Enantioselective Catalysis. Part 156 [1]. Ruthenium Procatalysts and 2-Pyridinealdehyde/( S)- NOBIN-Derived Cocatalysts in the Transfer Hydrogenation of Acetophenone with 2-Propanol

Several ruthenium procatalysts were tested in the transfer hydrogenation of acetophenone with 2-propanol using the chiral imine ligand (S)-2-(2-pyridinylmethyleneamino)-2-hydroxy-1,1-binaphthyl and the corresponding amine (S)-2-(2-pyridinylmethylamino)-2-hydroxy-1,1-binaphthyl. Ru(PPh ₃)₃Cl₂ was the best procatalyst. Its triphenylphosphane ligands were crucial for the catalytic activity and take part in the chirality transfer. Triphenylphosphane removing reagents such as copper(I) chloride, TEMPO, or TMAO improved the catalytic performance to enantioselectivities up to 99% ee. The findings led to a mechanistic proposal including dissociation equilibria of triphenylphosphane and chelate ring opening of the tridentate chiral binaphthyl ligand. New ligands with an additional chiral center were synthesized and tested as cocatalysts. The nature of catalytically active intermediates was examined by MS and NMR spectroscopy.     

Synthesis of (2<Emphasis Type="Italic">S</Emphasis>,3<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>)-2,3-<Emphasis Type="Italic">O</Emphasis>-isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one

(2S,3S,4S)-2,3-O-Isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one was synthesized starting from D-ribose through methyl (Z)-3-(5-acetyl-2,2-acetoxyacetyl-2,2-dimethyl-1,3-dioxolan-4-yl)prop-2-enoate which was subjected to cyclization in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene, followed by decarboxylation.     

Mono-<Emphasis Type="Italic">meso</Emphasis>-<Emphasis Type="Italic">tert</Emphasis>-butylporphyrin

Summary. Treatment of meso-tetra(tert-butyl)porphyrin with sulfuric acid/n-butanol affords a mixture of porphyrin and mono-tert-butylporphyrin in relatively high yield.     

Enantioselective Catalysis CXLI [1]. Tridentate Ligands with 1-(Pyridin-2-yl)ethylamine as Chiral Building Block in the Enantioselective Transfer Hydrogenation of Acetophenone

Summary.  A series of novel tridentate ligands with nitrogen and oxygen donor sites was synthesized starting from enantiomerically pure (S)- and (R)-1-(pyridin-2-yl)ethylamine, the preparation and resolution of which was developed. The new optically active ligands were tested as in situ catalysts together with Ru(PPh₃)₃Cl₂ in the enantioselective transfer hydrogenation of acetophenone with isopropanol. The secondary amine ligand (S)-2,4-di-tert-butyl-6-(1-(pyridin-2-yl)ethylamino)methylphenol gave the best results with almost quantitative conversion and 47%ee. Received August 17, 2001. Accepted August 27, 2001     

Heat capacities and thermodynamic properties of (<Emphasis Type="Italic">S</Emphasis>)-<Emphasis Type="Italic">tert</Emphasis>-butyl 1-phenylethylcarbamate

An N-tert-butyloxycarbonylated organic synthesis intermediate, (S)-tert-butyl 1-phenylethylcarbamate, was prepared and investigated by means of differential scanning calorimetry (DSC) and thermogravimetry (TG). The molar heat capacities of (S)-tert-butyl 1-phenylethylcarbamate were precisely determined by means of adiabatic calorimetry over the temperature range of 80-380 K. There was a solid–liquid phase transition exhibited during the heating process with the melting point of 359.53 K. The molar enthalpy and entropy of this transition were determined to be 29.73 kJ mol⁻¹ and 82.68 J K⁻¹ mol⁻¹ based on the experimental C _p–T curve, respectively. The thermodynamic functions, [H_T⁰ - H_298.15⁰ H_{T}^{0} - H_{298.15}^{0} ] and [S_T⁰ - S_298.15⁰ S_{T}^{0} - S_{298.15}^{0} ], were calculated from the heat capacity data in the temperature range of 80–380 K with an interval of 5 K. TG experiment showed that the pyrolysis of the compound was started at the temperature of 385 K and terminated at 510 K within one step.     

Synthesis of Novel <Emphasis Type="Italic">D</Emphasis>-<Emphasis Type="Italic">Seco</Emphasis>-Pregnenes

Summary. A new synthetic route was developed for the preparation of trans-3-hydroxy-16,17-seco-pregna-5,17(20)-dien-16-al, using Grob fragmentation as the key step. This seco-steroid contains a formyl group and an unsaturated side-chain in a sterically favourable position, and is therefore a promising starting material for the synthesis of novel condensed steroid heterocycles.Received March 22, 2003; accepted April 22, 2003 Published online September 25, 2003     

Conformations and properties of <Emphasis Type="Italic">O</Emphasis>-Alkyl-<Emphasis Type="Italic">S</Emphasis>-(2-<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-dialkylamino)-ethylmethylthiophosphonates

Conformers of the biologically active compounds CH₃P(O)(OR)(SCH₂CH₂NR ₂ ^′ ), where (I) R = i-C₄H₉, R′ = C₂H₅ and (II) R = C₂H₅, R′ = i-C₃H₇, are calculated within the AM1 level of theory. The elongated and twisted forms with maximum and minimum distances between a nitrogen atom and those of a phosphorus tetrahedron, respectively, and bearing a syn and anti oriented alkoxy group relative to a phosphoryl oxygen, are studied. It is found that the differences between the energy, electronic, and geometric parameters of these forms are apparent in differences between their properties, e.g., the ability to participate in complexation and protonation, reactions that to some extent simulate the interaction between a substance and a biological object.     

Synthesis of <Emphasis Type="Italic">ortho</Emphasis>-carboranyl derivatives of (<Emphasis Type="Italic">S</Emphasis>)-asparagine and (<Emphasis Type="Italic">S</Emphasis>)-glutamine

(S)-Asparagine and (S)-glutamine ortho-carboranyl derivatives with free amino and carboxy groups in the α-position were synthesized. By an example of N ^γ-(1,2-dicarba-closo-dodecarboran-3-yl)-(S)-glutamine it was demonstrated that the developed synthetic approach carboranyl derivatives of amino acids allowed the preparation of optically pure isomers.     

Synthesis of chiral glycolurils from (<Emphasis Type="Italic">S</Emphasis>)-(+)- and (<Emphasis Type="Italic">R</Emphasis>)-(-)-1-<Emphasis Type="Italic">sec</Emphasis>-butyl-3-methylurea

Chiral dialkyl- and tetraalkylglycolurils have been obtained using chiral (S)-(+)- and (R)-(-)-1-sec-butyl-3-methylurea as starting materials. The diastereomer (S)-(+)-2,6-di-sec-butyl-4,8-dimethyl-2,4,6,8-tetraazabicyclo[3.3.0]-octane-3,7-dione was separated into stereoisomers, for the higher melting of which the absolute configuration was determined as (S,S,S,S) by X-ray structural analysis.     

Synthesis of (<Emphasis Type="Italic">E</Emphasis>)-<Emphasis Type="Italic">N</Emphasis>-(3-alkoxy-4-acyloxyphenylmethylene)-<Emphasis Type="Italic">N</Emphasis>-(<Emphasis Type="Italic">e</Emphasis>-cyclohexyl)amines

Previously unknown E isomers of azomethines (Schiff bases) were synthesized from vanillal and vanillin esters by their reaction with cyclohexylamine.     

Synthesis of <Emphasis Type="Italic">N,N</Emphasis>-disubstituted (<Emphasis Type="Italic">Z</Emphasis>)-<Emphasis Type="Italic">O</Emphasis>-methylnicotinamide oximes

A number of (Z)-N,N-dialkyl- and (Z)-N-acyl-N-alkyl-O-methylnicotinamide oximes was synthesized. Their configuration was confirmed by the NOESY experiment. Evaluation of fungicidal activity of compounds obtained was performed.     

Quinine‐Derived Imidazolidin‐2‐imine Ligands: Synthesis,Coordination Chemistry,and Application in Catalytic Transfer Hydrogenation

Two new optically active bidentate N,N‐ligands, DMIQCI ( 3a ) and DMIQCD ( 3b ), containing a quinuclidine core and an imidazolidin‐2‐imine unit, were synthesized. The reaction of these ligands with [(η⁵‐C₅Me₅)RuCl]₄ afforded the brick‐red ruthenium(II) complexes [(η⁵‐C₅Me₅)Ru(DMIQCI)Cl] ( 4 ) and [(η⁵‐C₅Me₅)Ru(DMIQCD)Cl] ( 5 ), which were used as catalysts in the transfer hydrogenation of acetophenone in boiling 2‐propanol. The reactions of 3a and 3b with [(COD)PdCl₂] (COD = 1,5‐cycloocta‐diene) and with [(DME)NiBr₂] (DME = 1,2‐dimethoxyethane) afforded the square‐planar palladium(II) complexes [(DMIQCI)PdCl₂] ( 7 ) and [(DMIQCD)PdCl₂] ( 8 ) or the tetrahedral nickel(II) complexes [(DMIQCI)NiBr₂] ( 9 ) and [(DMIQCD)NiBr₂] ( 10 ), respectively. The X‐ray crystal structures of 4 , 7 , 9· THF, and 10 are reported.     

Screening and Immobilization <Emphasis Type="Italic">Burkholderia</Emphasis> sp. GXU56 Lipase for Enantioselective Resolution of (<Emphasis Type="Italic">R</Emphasis>,<Emphasis Type="Italic">S</Emphasis>)-Methyl Mandelate

Microorganisms producing lipase were isolated from soil and sewage samples and screened for enantioselective resolution of (R,S)-methyl mandelate to (R)-mandelic acid. A strain designated as GXU56 was obtained and identified as Burkholderia sp. Preparing immobilized GXU56 lipase by simple adsorption on octyl sepharose CL-4B, the optimum temperature was shifted from 40 °C (free lipase) to 50 °C (immobilized lipase), and the optimum pH was shifted from 8.0 (free lipase) to 7.2 (immobilized lipase). The immobilized enzyme displayed excellent stability in the pH range of 5.0–8.0, at the temperatures below 50 °C and in organic solvents compared with free enzyme. Enantioselectivity ratio for (R)-mandelic acid (E) was dramatically improved from 29.2 to more than 300 by applying immobilized lipase in the resolution of (R,S)-methyl mandelate. After five cycles of use of immobilized lipase, conversion and enantiomeric excess of (R)-mandelic acid were 34.5% and 98.5%, respectively, with enantioselectivity ratio for (R)-mandelic acid (E) of 230. Thus, octyl-sepharose-immobilized GXU56 lipase can be used as a bio-resolution reagent for producing (R)-mandelic acid.     

Synthetic Approaches to Physiologically Active Polycyclic Compounds: VI. Synthesis of 1-[(2<Emphasis Type="Italic">R</Emphasis>,3<Emphasis Type="Italic">S</Emphasis>)-<Emphasis Type="Italic">N</Emphasis>-Benzoyl-phenylisoseryloxy]-4,4-dimethyladamantane

A convenient procedure was proposed for the synthesis of 4,4-dimethyladamantan-1-ol from 2-adamantanone. Esterification of the product with protected amino acid gave 1-[(2R, 3S)-N-benzoylphenyl-isoseryloxy]-4,4-dimethyladamantane.     

Enantioselective microbial synthesis of (<Emphasis Type="Italic">S</Emphasis>)-7,8-difluoro-3,4-dihydro-3-methyl-2<Emphasis Type="Italic">H</Emphasis>-[1,4]benzoxazine

New strains of Rhodococcus erythropolis 25 and Microbacterium paraoxydans 20-11c actinobacteria were used to obtain (S)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (99.6% ee) by enantioselective microbial hydrolysis of the corresponding racemic N-acetyl derivative.     

Production of 6-<Emphasis Type="Italic">O</Emphasis>-<Emphasis Type="SmallCaps">l</Emphasis>-Ascorbyl Palmitate by Immobilized <Emphasis Type="Italic">Candida antarctica</Emphasis> Lipase B

l-ascorbyl palmitate (ASP) is an oil-soluble derivative of ascorbic acid which is used extensively in food, cosmetics industry, and medical hygiene. Enzymatic synthesis of ascorbyl palmitate in tert-butyl alcohol was carried out using indigenously immobilized lipase preparation PyCal with ascorbic acid and palmitic acid as starting material. The developed batch process under optimized reaction conditions resulted in conversion of 90% with relatively shorter reaction time of 6 h. Continuous process in packed bed reactor gave conversion of 50% with space time yield of 15.46 g/L/h which was found to be higher than the reported literature on enzymatic synthesis of ascorbyl palmitate. The immobilized lipase used in the present work showed good reusability. Characterization of formed ascorbyl palmitate was carried out by FTIR, MS/MS, H¹-NMR, and C¹³-NMR. The enzymatic process resulted in selective synthesis of 6-O-l-ascorbyl palmitate with purity of 98.6% and no side product formation. The use of underivatized starting materials, high space time yield of 15.46 g L^?1 h^?1, high recyclability of catalyst, and no by-product formation make the overall process highly efficient and clean in terms of energy consumption and waste generation, respectively. The optimized reaction parameters for ascorbyl palmitate synthesis in the present study can be used as a useful reference for industrial synthesis of fatty acid esters of ascorbic acid by enzymatic route.     

Pyrazoles and Pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>]pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrazines,I. Synthesis and Antimicrobial Activity

Summary. The synthesis of the title compounds was achieved using 1-phenyl-5-(pyrrol-1-yl)-1H-pyrazole-3-carboxylic acid azide as starting material. The latter compound was allowed to react with alcohols and amines to afford the corresponding carbamates and urea derivatives. Alkaline hydrolysis of the carbamates gave the corresponding amine, which was acylated and/or aroylated to give amide derivatives. These and the urea derivatives were subjected to cyclodehydration to give the title compounds. Antibacterial and antifungal activities were observed for several derivatives.     

Synthesis of pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

Synthesis of diethyl [(2<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>)-4-hydroxytetrahydrofuran-2-ylmethyl]phosphonate

A convenient method for the stereoselective synthesis of diethyl [(2S,4S)-4-hydroxytetrahydrofuran-2-ylmethyl]phosphonates was developed based on preparation of phophorylated glycol followed by its intramolecular cyclization and hydrogenation. It was shown that the nature of the hydrogenation products depends on the presence of water in the solvent.