Asymmetric Weitz–Scheffer epoxidation of conformationally flexible and fixed enones with sterically demanding hydroperoxides mediated by optically active phase-transfer catalysts

The asymmetric Weitz–Scheffer epoxidation of α,β-enones 1a–d with hydroperoxides 2 and mediated by cinchonine- and cinchonidine-derived phase-transfer catalysts (PTCs) 3 affords the optically active epoxides 4 with moderate to very good e.e.s and in near quantitative yields. For the conformationally flexible enone 1b, the enantioselectivity decreases with more sterically demanding tertiary hydroperoxides, while an opposite trend is observed for the rigid s-cis-enone 1. With the bulky cumyl hydroperoxide 2c and the PTC 3c, the enone 1 was converted to the epoxide 4c with the highest enantioselectivity (95% e.e.) so far observed for PTC-catalyzed epoxidations using hydroperoxides as oxygen sources.     

A highly efficient kinetic resolution of γ- and β- trimethylsilyl secondary allylic alcohols by the sharpless asymmetric epoxidation

Kinetic resolution of γ- and β-trimethylsilyl secondary allylic alcohols proceeds with very large and synthetically satisfactory rate differences for the two enantiomers, respectively, thus providing a convenient and widely applicable method for preparation of various kinds of homochiral compounds.     

Influence of hydroperoxides on the enantioselectivity of metal-catalyzed asymmetric Baeyer–Villiger oxidation and epoxidation with chiral ligands

Chiral hydroperoxides have a significant influence on the enantioselectivity of the metal-catalyzed asymmetric Baeyer–Villiger oxidation of cyclic ketones and the epoxidation of allylic alcohols, when chiral ligands are employed. If both the ligand and the hydroperoxide are enantiopure, the ligand determines the formation of the preferred product enantiomer in both reactions.     

Process-scale preparation of enantiomerically pure γ-lactones by asymmetric hydrogenation of γ-ketoesters and comparative tests of the sensory properties of some antipodes

A reliable methodology, applicable on a process-scale level, for producing enantiomerically pure chiral γ-lactones by enantioselective hydrogenation of γ-ketoesters, followed by cyclisation of the resulting γ-hydroxyesters, has been developed. The multi-step procedure was transformed into a one-pot reaction. A very efficient chiral Ru-complex, based on the biheteroaromatic diphosphine ligand tetraMe-BITIOP, was developed as a catalyst, capable of coupling fast kinetics with high stereoselection levels. Its structure was fully elucidated through ³¹P NMR, EPR and X-ray single-crystal analyses. The optimal experimental conditions are as follows: hydrogen pressure = 30 psi, S/C ratio = 2000, 30% in weight substrate concentration. Yields are quantitative and enantiomeric excesses in the range 98–99.9%. Sensorial tests on the antipodes of two γ-lactones demonstrated the very different properties of the enantiomers.     

Comparison of Ta–MCM-41 and Ti–MCM-41 as catalysts for the enantioselective epoxidation of styrene with TBHP

Chiral Ti–MCM-41 and Ta–MCM-41 catalysts have been prepared by grafting of Ti(OⁱPr)₄ and Ta(OEt)₅ and the modification with R-(+)-diethyl l-tartrate or R-(+)-diisopropyl l-tartrate. In general, the solid catalysts are more active and selective than their homogeneous counterparts in the epoxidation of styrene with tert-butyl hydroperoxide. The enantioselectivities depend on both the nature of the chiral ligand and the calcination temperature of the support, as it is supposed this controls the type of surface species that are formed. The best result of 71% ee is obtained with DIPT–Ta–MCM₅₅₀ and is the first example of the use of a Ta catalyst for the enantioselective epoxidation of unfunctionalized alkenes. Nonetheless, the recovered Ta catalysts are less active and selective.     

Sharpless asymmetric dihydroxylation as the key step in the enantioselective synthesis of spirocyclic σ1 receptor ligands

The enantioselective synthesis of fluorinated spirocyclic σ₁ ligands involved three key steps: (1) the Sharpless asymmetric dihydroxylation of 2-bromostyrene 5 provided enantiomerically pure diols (R)-6 and (S)-6 establishing the stereogenic center; (2) the intramolecular opening of the oxirane ring of (R)-11 and (S)-11, which occurred with excellent regioselectivity and complete inversion of configuration giving access to enantiomerically pure alcohols (S)-7a and (R)-7a; (3) the treatment of alcohols (S)-7b and (R)-7b with DAST, which led to the fluoromethyl derivatives (S)-1 and (R)-1 without racemization. X-ray crystal structure analysis of the tosylate (R)-13 confirmed the absolute configuration of the spirocyclic compounds as well as the enantioselectivity during the Sharpless asymmetric dihydroxylation of 5. The (S)-configured fluoromethyl derivative (S)-1 revealed a high σ₁ affinity (K_i = 1.8 nM), high eudismic ratio (factor 8) and high selectivity over the σ₂ subtype (667-fold).     

Preparation of pure and Sm-doped Na0.5Bi0.5TiO3 nanosized powders by sol–gel method and their electrical properties

Research on Chemical Intermediates - The sol–gel method was applied to synthesize Na0.5Bi0.5TiO3 (NBT) sols and ceramic powders by using glycol as solvent and the optimized condition was...     

Dipyridyl β-diketonate complexes and their use as metalloligands in the formation of mixed-metal coordination networks

The iron(III) and aluminium(III) complexes of 1,3-di(4-pyridyl)propane-1,3-dionato (dppd) and 1,3-di(3-pyridyl)propane-1,3-dionato (dmppd), [Fe(dppd)(3)] 1, [Fe(dmppd)(3)] 2, [Al(dppd)(3)] 3 and [Al(dmppd)(3)] 4 have been prepared. These complexes adopt molecular structures in which the metal centres contain distorted octahedral geometries. In contrast, the copper(II) and zinc(II) complexes [Cu(dppd)(2)] 5 and [Zn(dmppd)(2)] 6 both form polymeric structures in which coordination of the pyridyl groups into the axial positions of neighbouring metal centres links discrete square-planar complexes into two-dimensional networks. The europium complex [Eu(dmppd)(2)(H(2)O)(4)]Cl·2EtOH·0.5H(2)O 7 forms a structure containing discrete cations that are linked into sheets through hydrogen bonds, whereas the lanthanum complex [La(dmppd)(3)(H(2)O)]·2H(2)O 8 adopts a one-dimensional network structure, connected into sheets by hydrogen bonds. The iron complexes 1 and 2 act as metalloligands in reactions with silver(I) salts, with the nature of the product depending on the counter-ions present. Thus, the reaction between 1 and AgBF(4) gave [AgFe(dppd)(3)]BF(4)·DMSO 9, in which the silver centres link the metalloligands into discrete nanotubes, whereas reactions with AgPF(6) and AgSbF(6) gave [AgFe(dppd)(3)]PF(6)·3.28DMSO 10 and [AgFe(dppd)(3)]SbF(6)·1.25DMSO 11, in which the metalloligands are linked into sheets. In all three cases, only four of the six pyridyl groups present on the metalloligands are coordinated. The reaction between 2 and AgNO(3) gave [Ag(2)Fe(dmppd)(3)(ONO(2))]NO(3)·MeCN·CH(2)Cl(2)12. Compound 12 adopts a layer structure in which all pyridyl groups are coordinated to silver centres and, in addition, a nitrate ion bridges between two silver centres. A similar structure is adopted by [Ag(2)Fe(dmppd)(3)(O(2)CCF(3))]CF(3)CO(2)·2MeCN·0.25CH(2)Cl(2)13, with a bridging trifluoroacetate ion playing the same role as the nitrate ion in 12.     

Synthesis and characterization of hydrophilic theophylline base compounds and their use as ligands in the microwave assisted Suzuki–Miyaura couplings of halopyridines in water

Xanthine derivatives, caffeine (L1), theobromine (L2), theophylline (L3), 7-(β-hydroxyethyltheophylline) (L4), (7-(2,3-dihydroxypropyl)theophylline) (L5), and theophylline 7-acetic acid (L6) and the acetylated derivatives of the later three (L7–L9) were employed as ligands for the in situ palladium catalyzed Suzuki–Miyaura cross couplings of a series of halogenated pyridines. Optimized conditions were found where the diacetylated ligand (L8) was determined to be the best for this process, producing good to excellent yields in the couplings of halogenated anilines with phenylboronic acid under mild reaction conditions in water using microwave irradiation.     

Methods for the synthesis of chiral sulfur heterocycles and their application in the asymmetric Baylis–Hillman reactions

Enantiomerically pure (2S,6S)-2,6-diphenyltetrahydro-2H-thiopyran, (2S)-2-phenyltetrahydro thiophene, and (2S)-2-phenyltetrahydro-2H-thiopyran were prepared in 70–72% yields and with 86–99% ee via cyclization of the corresponding dimesylate in an S_N2 cyclization reaction using sodium sulfide nonahydrate. The results on the application of various chiral sulfides in asymmetric Baylis–Hillman reactions are also described.     

Synthesis and asymmetric alkylation of glucose-derived bicyclic oxazinones: An evaluation of their use as “chiral glycines”

We have prepared structurally novel bicyclic oxazinones based on D-glucopyranose. The lithium enolates of these compounds undergo highly diastereoselective alkylation reactions with reactive alkyl halides, in modest yields. Use of the phosphazene P4 base enhances the yields of these processes, suggesting that metal enolate aggregation is at least partly responsible for the depressed yields. The stereochemistry of the products has been unequivocally ascertained by nOe measurements and ab initio calculations.     

Synthesis of imine–amine type of chiral ligands and their application in the asymmetric cyclopropanation of olefins with diazoacetates

Novel chiral ligands 1, which possess both imine and amine moieties, were prepared from readily available homochiral materials. Copper complexes of 1 were prepared in situ and used in the asymmetric cyclopropanation of olefins with alkyl diazoacetates to give cyclopropanecarboxylates, inducing e.e. values of up to 87%. The size of the chelate ring in the copper complexes influenced the enantioselectivity of the reaction.     

Preparation of polyaniline–tin dioxide composites and their application in methanol electro-oxidation

Polyaniline–tin dioxide (PANI-SnO₂) composites were prepared by chemical polymerization method, and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Due to the good stability in diluted acidic solution, PANI-SnO₂ composites were selected as the catalyst support and second catalyst for methanol electro-oxidation. The electrocatalytic properties of the PANI-SnO₂ supported Pt catalyst (Pt/PANI-SnO₂) for methanol oxidation have been investigated by cyclic voltammetry, chronoamperometry, and chronopotentiometry. Under the same loading mass of Pt, the Pt/PANI-SnO₂ catalyst shows higher electrocatalytic activity towards methanol electro-oxidation than Pt/SnO₂ catalyst.     

Synthesis and computation of diastereomeric phenanthroline–quinine ligands and their application in asymmetric Henry reaction

A class of chiral ligands has been developed by combining phenanthroline with quinine in a one-step method that does not require resolution. The synthesized three ligands were then coordinated with Cu^(II) and the performance of the resultant chiral catalysts in the asymmetric Henry reaction was evaluated. Moderate to good yields (up to 86%) with high enantioselectivities (up to 99% ee) were observed in the reactions catalyzed by one of the three catalysts. Theoretical calculations were performed to analyze the catalytic activities of the different Cu^(II)-ligand catalysts. Three different ligands were investigated and one ligand was found to adopt an unexpected five-coordinated mode; the second coordinated with two nitrogen atoms of phenanthroline to give a complex, which activated both substrates of Henry reaction; the third was unable to form a complex with Cu^(II).     

First example of a silica gel-supported optically active Mn(III)–salen complex as a heterogeneous asymmetric catalyst in the epoxidation of olefins

An optically active Mn(III)–salen complex was supported on silica gel materials: the insoluble systems obtained were employed as catalysts in the asymmetric epoxidation of some aromatic olefins. Enantiomeric excess values up to 58% were obtained.     

Synthesis of novel β-amino alcohols and their application in the catalytic asymmetric sulfoxidation of sulfides

Novel chiral norephedrine-based β-amino alcohol ligands containing a thiophene ring were prepared from norephedrine and substituted furan carbaldehydes (methyl- or ethyl-substituted) and used in combination with VO(acac)₂ for the asymmetric oxidation of aryl methyl sulfides using H₂O₂ as an oxidant. Amino alcohol derived Schiff bases 4,5a–b gave higher enantiomeric excesses than amino alcohol-derived reduced Schiff based ligands 6,7a–b. Of these chiral ligands, (1S,2R)-5b and (1S,2R)-7b gave high yields (90%) with moderate to high enantioselectivities (78%, 96% ee, respectively). The oxidation of other aryl methyl sulfides with (1S,2R)-5b and (1S,2R)-7b as ligands afforded the corresponding sulfoxides in 60–89% yields and with 92–99% ee.     

An l-proline-based β-amino tertiary thiol: synthesis and use as a catalyst in the enantioselective addition of diethylzinc to aldehydes

Two independent routes for the synthesis of the novel β-amino tertiary thiol 1 have been developed. Utilisation of this thiol in the enantioselective addition of diethylzinc to aldehydes provided (R)-secondary alcohols in ees of up to 64%.     

Synthesis of enantiopure β-azidoalcohols from their ketoazides by reduction with NaBH4 in the presence of alumina and in situ lipase resolution

An enantioselective synthesis of chiral β-azidoalcohols via the reduction of the corresponding ketoazides with NaBH₄ in the presence of moist aluminium oxide followed by an in situ lipase-mediated resolution is described. The efficiency of various lipases and the effect of solvents have also been studied for this method. The excellent results obtained under mild reaction conditions, indicates its applicability and importance over classical methods previously reported.     

Chiral nickel(II) complexes in the preparation of 11C- and 18F-labelled enantiomerically pure α-amino acids

Positron emission tomography (PET) utilises positron emitting radiopharmaceuticals in the study of metabolic and physiological processes. FDG-PET is a useful technique for tumour detection; however FDG has disadvantages. The incorporation of labelled amino acids into brain tumours and into some other organs with high physiological consumption of glucose is a superior diagnostic method due to its much higher selectivity compared to FDG. A Ni(II) complex with a Schiff base of BPB and glycine was one of the first glycine synthons used for asymmetric synthesis of carbon-11 and fluorine-18 labelled α-amino acids. A similar complex was employed for routine preparation of [(18)F]FET. Physico-chemical investigations allowed us to design modified complexes with much stronger stereodiscriminative power including stereospecific ones. Chiral nickel complexes are also used for the preparation of tailored amino acids for the incorporation into peptides followed by labelling the peptides with fluorine-18 labelled "click" reagents. This review covers PET applications of Ni(II) complexes of Schiff base of BPB and α-amino acids from 1989 to date.     

Preparation of polymeric modifier-attached graphene-supported bimetallic Pt–Pd nanocomposites,and their electrochemical properties as electro-catalysts

Graphene-supported bimetallic nanocomposites were synthesized by a modified sodium borohydride reduction method. Poly(diallyldimethylammonium chloride) (PDDA) was used as modifier for good dispersion and higher metal alloy content. The micro-structure and dispersive properties of the electro-catalysts were determined by X-ray diffraction, Fourier-transform-infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. The electrochemical properties of the Pt–Pd electro-catalysts were studied by cyclic voltammetry. This analysis confirmed that functional groups on the graphene oxide (GO) sheet were chemically bonded to the PDDA layer. The average particle diameter of Pt–Pd_{1 to 0.5}–PDDA–reduced graphene oxide (RGO) was found to be 2.4 ± 0.4 nm which is the smallest platinum metal particle size among Pt–Pd–PDDA–RGO electro-catalysts. The electrochemically active surface area was studied and the activity was found to be enhanced by use of the polymeric modifier.