Zsolt Rapi

Synthesis of ribo-hexopyranoside- and altrose-based azacrown ethers and their application in an asymmetric Michael addition

The synthesis of four new ribo-hexopyranoside-based chiral lariat ethers of monoaza-15-crown-5 type and two altropyranoside-based crown ethers were elaborated. Our syntheses utilized the regioselective ring opening of the oxiran moiety of the 2,3-anhydro sugars by nucleophilic reagents to afford the key intermediates. The reaction of methyl-2,3-anhydro-4,6-O-benzylidene-α-D-mannopyranoside with ethanolamine is especially of interest to afford a 3-substituted altropyranoside. One of the ribo-hexopyranoside-based lariat ethers with a 4-methoxyphenyl substituent induced an enantioselectivity of 80% when used as catalyst in the Michael addition of diethyl acetamidomalonate to trans-β-nitrostyrene under phase transfer catalytic conditions.

Synthesis of an Aza Chiral Crown Ether Grafted to Nanofibrous Silica Support and Application in Asymmetric Michael Addition

We report on the synthesis of a new, supported phase transfer catalyst and its asymmetric induction. An inorganic-polymer-supported chiral crown ether was prepared by the reaction between an optically active macrocycle deriving from methyl-α-d-glucopyranoside and silica nanofibres. The inorganic carrier of the catalyst has high specific surface area due to its nanofibrous structure, which is favourable for heterogeneous catalytic reactions. SiO2 fibres were electrospun from silica sol which was prepared via sol–gel reactions from tetraethylorthosilicate. The asymmetric Michael reaction of diethyl acetamidomalonate and β-nitrostyrene was selected for the comparison of the performance of various glucopyranoside-based macrocycles. The asymmetric inductions of macrocycles provided 20–99xa0% enantiomeric excess. A triethoxysilyl derivative was prepared from the highly enantioselective macrocycle in order to immobilize it on the surface of the silica nanofibres. The supported glucose based monoaza-15-crown-5 type macrocycle was characterized by X-ray photoelectron spectroscopy and compared with non-supported native crown ethers in the asymmetric Michael addition. The immobilized phase-transfer catalyst generated high enantiomeric excess (82xa0%) in spite of the fact that it was used in a three-phase reaction.

Synthesis of α-D-galactose-based azacrown ethers and their application as enantioselective catalysts in Michael reactions

New chiral monoaza-15-crown-5 type macrocycles annelated to methyl 4,6-O-benzylidene-α-D-galactopyranoside have been synthesized. These crown ethers proved to be efficient catalysts in a few asymmetric reactions under mild phase transfer catalytic conditions. Michael adducts were formed with good to excellent enantioselectivities, so the addition of diethyl acetamidomalonate to β-nitrostyrene took place with up to 92% ee, while the reaction of diethyl acetoxymalonate with chalcones proceeded with up to 99% ee. Using diethyl bromomalonate as the nucleophile, the chiral cyclopropane derivatives were formed in up to 99% ee with the addition to chalcone, in up to 78% ee in the reaction with benzylidene malononitrile, and in up to 76% ee in the reaction with 2-benzylidene-1,3-diphenyl-1,3-propanedione applying α-D-galactoside-based crown ethers as the catalysts. In the Michael addition, the substituents of the chalcone had a considerable impact on the outcome of the reactions. Quantum chemical calculations have also been employed to evaluate the origin of the stereoselectivities.

Synthesis and recognition properties of α- d -glucose-based fluorescent crown ethers incorporating an acridine unit

Two new chiral glucopyranoside-based crown ethers incorporating acridine fluorescent signalling units, 15-membered ligand 1 and 21-membered ligand 2 were synthesized. Their complexation properties toward alkali and alkali earth metal ions, and their enantioselectivity towards chiral ammonium salts were studied by absorption and fluorescence spectroscopic experiments. Macrocycle 1 formed 1:1 complexes with all the metal ions selected and the stability constants were low (lg Kxa0<xa02.3). The cavity-size of 2 allowed only the complexaton of organic ammonium ions. Crown 2 showed chiral discrimination in case of all the four ammonium salts used as model guest compounds; the highest enantioselectivity (K(R)/K(S)xa0~3) was observed for the enantiomers of phenylethyl ammonium perchlorate. Ligand 2 forms much more stable complexes with metal ions; the highest stability constant was obtained for the Ca2+ complex (lg Kxa0=xa06.15). The coordination of metal ions by ligand 2 was accompanied by marked fluorescence enhancement, whereas the binding of ammonium ions by the same species resulted in significant fluorescence quenching.

Diethyl (cyanofluoromethyl)phosphonate: Application in catalytic enantioselective Michael additions

GRAPHICAL ABSTRACT ABSTRACT Three types of chiral catalysts: a chincona-based squaramide, TADDOL and a group of sugar-based crown ethers were applied to the asymmetric Michael addition of diethyl (cyanofluoromethyl)phosphonate to diverse Michael acceptors. Two of the crown ether catalysts resulted in high yields and enantioselectivities with trans-β-nitostyrene as in case of the chincona-based squaramide catalyst the yield was low with high enantioselectivity. TADDOL proved to be active, but less selective in the Michael addition.

Synthesis of alkyl α- and β-d-glucopyranoside-based chiral crown ethers and their application as enantioselective phase-transfer catalysts

Chiral monoaza-15-crown-5-type lariat ethers annelated to alkyl 4,6-O-benzylidene-α- and β-d-glucopyranosides have been synthesized. These macrocycles generated significant asymmetric induction as phase-transfer catalysts in a few two-phase reactions. The catalytic effect of the lariat ethers with methoxy, ethoxy, and i-propoxy substituents on C-1 of the sugar unit in both α and β positions was compared. In liquid–liquid two-phase reactions, the nature and position of the substituents did not have much effect. The α-anomers were somewhat more efficient in terms of enantioselectivity than the β forms. In asymmetric Darzens condensations, in the epoxidation of trans-chalcone, in the Michael addition of β-nitrostyrene and diethyl acetamidomalonate, and in the reaction of 2-benzylidene-1,3-indandione with diethyl bromomalonate, maximum enantioselectivities of 73, 94, 78, and 72%, respectively, were obtained in presence of glucopyranoside-based lariat ethers as catalysts.

Synthesis of d-mannitol-based crown ethers and their application as catalyst in asymmetric phase transfer reactions

A few new d-mannitol-based monoaza-15-crown-5 type chiral lariat ethers and 18-crown-6 type macrocycles were synthesized. These crown compounds were used as phase transfer catalysts in asymmetric Michael addititons and in a Darzens condensation under mild conditions to afford the corresponding products in a few cases in good to excellent enantioselectivities. In the Michael addition of diethyl acetoxymalonate to trans-chalcone, in the addition of diethyl acetamidomalonate to ß-nitrostyrene, in the reaction of diethyl bromomalonate with benzylidene malononitriles, in the cyclopropanation reaction of diethyl bromomalonate and 2-benzylidene-1,3-indandione, and in the Darzens condensation of α-chloroacetophenone with benzaldehyde, maximum enantioselectivities of 39%, 65%, 99%, 56%, and 62%, respectively, were obtained in the presence of the d-mannitol-based macrocycles as the catalysts.

Synthesis of l-threitol-based crown ethers and their application as enantioselective phase transfer catalyst in Michael additions

A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit were synthesized starting from diethyl l-tartrate. These macrocycles were used as phase transfer catalysts in asymmetric Michael addition reactions under mild conditions to afford the adducts in a few cases in good to excellent enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the reaction of diethyl acetamidomalonate with β-nitrostyrene resulted in the chiral Michael adducts in good enantioselectivities (90% and 95%, respectively). The substituents of chalcone had a significant impact on the yield and enantioselectivity in the reaction of diethyl acetoxymalonate. The highest enantiomeric excess (ee) values (99% ee) were measured in the case of 4-chloro- and 4-methoxychalcone. The phase transfer catalyzed cyclopropanation reaction of chalcone and benzylidene-malononitriles using diethyl bromomalonate as the nucleophile (MIRC reaction) was also developed. The corresponding chiral cyclopropane diesters were obtained in moderate to good (up to 99%) enantioselectivities in the presence of the threitol-based crown ethers.

Syntheses and complexing ability of α-d-gluco- and α-d-xylofuranoside-based lariat ethers

Chiral monoaza-15-crown-5 lariat ethers attached to a 1,2-O-isopropylidene-α-d-glucofuranoside unit (10–13), monoaza-16-crown-5 lariat ethers fused to 1,2-O-isopropylidene-α-d-glucofuranoside- (18) and to 1,2-O-isopropylidene-α-d-xylofuranoside units (23 and 24) have been synthesized. The alkali metal- and ammonium picrate extracting ability of these macrocycles was investigated in dichloromethane–water system. In general, the 15-membered macrocycles (10–13) showed, for almost all cations, a more considerable extracting ability, than the 16-membered lariat ethers (18, 23 and 24). Plasticized PVC membrane electrodes (ISEs) were prepared from the α-d-glucofuranoside-based triphenylmetyl (trityl) ether derivative (18), and its potentiometric selectivities and complex formation constants were determined with the segmented sandwich membrane method. Furthermore, the binding affinities of ionophores to different metal ions were also measured by competitive ESI–MS experiments. One of the 1,2-O-isopropylidene-α-d-glucofuranoside-based lariat ethers (13) exhibited a high selectivity for silver ion (Ag+).

Enantioselective synthesis of substituted α-aminophosphonates catalysed by D-glucose-based crown ethers: pursuit of the origin of stereoselectivity

Several monoaza-15-crown-5 type macrocycles annelated to phenyl-β-D-glucopyranoside were applied as chiral catalysts in enantioselective Michael addition of an N-protected aminomethylenephosphonate onto acrylic acid derivatives and trans-β-nitrostyrene. Among these crown ethers, three are new. Michael adducts were formed with good to excellent enantio- and diastereoselectivities. Combined MM and QM calculations have revealed that suitable side arms on the crown ether beneficially affect the position of the central sodium cation, which in turn helps enhance the stereocontrol by allowing a closer contact between substrate and catalyst.