Synthesis of novel spiro imidazolium salts as chiral ionic liquids

A library of 13 novel chiral spiro imidazolium salts has been synthesized. The effects of N-substituents and counteranions on the melting point of spiro bis(imidazolium) salts are studied in efforts toward the development of room temperature chiral ionic liquids.     

(±)-Rubioncolin D,a pair of enantiomeric naphthohydroquinone dimers from Rubia oncotricha

A pair of novel enantiomeric naphthohydroquinone dimers with an unprecedented spiro[4.5] carbon core, (±)-rubioncolin D (1), were isolated from Rubia oncotricha. The racemic mixture of 1 was separated by chiral column chromatography. Their structures and stereochemistry were elucidated by extensive spectroscopic analysis and electronic circular dichroism calculation. Both compounds (+)-1 and (?)-1 exhibit weak cytotoxicities against A549, SGC-7901 or HeLa cancer cell lines.     

Synthesis and applications of (1R,5S,6S)-6-(2,2-dimethylpropanamido)spiro[4.4]nonan-1-ol as a chiral auxiliary in Diels–Alder reactions

A short asymmetric synthesis of (1R,5S,6S)-6-(2,2-dimethylpropanamido)spiro[4.4]nonan-1-ol 7 is described along with its application as a chiral auxiliary in various Diels–Alder reactions. The enantioselectivity of the Diels–Alder adducts ranged from 86–98% ee. The Diels–Alder adducts were easily removed from the chiral auxiliary and the latter was recyclized. The absolute and relative stereochemistry of 7 was determined from an X-ray crystal structure of the p-bromobenzoate derivative of 7.     

Synthesis of enantiomerically pure telluronium salts by the reaction of chiral tellurides with alkyl halides

Enantiomerically pure benzyl and ethoxycarbonylmethyl telluronium salts 4, using 2-exo-hydroxy-10-bornyl group as a chiral ligand, have been prepared in good yield and diastereoselectivity by the reaction of chiral tellurides 3 with alkyl halides. A structure with R_Te absolute configuration at the tellurium atom was confirmed by an X-ray analysis of 4a.     

Novel C2-symmetric chiral 18-crown-6 derivatives with two aromatic sidearms as chiral NMR discriminating agents

Novel C₂-symmetric chiral 18-crown-6 derivatives with two aromatic sidearms 2-4 were prepared, and their enantiomeric recognition abilities as chiral NMR discriminating agents towards primary ammonium salts were examined. Among these chiral crown ethers, the most effective enantiomeric discrimination of racemic ammonium salts in the ¹H NMR spectra was attained by the derivative with two pyrenylmethyl sidearms.     

Synthesis of benzannulated spiroacetals using chiral gold–phosphine complexes and chiral anions

The development of an asymmetric gold-catalysed dihydroalkoxylation strategy for the synthesis of the 3′H-spiro[chroman-2,1′-isobenzofuran] spiroacetal ring system 5 is described. Spiroacetal was generated in up to 87:13 enantiomeric ratio using chiral gold–phosphine complexes and chiral silver phosphate Ag(S)-TRIP.     

Highly enantioselective Michael/cyclization tandem reaction between dimedone and isatylidene malononitriles

A highly enantioselective Michael/cyclization tandem reaction between dimedone and isatylidene malononitriles has been developed. With 5?mol% of bifunctional organocatalyst C15, chiral spiro[2-amino-4H-pyran-oxindole] derivatives were obtained in excellent yields (97–99%) with excellent enantioselectivities (up to?>?99% ee).     

Chiral lariat ethers as membrane carriers for chiral amino acids and their sodium and potassium salts

Four chiral lariat ethers 8–11 containing a (p-methoxyphenoxy) methyl side arm were used for chiral discrimination of amino acids in their zwitterionic form or as potassium and sodium salts in transport across a bulk chloroform membrane with satisfactory selectivity. The carriers that were employed exhibited different transport selectivity relative to the amino acids and their salts under study. The d/l selectivity strongly depends on the amino acids or their salts, and in some cases reverse selectivity has been obtained. The best selectivity was obtained in the case of tyrosine and its potassium salts for all carriers. The transport rates of amino acids and their salts were found to be controlled by factors such as the structure of the carriers and amino acids or their salts. Among these factors, it was also found that the side arm of the lariat ethers plays an important role in the transport process. As a consequence, the main goal of our investigation was to separate the chiral amino acids through liquid membranes.     

Highly enantioselective 1,3-dipolar cycloaddition of imino esters with benzofuranone derivatives catalyzed by thiourea−quaternary ammonium salt

Highly enantioselective 1, 3-dipolar cycloaddition of 2-arylidene-benzofuran- 3(2H)-ones with imino esters catalyzed by thiourea?quaternary ammonium salts has been developed. This reaction provides efficient construction of a range of chiral spiro[benzofuran-2,3′-pyrrolidine] in high yields (up to 99%) and with good enantioselectivities (up to 99% ee) under mild conditions.     

Synthesis and chiral recognition ability of O-phenyl ethylphosphonothioic acid with a conformationally flexible phenoxy group for CH/π interaction

Enantiopure O-phenyl ethylphosphonothioic acid 1 was easily obtained by the enantioseparation of racemic 1, which was prepared from commercially available phosphorothioic trichloride in four steps. Enantiopure 1 was found to show an excellent chiral recognition ability for various 1-arylethylamine derivatives during the diastereomeric salt formation. In particular, enantiopure 1 was able to recognize the chirality of o- and m-substituted 1-arylethylamine derivatives, of which the chirality is generally difficult to establish by conventional resolving agents. X-ray crystallographic analyses of the less-soluble diastereomeric salts revealed that the conformation of the phenoxy group in enantiopure 1 could change in the diastereomeric salt crystals and that the excellent chiral recognition ability of enantiopure 1 resulted from the effective CH/π interaction of the phenoxy phenyl group.     

Palladium-catalyzed asymmetric umpolung allylation of imines with allylic alcohols

A palladium-catalyzed asymmetric umpolung allylation reaction of imines with allylic alcohols has been developed. In the presence of chiral spiro phosphoramidite ligand 4, the allylation was accomplished with high yields and good enantioselectivities. The use of highly stable and easily available allylic alcohols instead of allylic metal reagents facilitated the preparation of chiral homoallylic amines.     

Asymmetric synthesis of tetracyclic substructures of Strychnos indole alkaloids

The addition of the enolate of methyl 1-methyl-2-indoleacetate 1 and lithium 2-(lithiomethyl)indole-1-carboxylate 5 to pyridines and N-alkylpyridinium salts bearing a chiral auxiliary at the 3-position (tolylsulfinyl, acyl iron complexes, bornane-10,2-sultam), with subsequent acid cyclization of the resulting dihydropyridines, is investigated.     

Total synthesis of myxol and deoxymyxol stereoisomers and their application to determining the absolute configurations of the natural products

The total synthesis of myxol stereoisomers 1a,b and deoxymyxol (plectaniaxanthin) stereoisomers 2a,b was accomplished by Wittig reaction of (S)- and (R)-C₁₀-phosphonium salts 8a,b bearing a silyl-protected 1,2-dihydroxy-ψ end group with C₃₀-apocarotenals 6 and 7. The phosphonium salts 8a,b were derived from aldehydes 11a,b possessing a cyclopentylidene ketal moiety, prepared via Sharpless asymmetric epoxidation of allylic alcohol 12 followed by regioselective cleavage of the oxirane ring. We established an analytical HPLC method using a chiral column to separate stereoisomers 1a,b and 2a,b and thus determined the absolute configurations of the natural products. The HPLC analyses established that both myxol and deoxymyxol isolated from bacteria have the 2′S-configuration.     

Enantioselective glyoxylate-ene reaction using a novel spiro bis(isoxazoline) ligand in copper catalysis

Novel chiral spiro bis(isoxazoline) ligands 3 and 4 are synthesized from an optically active olefin. The Cu(II)-spiro bis(isoxazoline) complex prepared in situ from Cu(OTf)₂ and 3 promoted the glyoxylate-ene reaction in high yield and moderate enantioselectivity (up to 70%).     

Total synthesis of (−)-jaspine B and its 4-epi-analogue from d-xylose

The total synthesis of the HCl salts of (−)-jaspine B ent-1 and its 4-epi-congener ent-4 was accomplished starting from the common template 13 derived from d-xylose. The cornerstone of our synthesis was [3,3]-heterosigmatropic rearrangements, which effectively provided scaffolds with a chiral amino group. A subsequent Wittig olefination installed a C₁₄ alkyl side chain and acid-mediated ring-closing reaction established the tetrahydrofuran core.     

Design and synthesis of novel chiral spiro ionic liquids

[reaction: see text] Novel chiral imidazolium salts have been synthesized as examples of chiral ionic liquids with a spiro skeleton. Effects of N-substituents and counteranions on the melting point of spiro imidazolium salts and their chiral discrimination abilities are described.     

Absolute structure of shoreaketone: a rotational isomeric resveratrol tetramer in Dipterocarpaceaeous plants

A rotational isomeric shoreaketone (1), identified as a skeletal member of resveratrol tetramers, was isolated from three species of Dipterocarpaceaeous plants: Shorea uliginosa, Shorea hemsleyana, and Vateria indica. The structure was elucidated by spectroscopic analysis including NMR experiments and their absolute configurations determined based on circular dichroism data. Shoreaketone has 10 asymmetric carbons and a framework of fused heptacyclic ring system including a spiro ring and an α,β-unsaturated carbonyl group that has not been reported in any other natural product. NMR experiments using shoreaketone indicate the presence of two conformers due to restricted rotation of a C–C bond in solution. The complex stereochemistry is due to its skeleton, 10 asymmetric carbons, and a chiral axis. The conformations of rotational isomeric stilbenoid were studied by variable-temperature NMR, ROESY, a skeletal conversion. The coexistence of two conformers for shoreaketone (1) was confirmed to be 1a and 1b, in which the diaryl-dihydrobenzofuran moiety (unit 1B) is extended below or above the plane of the cyclopentane ring (unit 1A), respectively.     

Synthesis and enantiomeric recognition ability of 22-crown-6 ethers derived from rosin acid and BINOL

Four novel chiral 22-crown-6 ethers 6a-b, 7a-b bearing hydroxyl side groups derived from rosin acid and BINOL were prepared in optically pure forms, and their enantiodiscriminating abilities towards protonated primary amines and amino acid methyl ester salts were examined by UV-vis titration methods. These receptors exhibited good chiral recognition towards the isomers (up to K_D/K_L = 6.02, ΔΔG₀ = 4.45 kJ mol⁻¹) and showed different complementarity to various chiral guests.     

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.     

Solvent-induced chirality switching in the enantioseparation of regioisomeric hydroxyphenylpropionic acids via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol

The enantioseparation of three hydroxyphenylpropionic acid isomers via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol has been demonstrated. The racemates of all three acid isomers were successfully separated with high efficiency (0.56–0.84) after single crystallization. For 2-hydroxy-3-phenylpropionic acid 4, the configuration of the less-soluble salt was controlled by the crystallization solvent: the (R)-4 salt was crystallized from water, while 2-propanol afforded the (S)-4 salt. The chiral recognition mechanism of the three acids was discussed based on the crystal structures of the diastereomeric salts.