Sugar-based Crown Ethers in Enantioselective Syntheses

A number of chiral macrocyclic compounds have been prepared that contain a monosaccharide-derived sub-unit. These sugar-based crown ethers were used as chiral phase transfer catalysts in a few asymmetric reactions. A few of them proved to be effective catalysts in Michael additions, a Darzens condensation and an epoxidation of α,β-enones. It was found that the type of the monosaccharide, the substituents on the sugar unit and on the nitrogen atom of the macroring have a significant influence on both the yield and the enantioselectivity

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 K < 2.3). 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) ~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 K = 6.15). 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. © 2014 Springer Science+Business Media Dordrecht

d-Idose-Based Monoaza-15-Crown-5 Lariat Ethers: Synthesis of an Elusive d-Hexose and Application of Derived Macrocycles in Enantioselective Syntheses

Carbohydrate-based macrocycles can be enantioselective catalysts in certain reactions. Previously, it was proven that the carbohydrate moiety could affect the catalytic activity of the monoaza-15-crown-5 type macrocycles derived from sugars. According to our experiments so far, the most effective enantioselective catalysts were the d-glucose- and the d-galactose-based crown ethers. To obtain more information about the effect of the carbohydrate unit, a rare monosaccharide, d-idose was incorporated into the monoaza-15-crown-5 structure. The key intermediates were methyl 4,6-O-benzylidene-α-d-idopyranoside and methyl 4,6-O-benzylidene-β-d-idopyranoside, which were synthesized from d-galactose. The efficiency of the idopyranoside-based crown compounds synthesized was investigated in asymmetric phase transfer reactions. In liquid-liquid biphasic reactions the highest enantioselectivity was 81% ee, while in solid-liquid phase systems the highest asymmetric induction was 67% ee. It was observed that the enantiodiscrimination was strongly dependent on the configuration of the anomeric center, on the side arm of the nitrogen, and on the structure of the substrate

Crown ether derived from D-glucose as an efficient phase-transfer catalyst for the enantioselective Michael addition of malonates to enones

A monoaza-15-crown-5 lariat ether derived from D-glucose (1) has been applied as chiral phase-transfer catalyst in the Michael addition of diethyl, dimethyl, diisopropyl and dibenzyl malonates to enones under mild conditions to afford the adducts in good to excellent enantioselectivities. In the reaction of diethyl malonate with substituted trans-chalcone, the adducts formed in enantioselectivities up to 89% ee. Among the reactions of substituted diethyl malonates, that of diethyl acetoxymalonate gave the best results (96% ee). The effect of the substituents of the chalcone was also investigated in reaction with diethyl acetoxymalonate. Among the chalcones substituted on the β side, the para-substituted compounds resulted in the highest enantioselectivities (88-97% ee). The substituents on the α-side of chalcone caused a decrease in the enantioselectivity, as compared to the unsubstituted case. The adducts having furyl or thiophenyl substituents were formed with >99% ee. The glucose-based catalyst also proved to be effective in the cases of diisopropyl and dibenzyl acetoxymalonates (including ee-s up to 99% ee). The reactions of diethyl acetoxymalonate with cyclic enones gave the corresponding Michael adducts in enantioselectivities up to 83%. The absolute configuration of one of the new Michael adducts was determined by CD spectroscopy

Asymmetric addition of P-H compounds to unsaturated carbonyl derivatives

Michael addition of P-H compounds, such as phosphanes, phosphane oxides and phosphonates, is a practical tool to form P-C bonds. The stereochemistry of the newly formed compounds can be influenced either by using chiral starting materials or chiral catalysts. Since the former method is limited to the readily available opticallyactive derivatives, catalytic options are more common. Enantioenriched P-C compounds can have biological activity; therefore, they are pharmaceutically valuable molecules. In this paper, an overview is provided on the conjugate addition of P-H compounds according to the type of the phosphorus derivatives