A synthesis of esters, amides, and sulfones bearing a 1-cyclopentenyl group at the α-position from cyclobutanones with one-carbon ring-expansion

Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from cyclobutanones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters, lithium enolate of carboxylic acid N,N-dimethylamides, or lithium α-carbanion of alkyl phenyl sulfones gave adducts in high yields. The adducts were treated with isopropylmagnesium chloride or ethylmagnesium chloride in dry toluene to give esters, amides, and sulfones bearing a 1-cyclopentenyl group at the α-position in moderate to good yields with one-carbon ring-expansion via magnesium carbenoid 1,2-CC insertion reaction. The magnesium carbenoid 1,2-CC insertion reaction proved to be highly stereospecific. The reaction mechanism and origin of the specificity are described.     

Enantioselective organocatalytic approach to δ-lactones bearing a fused cyclohexanone scaffold

A new method based on the cascade reaction between β,γ-unsaturated-α-ketophosphonates and cyclic 1,3-dicarbonyls is reported for the synthesis of highly enantiomerically enriched δ-lactones bearing a fused cyclohexenone scaffold. The target products bearing a δ-lactone moiety and one stereogenic center were obtained in good to excellent yields (83–96%) and enantioselectivities (63:32–95:5 er). The best results were obtained in the presence of a chiral Brønsted base catalyst derived from the cinchona alkaloid quinine and modified by a squaramide moiety.     

Cross-metathesis of allyl halides with olefins bearing an α-alkoxy amide group

We have examined whether the allyl halide cross-metathesis reaction tolerates α-alkoxy amide groups. Ruthenium-based catalysts I-III did not catalyze the cross-metathesis of allyl halides in the presence of an α-alkoxy N,N-dimethylamide group to any appreciable extent, but the reaction could tolerate either a bulky N,N-diisopropylamide or Weinreb amide group. In particular, the Grubbs-Hoveyda-Blechert 2nd generation catalyst (III) efficiently catalyzed the cross-metathesis of allyl halides with olefins bearing a Weinreb amide group.     

A porphyrin with a C═C unit at its center

The molecule (C═C)TTP (TTP = tetra-p-tolylporphyrin) and the triflate salt of its dication, [(C═C)TTP][OTf](2), have been synthesized and characterized. NMR spectroscopy, nucleus-independent chemical shift calculations, and the crystal structure of (C═C)TTP indicate that (C═C)TTP is antiaromatic and (C═C)TTP(2+) is aromatic.     

Oxyfunctionalization of ketones bearing α-methylene group with piperidine oxoammonium salt.Synthesis of α-diketones from monoketones

A facile method for the title transformation is described. The reaction of 2,2,6,6-tetramethyl-4-methoxypiperidine oxoammonium chloride (1b) and ketones bearing a-methylene group in acetonitrile proceeded smoothly to give the a-oxyfunctionalized coupling products (6a-h). These coupling products decomposed upon heating in acidic medium to produce a-diketones (7a-h) in good to excellent yields.     

A new determination of the structure of water at 25°C

The results of a new neutron diffraction experiment to measure the structure of water are presented. The data, measured at the McMaster Nuclear Reactor, are of a high quality and are analysed to yield the hydrogen-hydrogen pair correlation function using a subtraction procedure which has been used in previous experiments of this kind. This procedure circumvents the necessity of applying inelasticity corrections. The results are in good agreement with earlier work and serve to establish the general correctness of the subtraction procedure when used to determine hydrogen correlations. The data are further analysed to yield separate oxygen-hydrogen and oxygen-oxygen partial structure factors for liquid water. For the second part of the analysis an effective mass model of the dynamic scattering law is used, with the model parameter, the effective mass of the scattering particle, chosen by a least-squares fit to the measured differential cross sections. The final pair correlation functions are obtained using a maximum entropy analysis of the structure functions.     

A new ligand-functionalizedβ-cyclodextrin as a esterolytic reagent at neutral pH

The paper reports the synthesis of a-cyclodextrin (-CD) derivative (1) functionalized with a ligand subunit at the secondary-hydroxyl rim. The ligand subunit is 2-hydroxymethyl-6-thiomethyl pyridine connected to the macrocycle via a thioether bond. In the presence of Cu(II) ions1 accelerates the cleavage of thep-nitrophenyl esters of picolinic acid (PNPP), quinaldic acid (PNPQ) and its 6-phenyl derivative (PNPQPh) via the nucleophilic attack of the hydroxyl of the pyridine subunit. However, the-CD derivative is less effective than the ligand 2-hydroxymethyl-6-methylthiomethyl pyridine (2), indicating no cooperation between the hydrophobic and metal ion recognition sites. However, in the case of PNPQPh, the observed rate constants in the presence of Cu(II) ions are close to that of model2 and this suggests we are approaching a binding mode appropriate for taking advantage of the two binding sites of the metal receptor1 · Cu(II). Interestingly, the most reactive derivative with native-CD is thep-nitrophenyl quinaldate (PNPQ) in accord with its mode of complexation to the macrocycle and the location of the actual nucleophile (one of the secondary hydroxyls of-CD).     

A new route to heterocyclic α-dehydro α-amino esters

Heterocyclic α-dehydro α -amino esters are obtained by the reaction of ethyl N-carbomethoxy oxamate with ω-halogened phosphorus ylids.     

Synthesis and properties of group 9 metal complexes bearing a β-ketophosphenato ligand

A novel β-ketophosphenato ligand bearing a bulky substituent, Tbt(2,4,6-tris[bis(trimethylsilyl)methyl]phenyl), on the phosphorus atom was newly designed and synthesized as a heavier congener of a β-ketoiminato ligand. Rhodium and iridium complexes bearing this new β-ketophosphenato ligand have been synthesized and fully characterized by spectroscopic and elemental analyses together with X-ray crystallographic analyses. The results of NMR spectroscopic studies and the X-ray structural analyses suggested that the β-ketophosphenato ligand has unique electronic features due to the low-coordinated phosphorus atom. Comparison of properties between rhodium β-ketophosphenates 2a,b and rhodium β-ketoiminate 7 revealed the character of the β-ketophosphenato ligand, where the trans influence of the phosphorus atom should be stronger than the nitrogen atom of the β-ketoiminato ligand.     

A neighbouring group effect leading to enhanced nucleophilic substitution of amines at the hindered α-carbon atom of an α-hydroxyphosphonate

Diethyl α-hydroxy-benzylphosphonate undergoes nucleophilic substitution with primary amines of sufficient reactivity at around 100 °C to afford the corresponding α-aminophosphonates. The substitution can be enhanced by microwave irradiation. The reaction takes place with surprising ease due to the neighbouring group effect of the PO moiety as was justified by DFT calculations carried out to evaluate the mechanism of the substitution under discussion.     

Chiral recognition in aqueous solutions. Preferential configurations of α-aminoacids bearing substituted alkyl chains at 25°C

Calorimetric measurements were carried out at 25°C on binary and ternary aqueous solutions containing L and D forms fo the following -aminoacids: tryptophan, cysteine, methionine, phenylalanine, histidine, threonine, and citrulline, which contain both hydrophilic and hydrophobic domains. Differences were found between the values of the homochiral and heterochiral pairwise enthalpic interaction coefficients for tryptophan, cysteine, and methionine. To the contrary, chiral recognition was not detected for phenylalanine, histidine, citrulline, and threonine. The data were interpreted in terms of a preferential configuration model. Chiral recognition is detected only when the interactions of the side chains in the homo- and heterochiral configurations are different. Chiral recognition disappears when a competition exists between zwitterion-zwitterion interactions and side chain-side chain interactions. In some cases, such as for citrulline, compensation effects can occur due to thermal contributions from different domains which mask chiral recognition.     

Synthesis and bioactivity of α-galactosylceramide analogues bearing an aryl group within the fatty amide chain

We describe the synthesis and bioactivity of analogues of α-galactosylceramide (1) bearing a long-chain alkyl group substituted at the meta or para position of an aryl group embedded within the amide chain. We compared the ability of these compounds and of 1 and C6Ph (2, which has a phenyl group at the amide chain terminus) to stimulate murine invariant Natural Killer T cells and to dock with human CD1d.     

Synthesis of polyfunctionalized pyrroles bearing C-2 α-azido side-chains and displacement of the α-azido group by various nucleophiles

Tetrasubstituted pyrroles bearing C-2 α-azido side-chains were synthesized employing a new class of diazides, α,γ-diazido α,β-unsaturated esters, and 1,3-dicarbonyl compounds under simple thermal conditions. Further investigation of the synthetic utility of the obtained pyrroles reveals unexpected displacement of the α-azido group at the C-2 side-chain by a variety of nucleophiles. This two-step process exhibits a broad substrate scope, good functional group tolerance, simple operation, and high reaction efficiency, providing an easy access to polyfunctional pyrroles with novel substitution patterns.     

A new route to α-alkyl-α-fluoromethylenebisphosphonates

A new route to α-alkyl-α-fluoromethylenebisphosphonates, 2 has been developed starting from commercially available tetraethyl fluoromethylenebisphosphonate (1), and alkyl halides using either caesium carbonate in DMF or sodium dimsyl. De-esterification of 2 provided biologically important α-alkyl-α-fluoromethylenebisphosphonic acid, 3, while alkoxide-induced carbon-phosphorus bond cleavage of 2 gave α-fluorophosphonates, 4, which are useful synthons in organic synthesis.     

Unusual α-glycosylation with galactosyl donors with a C2 ester capable of neighboring group participation

Glycosylation of 4-methoxyphenyl 2,3,6-tri-O-benzoyl-β-d-glucopyranoside (2) with isopropyl 3-O-allyl-2,4,6-tri-O-benzoyl- (9) or 6-O-allyl-2,3,4-tri-O-benzoyl-1-thio-β-d-galactopyranoside (7) as the donor, afforded an α- and β-linked mixture, whereas with isopropyl 3-O-chloroacetyl-2-O-benzoyl-4,6-O-benzylidene- (13) and isopropyl 3-O-allyl-2-O-benzoyl-4,6-O-benzylidene-1-thio-β-d-galactopyranoside (15) as the donor, glycosylation of 2 gave α-linked products only, indicating that 4,6-O-benzylidenation led to α-stereoselectivity in spite of the C2 ester capable of neighboring group participation. Using 15 as the donor, glycosylation of mannose derivatives with 2- or 3-OH's, glucose with 2- or 3-OH's, galactose with 2-, or 3-, or 4-OH's, glucosamine and glucuronic acid with a 4-OH, and a lactose derivative with a 4-OH, also furnished α-linked products. However, when using 15 as the donor, glycosylation of aglycon alcohol or sugars with 6-OH's yielded normal β-linked products.     

Synthesis of a β-cyclodextrin derivative bearing an azobenzene group on the secondary face

An oxidative coupling Sonogashira-type reaction has been used to synthesize a β-cyclodextrin derivative bearing an azobenzene group on the secondary face for the first time starting from a β-cyclodextrin propargylated at one of its C-2 positions. The de-O-propargylation reaction and the formation of an oxidative homocoupling dimer were found to compete with the desired product under several Sonogashira-type reaction conditions. However, the use of a diluted reductive atmosphere of H₂ avoided the former and diminished the latter.     

5-Aryl-2,2′-bipyridines bearing fluorinated anilines residues at C6 position: synthesis and photophysical properties

Research on Chemical Intermediates - A convenient synthetic approach to 5-aryl-2,2′-bipyridines bearing a (poly)fluorine-containing aniline residue at position C6 based on sequential...     

A new reaction of diazomethane with norbornyl α-diketones

A new reaction of diazomethane with norbornyl α-diketones in MeOH as solvent leading regioselectively to ketals is described. The mechanistic details of this intriguing reaction were investigated employing d₄-MeOH, EtOH and d₆-EtOH. The surprising observation of complete deuterium incorporation in the diazomethane-derived methoxy group was accounted for by sequential deuterium exchange between the initially formed hemiketal d₄-18 and diazomethane in the presence of d₄-MeOH as solvent.     

Enantioselective organocatalytic synthesis of quaternary α-amino acids bearing a CF3 moiety

A highly enantioselective Friedel-Crafts reaction catalyzed by a chiral phosphoric acid was developed. N-Boc-protected ethyl trifluoropyruvate imine was activated by 6 mol % of catalyst and reacted with a wide variety of indole derivatives to afford quaternary α-amino acids in excellent yields (up to 99%) and high enantioselectivities (up to 98:2 er).