-step desorption/ionization of PAHs. The PSD fragmentation of functionalized, alkylated and sulfur PAHs is discussed. Diesel engine exhaust particles are also studied as an example of a real complex sample. This technique is presented herein as a way to identify small molecules in environmental samples. Information provided by LDI-PSD-TOFMS can be a way to distinguish pollutants with very close molecular weights even if the resolving power of a TOF mass spectrometer is not sufficient.     

Structurally-defined direct C-magnesiation and C-zincation of N-heterocyclic aromatic compounds using alkali-metal-mediated metallation

Demonstrating direct synergic "low polarity metallation", 1-methylindole is C-magnesiated by (TMEDA)(2).Na(2)MgBu(4) and C-zincated by (TMEDA).Na((t)Bu)(TMP)Zn((t)Bu), and 1-methylpyrrole is C-zincated by the same reagent, with all three metal products successfully crystallographically characterised.     

Regio- and chemoselective catalytic transfer hydrogenation of aromatic nitro and carbonyl as well as reductive cleavage of azo compounds over novel mesoporous NiMCM-41 molecular sieves

[reaction: see text] [corrected] Regio- and chemoselective reduction of nitroarenes and carbonyl compounds and reductive cleavage of azo compounds, including bulkier molecules, was achieved by the catalytic transfer hydrogenation method (CTH) using a novel nickel-containing mesoporous silicate (NiMCM-41) molecular sieve catalyst. In addition, the catalyst was also found to behave as a truly heterogeneous catalyst as the yield was practically unaffected.     

Regio- and chemoselective multiple functionalization of pyrimidine derivatives by selective magnesiations using TMPMgCl.LiCl

Successive regio- and chemoselective magnesiations of pyrimidines using TMPMgCl.LiCl furnish, after trapping with various electrophiles, highly functionalized derivatives in good to excellent yields. Applications to the synthesis of antiviral and anti-inflammatory agents such as p38 and sPLA2 kinase inhibitors are reported.     

An aluminum ate base: its design, structure, function, and reaction mechanism

An aluminum ate base, i-Bu(3)Al(TMP)Li, has been designed and developed for regio- and chemoselective direct generation of functionalized aromatic aluminum compounds. Direct alumination followed by electrophilic trapping with I(2), Cu/Pd-catalyzed C-C bond formation, or direct oxidation with molecular O(2) proved to be a powerful tool for the preparation of 1,2- or 1,2,3-multisubstituted aromatic compounds. This deprotonative alumination using i-Bu3Al(TMP)Li was found to be effective in aliphatic chemistry as well, enabling regio- and chemoselective addition of functionalized allylic ethers and carbamates to aliphatic and aromatic aldehydes. A combined multinuclear NMR spectroscopy, X-ray crystallography, and theoretical study showed that the aluminum ate base is a Li/Al bimetallic complex bridged by the nitrogen atom of TMP and the alpha-carbon of an i-Bu ligand and that the Li exclusively serves as a recognition point for electronegative functional groups or coordinative solvents. The mechanism of directed ortho alumination reaction of functionalized aromatic compounds has been studied by NMR and in situ FT-IR spectroscopy, X-ray analysis, and DFT calculation. It has been found that the reaction proceeds with facile formation of an initial adduct of the base and aromatic, followed by deprotonative formation of the functionalized aromatic aluminum compound. Deprotonation by the TMP ligand rather than the isobutyl ligand was suggested and reasoned by means of spectroscopic and theoretical study. The remarkable regioselectivity of the ortho alumination reaction was explained by a coordinative approximation effect between the functional groups and the counter Li(+) ion, enabling stable initial complex formation and creation of a less strained transition state structure.     

A novel strategy for the preparation of arylhydroxylamines: chemoselective reduction of aromatic nitro compounds using bakers' yeast

Using bakers' yeast as a biocatalyst, the chemoselective reduction of aromatic nitro compounds bearing electron-withdrawing groups gave the corresponding hydroxylamines with good to excellent conversion under mild conditions.     

Regio- and chemoselective covalent immobilization of proteins through unnatural amino acids

A general approach was developed for the regio- and chemoselective covalent immobilization of soluble proteins on glass surfaces through an unnatural amino acid created by post-translationally modifying the cysteine residue in a CaaX recognition motif with functional groups suitable for "click" chemistry or a Staudinger ligation. Farnesyl diphosphate analogues bearing omega-azide or omega-alkyne moieties were attached to the cysteine residue in Cys-Val-Ile-Ala motifs at the C-termini of engineered versions of green fluorescent protein (GFP) and glutathione S-transferase (GST) by protein farnesyltransferase. The derivatized proteins were attached to glass slides bearing linkers containing azide ("click" chemistry) or phosphine (Staudinger ligation) groups. "Click"-immobilized proteins were detected by fluorescently labeled antibodies and remained attached to the slide through two cycles of stripping under stringent conditions at 80 degrees C. GFP immobilized by a Staudinger ligation was detected by directly imagining the GFP fluorophore over a period of 6 days. These methods for covalent immobilization of proteins should be generally applicable. CaaX recognition motifs can easily be appended to the C-terminus of a cloned protein by a simple modification of the corresponding gene, and virtually any soluble protein or peptide bearing a CaaX motif is a substrate for protein farnesyltransferase.     

Highly chemoselective reduction of aromatic nitro compounds by copper nanoparticles/ammonium formate

A highly chemoselective reduction of aromatic nitro compounds to the corresponding amino derivatives has been achieved by a combination of copper nanoparticles and ammonium formate in ethylene glycol at 120 degrees C. The reductions are successfully carried out in presence of a wide variety of other reducible functional groups in the molecule, such as Cl, I, OCH2Ph, NHCH2Ph, COR, COOR, CN, etc. The reactions are very clean and high yielding.     

Regio- and chemoselective transfer hydrogenation of quinolines catalyzed by a CpIr complex

An efficient method for the transfer hydrogenation of quinolines catalyzed by a Cp^∗Ir complex was developed. A variety of 1,2,3,4-tetrahydroquinolines were obtained by regio- and chemoselective transfer hydrogenation of quinolines using 2-propanol as a hydrogen source.     

Cobalt(II) schiff base functionalized mesoporous silica as an efficient and recyclable chemoselective acetalization catalyst

Cobalt(II) Schiff base functionalized mesoporous silica was synthesized from covalent attachment via the introduction of Co(OAc)₂ to salicylaldimine functionalized mesoporous silica. The catalyst proved to be chemoselective one for the acetalization of aldehydes to the corresponding acetals in alcohol. The immobilized catalyst can be easily recovered and reused for at least ten reaction cycles without significant loss of its catalytic activity.     

Synthesis of dye functionalized xerogels via nucleophilic aromatic substitution of fluoro aromatic compounds with aminosilanes

The one-pot synthesis of inorganic–organic hybrid materials via combination of sol–gel process and nucleophilic aromatic substitution reaction of various fluoro aromatic compounds and 3-aminopropyltrimethoxysilane has been studied. Both, nucleophilic aromatic substitution reaction and sol–gel process can be accomplished in the same reaction vessel due to the sol–gel precursor tetraethoxysilane acting as solvent during the first reaction step. Hydrogen fluoride, which forms as a by-product of the substitution reaction, is trapped by both silane species present and subsequently serves as catalyst during the sol–gel process. The obtained materials can be classified as type II xerogels, because of the covalent linkage between organic chromophor and inorganic silicon network. Fluoro aromatic compounds with different reactivities for nucleophilic aromatic substitution reactions containing azo, azomethine, and diphenylamine groups were used in order to (1) demonstrate the synthetic concept and (2) fine-tune the optical properties of the resulting chromophoric xerogels. The final chromophor content within the xerogels was varied by modifying the ratio of organosilicon precursor and tetraethoxysilane. All obtained organic–inorganic hybrid materials were characterized in detail using solid state NMR- and UV/vis spectroscopy. Latter one gave experimental confirmation of the partial hydrolysis of azomethine dyes in the xerogels, while no decomposition of azo or diphenylamine dyes was observed.     

Synthesis of functionalized polycyclic compounds via a novel aromatic oxy-Cope rearrangement

Polycyclic compounds have been prepared by aromatic dianionic oxy-Cope rearrangements involving the π bonds of two phenyl rings in a [3,3] sigmatropic rearrangement.     

Regio- and stereoselective synthesis of functionalized N-Boc-2-alkynylcyclopropylamines

Russian Chemical Bulletin -     

Toward a protecting-group-free halogen-metal exchange reaction: practical, chemoselective metalation of functionalized aromatic halides using dianion-type zincate, tBu4ZnLi2

A versatile preparation method for aromatic zincate compounds through a halogen-zinc exchange reaction using dilithium tetra-tert-butylzincate (tBu4ZnLi2) has been developed. This reagent permits efficient preparation of highly functionalized aromatic zincates, particularly, those with electrophilic functional groups, such as ester, amide, alcohol, and phenol. Halogen-zinc exchange reactions followed by electrophilic trapping (with allyl bromide or benzaldehyde) proved to be a powerful tool for C-C bond formation on functionalized aromatic rings. The functionalized aromatic zincate intermediate was also found to undergo copper- and palladium-catalyzed C-C bond-forming reactions with good yields and high chemoselectivity.     

The first chemoselective synthesis of functionalized 3-vinylpyrroles

3-(1-Alkylthio-2-cyano-2-X-ethenyl)pyrroles (X=CN, CONH₂, CO₂Et) have been synthesized in 28-58% yields by the reaction of pyrrole-3-carbodithioates with CH-acids (malononitrile, cyanoacetamide, cyanoacetate) in the KOH-DMSO system.     

Highly effective and chemoselective hydrodeoxygenation of aromatic alcohols

Effective hydrodeoxygenation (HDO) of aromatic alcohols is very attractive in both conventional organic synthesis and upgrading of biomass-derived molecules, but the selectivity of this reaction is usually low because of the competitive hydrogenation of the unsaturated aromatic ring and the hydroxyl group. The high activity of noble metal-based catalysts often leads to undesired side reactions (e.g., saturation of the aromatic ring) and excessive hydrogen consumption. Non-noble metal-based catalysts suffer from unsatisfied activity and selectivity and often require harsh reaction conditions. Herein, for the first time, we report chemoselective HDO of various aromatic alcohols with excellent selectivity, using porous carbon–nitrogen hybrid material-supported Co catalysts. The C–OH bonds were selectively cleaved while leaving the aromatic moiety intact, and in most cases the yields of targeted compounds reached above 99% and the catalyst could be readily recycled. Nitrogen doping on the carbon skeleton of the catalyst support (C–N matrix) significantly improved the yield of the targeted product. The presence of large pores and a high surface area also improved the catalyst efficiency. This work opens the way for efficient and selective HDO reactions of aromatic alcohols using non-noble metal catalysts.

Porous carbon–nitrogen hybrid material-supported Co catalysts can effectively promote the chemoselective hydrodeoxygenation reaction of a various of aromatic alcohols in ethanol and hydrogen atmosphere, under relatively mild conditions.     

Deprotonative metalation using ate compounds: synergy, synthesis, and structure building

Historically, single-metal organometallic species such as organolithium compounds have been the reagents of choice in synthetic organic chemistry for performing deprotonation reactions. Over the past few years, a complementary new class of metalating agents has started to emerge. Owing to a variable central metal (magnesium, zinc, or aluminum), variable ligands (both in their nature and number), and a variable second metallic center (an alkali metal such as lithium or sodium), "ate" complexes are highly versatile bases that exhibit a synergic chemistry which cannot be replicated by the homometallic magnesium, zinc, or aluminum compounds on their own. Deprotonation accomplished by using these organometallic ate complexes has opened up new perspectives in organic chemistry with unprecedented reactivities and sometimes unusual and unpredictable regioselectivities.