Stereocomplementary bioreduction of alpha,beta-unsaturated dicarboxylic acids and dimethyl esters using enoate reductases: enzyme- and substrate-based stereocontrol

Asymmetric bioreduction of alpha,beta-unsaturated dicarboxylic acids, such as 2-methylmaleic/fumaric and 2-methylenesuccinic acid, as well as the corresponding dimethyl esters, using three cloned enoate reductases furnished 2-methylsuccinic acid or dimethyl 2-methylsuccinate, respectively. Opposite stereoisomeric products were obtained in up to >99% ee either by choice of the enzyme or by using E/Z-configurated substrates. Cofactor-recycling systems (NADH/FDH/formate, NADH/GDH/glucose or NADPH/G6PDH/glucose-6-phosphate) only worked in presence of a divalent metal ion, such as Ca2+, Mg2+, or Zn2+.     

Synthesis, characterization, anti-inflammatory and in vitro antimicrobial activity of some novel alkyl/aryl substituted tertiary alcohols

The synthesis of some novel alkyl/aryl substituted tertiary alcohols was accomplished in two steps. The synthetic route involves preparation of Grignard reagents by treating alkyl/aryl bromides with magnesium turnings in dry ether. Then substituted chalcones were reacted with the Grignard reagents to afford alkyl/aryl substituted tertiary alcohols 1-10. The structures of the synthesized compounds were assigned on the basis of FT-IR, 1H-NMR, 13C-NMR and mass spectroscopic data. The in vivo anti-inflammatory activity of the synthesized compounds was evaluated using the carrageenan-induced hind paw edema method and was compared with that of ibuprofen. Some of the newly synthesized compounds showed promising anti-inflammatory activity. The tertiary alcohols 1-10 were also screened for antibacterial activity against ten bacterial strains using seven Gram-positive and three Gram-negative bacteria and for antifungal activity against Aspergillus Flavus, Aspergillus Niger and Aspergillus pterus. Tertiary alcohols 1-10 were found to exhibit good to excellent antimicrobial activities compared to levofloxacin and fluconazole used as standard drugs.     

Synthesis,characterization and catalytic applications of rhodium(I) organometallics with substituted tertiary phosphines

Organometallics of the type [Rh(COD)(L)Cl] (where, L = carboxyl/formyl/pyridyl tertiary phosphines) have been synthesized by treating the precursor [Rh(COD)Cl]₂ with substituted tertiary phosphines. [Rh(COD)(Ph₂P-2-C₆H₄COO)] and [Rh(COD)(Ph₂P-CH₂COO)] were synthesized by halide abstraction from the precursor [Rh(COD)Cl]₂ in the presence of AgPF₆ in tetrahydrofuran by involving 2-carboxy phenyl/carboxy methyl group of tertiary phosphines in coordination as bidentate ligands. Similarly, the cationic compounds of the type [Rh(COD)L₂]PF₆ were also synthesized by treating [Rh(COD)Cl]₂ in the presence of AgPF₆. All these compounds were characterized by elemental analysis, conductance measurements, IR, ¹H, ¹³C, ³¹P NMR, mass, and electronic spectral studies. [Rh(COD)(Ph₂-P-2-C₆H₄COOH)Cl] and [Rh(COD)(Ph₂-P-2-C₆H₄COO)] were studied on the catalytic reduction reactions of 2-nitroanisole, 3-nitro anisole, 4-nitroanisole, 2-nitrobenzoicacid, 3-nitrobenzoicacid, 4-nitrobenzoicacid under mild conditions and [Rh(COD)(Ph₂-P-2-C₆H₄COO)] was found to be more efficient than [Rh(COD)(Ph₂-P-2-C₆H₄COOH)Cl]. This article is dedicated to Dr. D. R. M Walton, who successfully completed his tenure as Editor-in-Chief, Transition Metal Chemistry.     

Radical fixation of functionalized carbon resources: alpha-sp3C-H carbamoylation of tertiary amines with aryl isocyanates

A new carbamoylation of tertiary amines is reported. This rare C-H transformation features the direct generation of alpha-aminoalkyl radicals from tertiary amines, followed by the addition of the resultant nucleophilic radicals to isocyanates, enabling unique access to N,N-dialkylated amino acid derivatives. The authors put forward a mechanistic proposal that is based on the isolation of borinamides produced by capturing nitrogen radical intermediates with Et3B. The present transformation provides a novel one-step process for producing mepivacaine, a clinically important local anesthetic, from readily available materials.     

Carbon-based leaving group in substitution reactions: functionalization of sp3-hybridized quaternary and tertiary benzylic carbon centers

Lewis acid promoted substitution reactions employing Meldrum's acid and 5-methyl Meldrum's acid as carbon-based leaving groups are described which transform unstrained quaternary and tertiary benzylic C(sp(3))-C(sp(3)) bonds into C(sp(3))-X bonds (X = C, H, N). Importantly, this reaction has a broad scope in terms of both suitable substrates and nucleophiles with good to excellent yields obtained (typically >90%).     

Ligand effects in the formation of tertiary carbanions from substituted tertiary aromatic amides

Reaction of 2‐isopropyl‐(N,N‐diisopropyl)‐benzamide 5 with tBuLi in ether results in ortho deprotonation and the formation of a hemisolvate based on a tetranuclear dimer of ( 5 ‐Li_o)₂?Et₂O. The solid‐state structure exhibits a dimer core in which the amide oxygen atoms fail to stabilize the metal ions but are instead available for interaction with two metalated monomers that reside peripheral to the core. Reaction of 5 with tBuLi in the presence of the tridentate Lewis base PMDTA (N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine) takes a different course. In spite of the tertiary aliphatic group at the 2‐position in 5 , X‐ray crystallography revealed that a remarkable benzylic (lateral) deprotonation had occurred, giving the tertiary benzyllithium 5 ‐Li_l?PMDTA. The solid‐state structure reveals that amide coordination and solvation by PMDTA combine to distance the Li⁺ ion from the deprotonated α‐C of the 2‐iPr group (3.859(4) Å), thus giving an essentially flat tertiary carbanion and a highly distorted aromatic system. DFT analysis suggests that the metal ion resides closer to the carbanion center in solution. In line with this, the same (benzylic) deprotonation is noted if the reaction is attempted in the presence of tridentate diglyme, with X‐ray crystallography revealing that the metal is now closer to the tertiary carbanion (2.497(4) Å). Electrophilic quenches of lithiated 5 have allowed, for the first time, the formation of quaternary benzylic substituents by lateral lithiation.     

Through-space intramolecular palladium rearrangement in substituted aryl complexes: theoretical study of the aryl to alkylpalladium migration process

DFT/B3LYP calculations have been carried out to study intramolecular 1,n palladium shifts (n = 3-5) between sp2 and sp3 carbon atoms in alkylarylpalladium systems. Such shifts, which also involve a concomitant exchange with a hydrogen atom of the alkylaryl ligand, are quite often a pivotal step of several organic transformations mediated by palladium complexes. We show that the intimate mechanism for the 1,3 shift corresponds to a Pd(IV) pathway, whereas a Pd(II) pathway is favored in the case of 1,5 migrations. In the case of 1,4 migrations, both mechanisms are competitive. The Pd(IV) pathway can involve either a true Pd(IV) intermediate (oxidative addition/reductive elimination mechanism) or a Pd(IV) transition state (oxidative hydrogen migration mechanism). The energy barrier is very high for the 1,3 palladium shift, making this process very unlikely, in contrast to the other ones which have enthalpy barriers ranging between 22.8 kcal mol-1 (for the 1,5 shift) and 31.9 kcal mol-1 (for the least favorable 1,4 shift studied here). All of these results are in line with our previous results for palladium shifts between two sp2 carbon atoms. In addition, the sp2 to sp3 shifts have been found to be rather exothermic owing to the possibility for the alkylaryl ligand in the product to achieve a eta3 coordination mode. This eta3 coordination mode results either from the shift itself (1,3 case) or from a subsequent rearrangement that comprises a chain-running mechanism within the alkyl chain bound to the metal (for n > 3).     

The 13C NMR spectra,isomerism, and conformational analysis of substituted piperidin-4-ones

The ¹³C NMR spectra of 15 stereoisomers of 1-mono-, 1,2-di-, and 1,2,5-trisubstituted piperidin-4-ones were investigated, and the stereochemical orientations of the substituents and the conformation relationships were established. For the series of piperidones a method for determination of the absolute confirmation of the C₍₂₎ center of the piperidone ring is proposed on the basis of the chemical shifts of the methyl groups in the 1-s--phenylethyl substituent at the nitrogen atom in the preferred rotamers with respect to the C₍₁₎-N bond.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1503–1515, November, 1986.     

The preparation of, and electrochemical studies on, some substituted aryl dithiadiazolylium salts and dithiadiazolyl radicals

A series of aryl-substituted 1,2,3,5-dithiadiazolylium cations (I) and 1,3,2,4-dithiadiazolylium cations (II) were prepared as their hexafluoroarsenate(V) salts using standard methods. Electrochemical studies on I and II showed reversible one-electron reductions. The half-wave reduction potentials for a series of meta-substituted derivatives of both I and II exhibited a linear free energy relationship with the Hammett parameter, σ_m. The small value of the reaction constant, , for both meta and para-derivatives indicates that electronic effects are small and in the case of the ortho-derivatives of II, steric effects dominate the redox process. Reduction of the 1,2,3,5-dithiadiazolylium cations, as their chloride salts, yielded the corresponding dithiadiazolyl radicals (III).     

Stereoselective formation of tertiary and quaternary carbon centers via inverse conjugate addition of carbonucleophiles to allenic esters

Stereoselective inverse conjugate addition of carbonucleophiles to allenoates bearing a chiral auxiliary in the ester moiety afforded optically active α,β-unsaturated carboxylic esters bearing a new stereocenter at the δ position. The rationalization of the observed selectivity was supported by semi-empirical molecular orbital calculations.     

The application of aryl substituted derivatives of xylose as environmentally friendly multipurpose pesticides

A series of aryl substituted derivatives of xylose have been synthesized. Biological tests have revealed high fungicidal activity of the resulting compounds against various phythopathogenic fungi. Additional biological studies have demonstrated high plant growth regulatory activity of the compounds synthesized.     

Absorption and fluorescence properties of aryl substituted porphyrins in different media

Absorption and fluorescence properties of aryl substituted porphyrins, 5,10,15,20-tetra-4-oxy(aceticacid)phenylporphyrin (TAPP), 5,10,15,20-tetra-(4-phenoxyphenyl) porphyrin (TPPP), 5,10,15,20-tetra-(3-bromo-4-hydroxyphenyl) porphyrin (TBHPP), and 5,10,15,20-tetra-p-chloromethylphenyl porphyrin (CMPP) were investigated. The UV/vis absorption, fluorescence and excited spectra as the fluorescence quantum yields and fluorescence lifetimes for the compounds were measured in organic solvents (chloroform (CHCl₃), tetrahydrofuran (THF)) and immobilized media (PVC film, sol–gel matrix). The fluorescence quantum yields of TAPP and TPPP were higher than the others. The fluorescence lifetimes of all studied porphyrin derivates were found to be fifty percent lower and their fluorescence intensities were increased fifty percent more in both of immobilized mediums, as compared to organic solvents.     

Metal-organic frameworks for electrochemical reduction of carbon dioxide: The role of metal centers

Direct electrochemical reduction of CO_2 into valuable chemicals and fuel is one of the most promising approaches to address the current energy crisis and lower CO_2 emission. Recently, numerous metal-organic framework(MOF) and their derived materials have extensively been developed as electrocatalysts for CO_2 reduction owing to their unique structure including porosity, large specific surface area, and tunable chemical structures. In this review, the recent progress of MOF-based electrocatalysts for CO_2 reduction was summarized and discussed. Detailed discussions mainly focus on the synthesis and mechanism of pristine MOFs and MOF-derived materials for electrocatalytic CO_2 reduction. These examples are expected to provide clues to rational design and synthesis of stable and high-performance MOFs-based electrocatalysts for CO_2 reduction.     

Electrophilic carbon transfer in gold catalysis: synthesis of substituted chromones

Using easily accessible aromatic alkoxy-arylalkynones, we have investigated the gold-catalyzed intramolecular addition of ethers to alkynes, to give easy access to various substituted chromones. This reaction involves the transfer of the ether substituent via a carbodemetallation process. We also noticed a competing isomerization of several starting materials for which we propose a second gold catalyzed mechanism.     

Palladium-catalyzed regio- and diastereo-selective allylic alkylation using 2-(diphenylphosphino)benzoic acid: construction of vicinal quaternary and tertiary carbon centers

The palladium-catalyzed regio- and diastereo-selective allylic alkylation of allyl acetates with carbon nucleophiles occurred. The stereochemistry was highly controlled by the palladium catalyst with 2-(diphenylphosphino)benzoic acid as the ligand, and vicinal quaternary and tertiary carbon centers were constructed.     

The influence of alkylene spacers on conformational and thermal properties of poly (aryl methacrylates)

The effect of introducing alkylene spacers on the thermal and conformational properties of poly(aryl methacrylates) has been studied. Poly(2-phenylethyl-1-methacrylate) (PPEMA) and poly(4-phenylbutyl-1-methacrylate) (PPBMA) samples of narrow poly-dispersities and covering a very broad range of molecular weights were produced by free radical solution polymerization, followed by fractionation. These materials were studied by a combination of differential scanning calorimetry, light scattering, and viscometry measurements to allow evaluation of their glass transition temperatures (T_g) and characteristic ratios (C_∞). These results are compared with literature data available for poly(phenyl methacrylate) (PPMA), which has no alkylene spacer, and poly(benzylmethacrylate) (PBMA), which has a methylene spacer. A progressive decrease in T_g is observed as the length of the alkylene spacer is increased, reflecting the enhancement of side group (local) flexibility. C_∞ decreases substantially on going from PPMA to PBMA but then increases on going to PPEMA and PPBMA. This behavior is attributed to the fact that while side group flexibility increases for the materials with longer alkylene spacers, and this would be expected to decrease C_∞, the side group size is progressively increasing. Larger side groups generally increase C_∞ of polymethacrylates. Thus the observed C_∞ behavior for these polymers reflects both the size and flexibility of the substituents. © 1994 John Wiley & Sons, Inc.