catena‐Poly[[[μ‐1,3‐bis(diphenylphosphanyl)propane‐κ2P:P′][O‐ethyl (4‐methoxyphenyl)phosphonodithioato‐κ2S,S′]silver(I)] chloroform monosolvate]

Reaction of a mixture of AgOAc, Lawesson's reagent [2,4‐bis(4‐methoxyphenyl)‐1,3‐dithiadiphosphetane‐2,4‐disulfide] and 1,3‐bis(diphenylphosphanyl)propane (dppp) under ultrasonic treatment gave the title compound, {[Ag(C₉H₁₂O₂PS₂)(C₂₇H₂₆P₂)]·CHCl₃}_n, a novel one‐dimensional chain based on the in situ‐generated bipodal ligand [ArP(OEt)S₂]⁻ (Ar = 4‐methoxyphenyl). The compound consists of bidentate bridging 1,3‐bis(diphenylphosphanyl)propane (dppp) and in situ‐generated bidentate chelating [ArP(OEt)S₂]⁻ ligands. The dppp ligand links the [Ag{ArP(OEt)S₂}] subunit to form an achiral one‐dimensional infinite chain. These achiral chains are packed into chiral crystals by virtue of van der Waals interactions. No π–π interactions are observed in the crystal structure.     

4,4,4′,4′,7,7′‐Hexamethyl‐2,2′‐spirobichroman

The title compound, C₂₃H₂₈O₂, was obtained from the reaction of acetone with meta‐cresol. The molecular structure consists of two identical subunits which are nearly perpendicular to each other. The oxygen‐containing rings are not planar and the molecule is chiral. The crystal structure consists of chains of molecules of the same chirality arranged along the [010] axis.     

Chiral crystals from an achiral molecule: 4,6‐di‐O‐benzyl‐1,3‐O‐benzylidene‐2‐O‐(4‐methoxybenzyl)‐myo‐5‐inosose

The title achiral compound, C₃₅H₃₄O₇, crystallizes in the chiral monoclinic space group P2₁. The molecules are densely packed to form a helical assembly along the crystallographic twofold screw axis via C—H...O and C—H...π interactions. Interestingly, the unit‐translated helical chains are loosely connected via a rather uncommon edge‐to‐edge Ph—H...H—Ph short contact (H...H = 2.33 Å).     

(2,2′‐Bi­pyridine‐κ2N,N′)(dichromato‐κO)copper(II)

The title compound, [Cu(Cr₂O₇)(C₁₀H₈N₂)₂], a new mixed‐metal molecular compound, contains isolated molecular units, each comprised of one Cu^II atom coordinated to two 2,2′‐bi­pyridine ligands and also to an oxy­gen vertex of a dichromate anion. The Cu^II atom has an approximate trigonal–bipyramidal geometry, which is consistent with previous studies. Both enantiomers of the chiral complex mol­ecule are present and are related by inversion centers. In a reported pyridine analogue, achiral [Cu(Cr₂O₇)(pyridine)₄] chains pack in the non‐centrosymmetric space group Pna2₁. Differences in the organic ligands influence the chirality and dimensionality of the Cu—Cr₂O₇ bonding.     

The hydrogen‐bonding patterns of 3‐phenylpropylammonium benzoate and 3‐phenylpropylammonium 3‐iodobenzoate: generation of chiral crystals from achiral molecules

The crystal structures and hydrogen‐bonding patterns of 3‐phenylpropylammonium benzoate, C₉H₁₄N⁺·C₇H₅O₂⁻, (I), and 3‐phenylpropylammonium 3‐iodobenzoate, C₉H₁₄N⁺·C₇H₄IO₂⁻, (II), are reported and compared. The addition of the I atom on the anion in (II) produces a different hydrogen‐bonding pattern to that of (I). In addition, the supramolecular heterosynthon of (II) produces a chiral crystal packing not observed in (I). Compound (I) packs in a centrosymmetric fashion and forms achiral one‐dimensional hydrogen‐bonded columns through charge‐assisted N—H...O hydrogen bonds. Compound (II) packs in a chiral space group and forms helical one‐dimensional hydrogen‐bonded columns with 2₁ symmetry, consisting of repeating R₄³(10) hydrogen‐bonded rings that are commonly observed in ammonium carboxylate salts containing chiral molecules. This hydrogen‐bond pattern, which has been observed repeatedly in ammonium carboxylate salts, thus provides a means of producing chiral crystal structures from achiral molecules.     

Lipase‐Catalyzed Dynamic Kinetic Resolution of C1‐ and C2‐Symmetric Racemic Axially Chiral 2,2′‐Dihydroxy‐1,1′‐biaryls

We have discovered that the racemization of configurationally stable, axially chiral 2,2′‐dihydroxy‐1,1′‐biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase‐catalyzed kinetic resolution led to the first lipase/metal‐integrated dynamic kinetic resolution of racemic axially chiral biaryl compounds. The method was applied to the synthesis of various enantio‐enriched C₁‐ and C₂‐symmetric biaryl diols in yields of up to 98 % and enantiomeric excesses of up to 98 %, which paves the way for new developments in the field of asymmetric synthesis.     

N,N′‐Bis(2‐hydroxycyclohexyl)‐N,N′‐bis(2‐hydroxyethyl)ethane‐1,2‐diaminium dichloride

The achiral meso form of the title compound, C₁₈H₃₈N₂O₄²⁺·2Cl⁻, crystallizes to form undulating layers consisting of chains linked via weak hydroxyalkyl C—H...Cl contacts. The chains are characterized by centrosymmetric hydrogen‐bonded dimers generated via N—H...Cl and hydroxycycloalkyl O—H...Cl interactions. trans‐N‐Alkyl bridges subdivide the chains into hydrophilic segments flanked by hydrophobic cycloalkyl stacks along [001].     

A Cinchona Alkaloid‐Functionalized Mesostructured Silica for Construction of Enriched Chiral β‐Trifluoromethyl‐β‐Hydroxy Ketones over An Epoxidation‐Relay Reduction Process

A cinchona alkaloid‐functionalized heterogeneous catalyst is prepared through a thiol‐ene click reaction of chiral N‐(3,5‐ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co‐condensation of 1,2‐bis(triethoxysilyl)ethane and 3‐(triethoxysilyl)propane‐1‐thiol. Structural analyses and characterizations disclose its well‐defined chiral single‐site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral β‐trifluoromethyl‐β,β‐disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral β‐trifluoromethyl‐β‐hydroxy ketones through a sequential epoxidation‐relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4‐trifluoro‐1,3‐diphenylbut‐2‐enone, showing an attractive feature in a practical construction of enriched chiral β‐CF₃‐substituted molecules.     

Oxazoline chemistry part III. Synthesis and characterisation of [2‐(2′‐anilinyl)‐2‐oxazolines] and some related compounds

The syntheses and characterisation of a series of chiral and achiral 2‐(aminophenyl)‐2‐oxazolines and some related compounds is reported. All of the derivatives have been produced by a one‐step procedure involving the treatment of isatoic anhydride (i.e. [2H]‐3, 1‐benzoxazine‐[1H‐2,4‐dione: 1 ) or its 5‐chloro analogue with a slight excess of appropriate amino‐alcohols. In most cases, anhydrous ZnCl₂ is shown to be an effective Lewis acid catalyst for this reaction at reflux temperature in high boiling aromatic solvents (PhCl or PhMe). Oxazolines have been readily formed using rac‐2‐amino‐1‐butanol, (S)‐phenylglycinol, 2‐methyl‐2‐amino‐1‐propanol and (1S,2R) or (IR,2S)‐cis‐ 1 ‐amino‐2‐indanol; yields range from 85% to 22%. The use of aminoalcohols such as 2‐ethanolamine, (±)‐2‐amino‐1‐phenyl‐1‐propanol or 3‐amino‐1‐propanol (to give the corresponding 4,5‐dihydro‐1,3‐oxazine) results in poor yields. The use of other Lewis acid catalysts (silicic acid, Cd(acac)₂·2H₂O, CuCl₂·2H₂O, InCl₃) or higher temperatures did not improve the yields with these latter two substrates. Benzoxazoles and N‐substituted benzoxazoles can also be obtained in reasonable yields from 1 using 2‐aminophenol (36%) or 2‐amino‐3‐hydroxypyridine (45%).     

A Flexible Approach to Azasugars: Asymmetric Total Syntheses of (+)‐Castanospermine, (+)‐7‐Deoxy‐6‐epi‐castanospermine,and (+)‐1‐epi‐Castanospermine

The asymmetric total synthesis of natural azasugars (+)‐castanospermine, (+)‐7‐deoxy‐6‐epi‐castanospermine, and synthetic (+)‐1‐epi‐castanospermine has been accomplished in nine to ten steps from a common chiral building block (S)‐ 8 . The method features a powerful chiral relay strategy consisting of a highly diastereoselective vinylogous Mukaiyama‐type reaction with either chiral or achiral aldehydes (≥95 % de; de=diastereomeric excess) and a diastereodivergent reduction of tetramic acids, which allows formation of three continuous stereogenic centers with high diastereoselectivities. The method also provides a flexible access to structural arrays of 5‐(α‐hydroxyalkyl)tetramic acids, such as 17/34 , and 5‐(α‐hydroxyalkyl)‐4‐hydroxyl‐2‐pyrrolidinones, such as 18 and 25/35 a . The method constitutes the first realization of the challenging chiral synthons A and D and thus of the conceptually attractive retrosynthetic analysis shown in Scheme 1 in a highly enantioselective manner.     

Optimization of the HPLC enantioseparation of 3,3′‐dibromo‐5,5′‐disubstituted‐4,4′‐bipyridines using immobilized polysaccharide‐based chiral stationary phases

The HPLC enantioseparation of nine atropisomeric 3,3′,5,5′‐tetrasubstituted‐4,4′‐bipyridines was performed in normal and polar organic (PO) phase modes using two immobilized polysaccharide‐based chiral columns, namely, Chiralpak IA and Chiralpak IC. The separation of all racemic analytes, the effect of the chiral selector, and mobile phase (MP) composition on enantioseparation and the enantiomer elution order (EEO) were studied. The beneficial effect of nonstandard solvents, such as tetrahydrofuran (THF), dichloromethane (DCM), and methyl t‐butyl ether on enantioseparation was investigated. All selected 4,4′‐bipyridines were successfully enantioseparated on Chiralpak IA under normal or PO MPs with separation factors from 1.14 to 1.70 and resolutions from 1.3 to 6.5. Two bipyridines were enantioseparated at the multimilligram level on Chiralpak IA. Differently, Chiralpak IC was less versatile toward the considered class of compounds and only five bipyridines out of nine could be efficiently separated. In particular, on these columns, the ternary mixture n‐heptane/THF/DCM (90:5:5) as MP had a positive effect on enantioseparation. An interesting phenomenon of reversal of the EEO depending on the composition of the MP for the 3,3′‐dibromo‐5,5′‐bis‐(E)‐phenylethenyl‐4,4′‐bipyridine along with an exceptional enantioseparation for the 3,3′‐dibromo‐5,5′‐bis‐ferrocenylethynyl‐4,4′‐bipyridine (α = 8.33, R_s = 30.6) were observed on Chiralpak IC.     

Catalytic Enantioselective α‐Ketol Rearrangement

A highly enantioselective α‐ketol rearrangement has been developed. In the presence of a chiral Cu‐bisoxazoline complex, achiral β‐hydroxy‐α‐dicarbonyls were isomerized to chiral α‐hydroxy‐β‐dicarbonyls and their bicyclic derivatives in excellent yields and enantioselectivities. Enantioenriched 2‐acyl‐2‐hydroxy cyclohexan‐1‐ones, dihydroxyhexahydrobenzofuranones, and dihydroxyhexahydro‐cycloheptafuranones, with up to three stereocenters, were readily prepared from achiral starting materials in one operation. The reaction is applicable to the desymmetrization of meso substrates and kinetic resolution of racemic alcohols.     

2,3,3′,6‐Tetra‐O‐acetyl‐4,1′,6′‐trichloro‐4,1′,4′,6′‐tetradeoxygalactosucrose

At 160 K, one of the Cl atoms in the furanoid moiety of 3‐O‐acetyl‐1,6‐di­chloro‐1,4,6‐tri­deoxy‐β‐d ‐fructo­furan­osyl 2,3,6‐tri‐O‐acetyl‐4‐chloro‐4‐deoxy‐α‐d ‐galacto­pyran­oside, C₂₀H₂₇­Cl₃O₁₁, is disordered over two orientations, which differ by a rotation of about 107° about the parent C—C bond. The conformation of the core of the mol­ecule is very similar to that of 3‐O‐acetyl‐1,4,6‐tri­chloro‐1,4,6‐tri­deoxy‐β‐d ‐tagato­furanos­yl 2,3,6‐tri‐O‐acetyl‐4‐chloro‐4‐deoxy‐α‐d ‐galacto­pyran­oside, particularly with regard to the conformation about the glycosidic linkage.     

Crystallographic report: [N,N′‐Bis‐(6‐methylpyrid‐2‐ylium)‐(1R,2R)‐1,2‐diaminocyclohexane] bis‐[(p‐cymene)‐ trichlororuthenate(II)]

The chiral compound (H₂cydiampy)[RuCl₃(p‐cymene)]₂ has been obtained in high yield by treating [RuCl₂(p‐cymene)]₂ with an excess of hydrochloric acid in the presence of one equivalent of N,N′‐bis‐(6‐methylpyrid‐2‐yl)‐(1R,2R)‐1,2‐diaminocyclohexane (cydiampy). It crystallizes in the chiral tetragonal space group P4₃2₁2, with half of the atoms of the dication related to the other half by a crystallographic C₂ axis that also makes equivalent the two anionic metal moieties. Copyright © 2005 John Wiley & Sons, Ltd.     

NMR characterization of 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate binding to chiral molecular micelles

NMR spectroscopy was used to characterize the binding of the chiral compound 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate (BNP) to five molecular micelles with chiral dipeptide headgroups. Molecular micelles have covalent linkages between the surfactant monomers and are used as chiral mobile phase modifiers in electrokinetic chromatography. Nuclear overhauser enhancement spectroscopy (NOESY) analyses of (S)‐BNP:molecular micelle mixtures showed that in each solution the (S)‐BNP interacted predominately with the N‐terminal amino acid of the molecular micelle's dipeptide headgroup. NOESY spectra were also used to generate group binding maps for (S)‐BNP:molecular micelle mixtures. In these maps, percentages are assigned to the (S)‐BNP protons to represent the relative strengths of their interactions with a specified molecular micelle proton. All maps showed that (S)‐BNP inserted into a previously reported chiral groove formed between the molecular micelle's dipeptide headgroup and hydrocarbon chain. In the resulting intermolecular complexes, the (S)‐BNP protons nearest to the analyte phosphate group were found to point toward the N‐terminal Hα proton of the molecular micelle headgroup. Finally, pulsed field gradient NMR diffusion experiments were used to measure association constants for (R) and (S)‐BNP binding to each molecular micelle. These K values were then used to calculate the differences in the enantiomers' free energies of binding, Δ(ΔG). The NMR‐derived Δ(ΔG) values were found to scale linearly with electrokinetic chromatography (EKC) chiral selectivities from the literature. Copyright © 2010 John Wiley & Sons, Ltd.     

Kinetic Resolution of Racemic Secondary Benzylic Alcohols by the Enantioselective Esterification Using Pyridine‐3‐carboxylic Anhydride (3‐PCA) with Chiral Acyl‐Transfer Catalysts

Pyridine‐3‐carboxylic anhydride (3‐PCA) was found to function as an efficient coupling reagent for the preparation of carboxylic esters from various carboxylic acids with alcohols under mild conditions by a simple experimental procedure. This novel condensation reagent 3‐PCA was applicable not only for the synthesis of achiral carboxylic esters catalyzed by 4‐(dimethylamino)pyridine (DMAP) but also for the production of chiral carboxylic esters by the combination of chiral nucleophilic catalyst, such as tetramisole (=2,3,5,6‐tetrahydro‐6‐phenylimidazo[2,1‐b][1,3]thiazole) derivatives. An efficient kinetic resolution of racemic benzylic alcohols with achiral carboxylic acids was achieved by using 3‐PCA in the presence of (R)‐benzotetramisole ((R)‐BTM), and a variety of optically active carboxylic esters were produced with high enantiomeric excesses by this new chiral induction system without using a tertiary amine.     

One‐dimensional CuII coordination polymers containing C2h‐symmetric 1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylate linkers

Two new one‐dimensional Cu^II coordination polymers (CPs) containing the C_2h‐symmetric terphenyl‐based dicarboxylate linker 1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylate (3,3′‐TPDC), namely catena‐poly[[bis(dimethylamine‐κN)copper(II)]‐μ‐1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylato‐κ⁴O,O′:O′′:O′′′] monohydrate], {[Cu(C₂₀H₁₂O₄)(C₂H₇N)₂]·H₂O}_n, (I), and catena‐poly[[aquabis(dimethylamine‐κN)copper(II)]‐μ‐1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylato‐κ²O³:O^3′] monohydrate], {[Cu(C₂₀H₁₂O₄)(C₂H₇N)₂(H₂O)]·H₂O}_n, (II), were both obtained from two different methods of preparation: one reaction was performed in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO) as a potential pillar ligand and the other was carried out in the absence of the DABCO pillar. Both reactions afforded crystals of different colours, i.e. violet plates for (I) and blue needles for (II), both of which were analysed by X‐ray crystallography. The 3,3′‐TPDC bridging ligands coordinate the Cu^II ions in asymmetric chelating modes in (I) and in monodenate binding modes in (II), forming one‐dimensional chains in each case. Both coordination polymers contain two coordinated dimethylamine ligands in mutually trans positions, and there is an additional aqua ligand in (II). The solvent water molecules are involved in hydrogen bonds between the one‐dimensional coordination polymer chains, forming a two‐dimensional network in (I) and a three‐dimensional network in (II).     

A three‐dimensional homochiral metal–organic framework constructed from manganese(II) with S‐carboxymethyl‐N‐(p‐tosyl)‐l‐cysteine and 4,4′‐bipyridine

In the chiral polymeric title compound, poly[aqua(4,4′‐bipyridine)[μ₃‐S‐carboxylatomethyl‐N‐(p‐tosyl)‐l ‐cysteinato]manganese(II)], [Mn(C₁₂H₁₃NO₆S₂)(C₁₀H₈N₂)(H₂O)]_n, the Mn^II ion is coordinated in a distorted octahedral geometry by one water molecule, three carboxylate O atoms from three S‐carboxyatomethyl‐N‐(p‐tosyl)‐l ‐cysteinate (Ts‐cmc) ligands and two N atoms from two 4,4′‐bipyridine molecules. Each Ts‐cmc ligand behaves as a chiral μ₃‐linker connecting three Mn^II ions. The two‐dimensional frameworks thus formed are further connected by 4,4′‐bipyridine ligands into a three‐dimensional homochiral metal–organic framework. This is a rare case of a homochiral metal–organic framework with a flexible chiral ligand as linker, and this result demonstrates the important role of noncovalent interactions in stabilizing such assemblies.     

Copper‐Complex‐Catalyzed Asymmetric Aerobic Oxidative Cross‐Coupling of 2‐Naphthols: Enantioselective Synthesis of 3,3′‐Substituted C1‐Symmetric BINOLs

A novel chiral 1,5‐N,N‐bidentate ligand based on a spirocyclic pyrrolidine oxazoline backbone was designed and prepared, and it coordinates CuBr in situ to form an unprecedented catalyst that enables efficient oxidative cross‐coupling of 2‐naphthols. Air serves as an external oxidant and generates a series of C₁‐symmetric chiral BINOL derivatives with high enantioselectivity (up to 99 % ee) and good yield (up to 87 %). This approach is tolerant of a broader substrates scope, particularly substrates bearing various 3‐ and 3′‐substituents. A preliminary investigation using one of the obtained C₁‐symmetric BINOL products was used as an organocatalyst, exhibiting better enantioselectivity than the previously reported organocatalyst, for the asymmetric α‐alkylation of amino esters.     

Design of Binaphthyl‐Modified Symmetrical Chiral Phase‐Transfer Catalysts: Substituent Effect of 4,4′,6,6′‐Positions of Binaphthyl Rings in the Asymmetric Alkylation of a Glycine Derivative

A series of symmetrical chiral phase‐transfer catalysts with 4,4′,6,6′‐tetrasubstituted binaphthyl units have been designed, and these aryl‐ and trialkylsilyl‐substituted phase‐transfer catalysts, which included a highly fluorinated catalyst, were prepared. The chiral efficiency of these chiral phase‐transfer catalysts was investigated in the asymmetric alkylation of tert‐butylglycinate–benzophenone Schiff base under mild phase‐transfer conditions, and the eminent substituent effect of the 4,4′,6,6′‐positions of the binaphthyl units on enantioselection was observed. In particular, the OctMe₂Si‐substituted catalyst was found to be highly efficient for the phase‐transfer alkylation of tert‐butylglycinate–benzophenone Schiff base with various alkyl halides, including sec‐alkyl halides. The highly fluorinated catalyst was also utilized as a recyclable chiral phase‐transfer catalyst by simple extraction with fluorous solvents.