Racemate resolution via diastereomeric helicates in hydrogen-bonded co-crystals: the case of BINOL–diamine complexes

The structures of a series of co-crystals formed by enantiomers of BINOL (2,2′-dihydroxy-1,1′-binaphthalene) with (R,R)-1,2-diaminocyclohexane (DACH) and (R,R)-1,2-diamino-1,2-diphenylethane have been determined by X-ray diffraction to investigate the factors responsible for diastereoselective co-crystallization, the process responsible for the highly effective resolution of rac-BINOL by DACH. The absolute configurations of the molecules and directional preferences of the hydrogen bonds in the supramolecular aggregates have been analyzed. The supramolecular aggregation of hydrogen-bonded BINOL and diamines shows considerable distortions from the helical shape, which indicates that cohesion forces other than hydrogen bonds play a significant role in the diastereoselective resolution.     

Tailor-made chiral pyranopyrans based on glucose and galactose and studies on self-assembly of some crystals and low molecular weight organogel (LMOG)

InCl₃ catalyzed reactions of 2-C-acetoxymethylglycal derivatives with different phenolic compounds resulted in the formation of sugar based pyranoarenopyrans in good yields and moderate to excellent diastereoselectivity in favor of 10aR- or 12aR- or 14aR-products. One of the synthesized compounds, viz. (2R,3R,12aR)-2,3,5,12a-tetrahydro-2-methoxymethyl-3-methoxypyrano[2,3-b]naphtho[1,2-e]pyran gelated polar solvents like MeOH, EtOH and non-polar solvents like pentane, hexane, heptane, octane, pet. ether, etc. The SEM picture of the corresponding hexane xerogel exhibited a rare type of microtubular gel assembly, whereas the SEM pictures of MeOH and pet. ether xerogels showed different types of three-dimensional network. Study of the MeOH gel by Fluorescence spectroscopy, ¹H NMR and X-ray powder diffraction analysis indicated that the supramolecular assembly in the MeOH gel can be attributed to π-stacking. The crystal packing of (2R,3R,10aR)-3,10a-dihydro-2-methoxymethyl-3-methoxy-7-methyl-2H,5H-pyrano[2,3-b][1]benzopyran, a benzopyran analogue of the above organogelator was stabilized by C-H?O and C-H?π hydrogen bonds forming one-dimensional columns parallel to the [001] direction, whereas the corresponding benzopyran 3-epimer showed only C-H?O hydrogen bonds among the molecules.     

Solid-state optical properties of a chiral supramolecular fluorophore consisting of chiral (1R,2R)-1,2-diphenylethylenediamine and fluorescent carboxylic acid derivatives

By using (1R,2R)-1,2-diphenylethylenediamine as a chiral molecule and 2-anthracenecarboxylic acid as a fluorescent molecule, we created a chiral supramolecular organic fluorophore having circularly polarized luminescence properties in the solid-state.     

Reaction of arylenedioxytrihalophosphoranes with acetylenes 12. Alkylacetylenes in the reaction with 2,2,2-trihalobenzo-1,3,2-dioxaphospholes

A reaction of 2,2,2-trihalobenzo-1,3,2-dioxaphospholes with terminal alkylacetylenes proceeds under mild conditions (～20 °C) and leads to the formation of 4-alkylbenzo[e]-1,2-oxaphosphinine 2-oxide derivatives. The presence of aliphatic substituents in acetylene decreases (as compared to their aromatic counterparts described earlier) regioselectivity of halogenation of benzo fragment in 4-alkylbenzo[e]-1,2-oxaphosphinines: besides predominant 4-alkyl-2,6-dihalobenzo[e]-1,2-oxaphosphinines, minor 2,7- and 2,8-dihalo-substituted 4-alkylbenzo[e]-1,2-oxaphosphinines are formed. An unusual thermal isomerization of 4-alkyl-2-fluorobenzo[e]-1,2-oxaphosphinines to 4-alkylidene-2-fluoro-3,4-dihydrobenzo[e]-1,2-oxaphosphinines was discovered. Molecular and supramolecular structures of some 4-alkylbenzo[e]-1,2-oxaphosphinines were studied by X-ray diffraction analysis.     

Tuning mechanism in helical columnar thiophene host system with 2-thienylacetic acid by using (1R,2S)-2-amino-1,2-diphenylethanol

A tunable supramolecular thiophene host system with a chiral channel-like cavity is developed using (1R,2S)-2-amino-1,2-diphenylethanol. This thiophene host system possesses a chiral helical columnar structure. The chiral cavities are formed by the self-assembly of the helical column, and guest molecules are included by varying the helical structure and packing arrangement of this column.     

Control of release properties of guest molecules by the type of benzoheterocyclic ring in supramolecular host complexes

Three types of supramolecular benzoheterocyclic host complexes were successfully prepared using (1R,2S)-2-amino-1,2-diphenylethanol and three types of benzoheterocyclic (benzothiophene, benzofuran, and benzopyrrole) acid derivatives. The host complexes had one-dimensional (1D) channel-like cavities that were formed by the assembly of two-component 2₁-helical columnar network structures, which included guest alcohol molecules. The release behavior of the guest molecules could be tuned by the type of heterocyclic ring in the supramolecular host complex.     

Lipase-mediated kinetic resolution of cis-1,2-indandiol and the Ritter reaction of its mono-acetate

Lipase-mediated kinetic resolution of cis-1,2-indandiol 5 in the presence of lipase PS was examined. Enantiomerically enriched (1S,2R)-2-acetoxy-1-indanol 6a was obtained when cis-1,2-indandiol 5 was treated with one equivalent of vinyl acetate. Treatment of 5 with two equivalents of vinyl acetate furnished a mixture of (1R,2S)-2-acetoxy-1-indanol 6a and (1R,2S)-1-acetoxy-2-indanol 6b. A route to both enantiomers of 1 was also developed by using the enantiomerically enriched mono-acetate thus obtained.     

Formation of chiral 21-helical columnar host system with phenylacetylene unit by using (1R,2S)-2-amino-1,2-diphenylethanol

A tunable supramolecular phenylacetylene host system with a chiral channel-like cavity is developed by using (1R,2S)-2-amino-1,2-diphenylethanol. This host system possesses a chiral 2₁-helical columnar structure; chiral cavities are constructed by the self-assembly of the 2₁-helical column, and guest molecules are included by varying the packing of this column.     

Crystal structure of N,N-disalicylidene-(R,S)(S,R)-1,2-ethanediamine

N,N-disalicylidene-(R,S)(S,R)-1,2-ethanediamine crystallizes in orthorhombic space group Pbca with a = 9.5634(6), b = 14.2917(9), c = 16.9181(8) Å and Z = 4. The crystal structure was solved by direct methods and refined by full-matrix least squares to final values R1 = 0.0 + 399 and wR2 = 0.1004 with 2755 reflections (I > 2σ(I)). The N,N-disalicylidene-(R,S)(S,R)-1,2-ethanediamine molecules exhibit intramolecular N-H...O and are connected by C-H...O and C-H...π interactions to form a 2D supramolecular network.     

An efficient synthesis of chiral isoquinuclidines by Diels-Alder reaction using Lewis acid catalyst

The Diels-Alder reaction of 1,2-dihydropyridine derivatives (1-phenoxycarbonyl-1,2-dihydropyridine 1 or 1-methoxycarbonyl-1,2-dihydropyridine 4) with N-acryloyl (1S)-2,10-camphorsultam (1S)-2 {or N-acryloyl (1R)-2,10-camphorsultam (1R)-2} in the presence of Lewis acid, such as titanium tetrachloride, zirconium tetrachloride, and hafnium tetrachloride afforded the endo-cycloaddition product, 2-azabicyclo[2.2.2]octane derivatives in good yields with excellent diastereoselectivity. The absolute stereochemistry assignment of the endo-cycloaddition product (1S)-5a starting from N-acryloyl (1S)-2,10-camphorsultam (1S)-2 has been established to be (1S,4R,7S) and the reaction mechanism was proposed.     

Dendrimer-Like Chiral Stationary Phases Derived from (1R, 2R)-(+)-1,2-Diphenylethylenediamine and 1,3,5-Benzenetricarbonyl Trichloride

Three dendrimers were synthesized directly on aminated silica gel using (1R, 2R)-(+)-1,2-diphenylethylenediamine and 1,3,5-benzenetricarbonyl trichloride as building blocks. The chiral stationary phases were obtained by modification of these dendrimers with phenyl isocyanate. All derivatives prepared on silica gel were characterized by FTIR spectrum, solid-state ¹H NMR and elemental analysis. The enantioseparation ability of the chiral stationary phases was preliminarily evaluated by high-performance liquid chromatography. The chiral stationary phase of one-generation dendrimer exhibited best enantioseparation ability.     

Ti-mediated addition of diethylzinc to benzaldehyde. The effect of chiral additives

In the presence of a chiral tridentate bissulfonamide, the titanium-mediated addition of diethylzinc to benzaldehyde gave alkylated products ranging from the (R)-enantiomer, formed with an e.e. of 26%, to the (S)-enantiomer, formed in 72% e.e. The enantioselectivity was also affected by the presence of additional chiral mono- and bidentate ligands, with the reactions proceeding via complexes containing the chiral sulfonamide and the additive. The addition of (1R,2R)-1,2-diphenyl-1,2-ethanediamine and (1S,2S)-1,2-diphenyl-1,2-ethanediamine gave the (S)-product with e.e. of 49% and the (R)-product with 16% e.e., respectively, whereas without additives the (R)-product was obtained in 26% e.e. In the presence of (1R,2R)-1,2-diphenyl-1,2-ethanediamine only (i.e. without the chiral sulfonamide), the (S)-product formed with a 3% e.e.     

Stereoselective synthesis of novel benzoins catalysed by benzaldehyde lyase in a gel-stabilised two-phase system

Asymmetric benzoin condensation was performed using recombinant benzaldehyde lyase (BAL) from Pseudomonas fluorescens Biovar I. To enable the conversion of hydrophobic substrates, the enzyme was entrapped in polyvinyl alcohol and suspended in hexane. Compared to the reported application of the biocatalyst in an aqueous phase containing 20% DMSO, the productivity of the resulting gel-stabilised two-phase system was 3-fold better. The entrapment process had an efficiency of >90%, no enzyme or cofactor was lost during reaction or storage. The entrapped enzyme was stable in hexane for 1 week at 4 °C and more than 1 month at −20 °C. Without preceding optimisation the novel benzoins (R)-1,2-di(3-furanyl)-2-hydroxyethanone, (R)-2-hydroxy-1,2-di(3-thienyl) ethanone, (R)-1,2-di(4-ethoxyphenyl)-2-hydroxyethanone, (R)-1,2-di(3-ethoxyphenyl)-2-hydroxyethanone, (R)-2-hydroxy-1,2-di(3-tolyl)ethanone, and (R)-1,2-di(benzofuran-2-yl)-2-hydroxyethanone were prepared with yields up to 31.8% and enantiomeric excess >99%.     

Enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by C2-symmetric chiral diols

Optically pure C₂-symmetric diols have been synthesized with moderate yields in a straightforward manner, and are used as catalysts in the enantioselective alkylation of aromatic aldehydes with diethylzinc. The addition of diethylzinc to benzaldehyde and sterically hindered 1-naphthaldehyde was achieved with excellent enantioselectivities (97–99% ee) under catalysis with (1R,2R)-1,2-bis(3,5-dibromophenyl)-ethane-1,2-diol and (1R,2R)-1,2-bis(3,5-diphenylphenyl)-ethane-1,2-diol.     

Stereoselective carbon–carbon bond forming reactions of chiral cyclopent-2-enone and cyclopentene-1-methanol,both spiro-connecting a 1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl ring

The conjugate additions of a variety of organocopper reagents or dimethyl malonate anion to a spirocyclic cyclopent-2-enone connecting a 1,2:5,6-di-O-isopropylidene-α-d-glucofuranosyl ring as a constituent of the spiro structure, namely (1S,3R,4R,5R)-3,4-(isopropylidenedioxy)-1-[(1R)-1,2-(isopropylidenedioxy)ethyl]-2-oxa-spiro[4.4]non-6-en-8-one, proceeded stereoselectively in some cases affording a variety of β-functionalized cyclopentanone derivatives. The thermal treatment of (1S,3R,4R,5R)-7-(hydroxymethyl)-3,4-(isopropylidenedioxy)-1-[(1R)-1,2-(isopropylidenedioxy)ethyl]-2-oxaspiro[4.4]non-6-ene, another d-glucose-derived spirocyclic substrate, with triethyl orthoacetate in the presence of a catalytic amount of acid afforded the Claisen rearrangement product with a high level of diastereoselectivity.     

New pincer-like receptor derived from trans-cyclopentane-1,2-diamine as a chiral shift reagent for carboxylic acids

A new pincer-like enantiopure receptor bearing two (1R,2R)-cyclopentane-1,2-diamine moieties has been synthesized and tested as a chiral shift reagent (CSR) for different carboxylic acids. This CSR is efficient for those acids bearing an aromatic group attached to Cα, especially for arylpropionic acids. A full structural study of the diastereomeric supramolecular complexes has allowed us to propose a reasonable model for the interaction.     

Chiral relay in NHC-mediated asymmetric β-lactam synthesis II; asymmetry from NHCs derived from acyclic 1,2-diamines

The synthesis of a range of imidazolinium salts derived from acyclic 1,2-diamines, and an evaluation of the reactivity and asymmetric induction of the corresponding NHCs as catalysts for the asymmetric synthesis of β-lactams, is reported. An N-methyl-substituted NHC derived from (1R,2R)-1,2-diphenylethanediamine shows optimal reactivity and enantioselectivity in this series, in contrast to that observed with NHCs derived from (1R,2R)-cyclohexane-1,2-diamine.     

New non-C2-symmetric phosphine-phosphonites as ligands in asymmetric metal catalysis

Starting from 1,2-dibromobenzene, the synthesis of N,N,N′,N′-tetraethyl-[2-(diphenylphosphino)phenyl]phosphonous acid tetraamide is possible in two simple steps. This key compound reacts with a variety of chiral diols such as (R)- and (S)-binaphthol, 1,2:5,6-diisopropylidene-d-mannitol or (1R,2R)-1,2-diphenyl-1,2-ethane diol to form the corresponding non-C₂-symmetric phosphine-phosphonite compounds. These ligands react with Rh(COD)₂BF₄ to form bidentate Rh-complexes which serve as catalysts in the asymmetric hydrogenation of dimethyl itaconate with ee values of up to 88%.     

Solvation controlling reaction paths and gel-formation in imide derivatives

1,8-Naphthalic anhydride condenses with 4-nitro-1,2-diaminobenzene in acetic acid to give 11-nitrobenzo[d,e]benzo[2,1-a]isoquinoline-1,3-dione (1), whereas the same reaction carried out in DMF gives 2-(2-amino-4-nitrophenyl)-benzo[d,e]isoquinoline-1,3-dione (2). The condensation reaction of 1,8-naphthalic anhydride with 1-amino 3,5-benzene dicarboxylic acid leads to corresponding imide, which forms a gel in a mixed solvent such as water in DMSO. A similar compound 5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-isophthalic acid derived from phthalic anhydride forms gel in a mixed solvent of DMSO and water, whereas a crystalline solvate of DMSO with 2 could be obtained upon crystallization from DMSO. The crystal structure of this solvate is determined and its structure is compared with 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-benzoic acid. The latter does not form a gel in the mixed solvent and adopts an intermolecular hydrogen bonded structure.     

New heterogenized C2-symmetric bis(sulfonamide)-cyclohexane-1,2-diamine-RhCp∗ complexes and their application in the asymmetric transfer hydrogenation (ATH) of ketones in water

C₂-symmetric bis(sulfonamide) ligands derived from chiral trans-(1R,2R)-cyclohexane-1,2-diamine were immobilized on silica gel and on polystyrene resin, and complexed to Rh^IIICp∗. The resulting complexes were used as catalysts in the asymmetric transfer hydrogenation (ATH) of acetophenone. The chiral secondary alcohol was obtained in high yields (>99%) and enantioselectivities (92%) with aqueous sodium formate as the hydride source. The immobilized catalysts were recycled with no loss in activity.