Design of a novel inherently chiral calix[4]arene for chiral molecular recognition

A newly designed inherently chiral calix[4]arene was synthesized and resolved to an optically pure form. Enantiomeric recognition ability of the chiral calix[4]arene was examined using 1H NMR experiments with mandelic acid. In addition, the chiral calix[4]arene was applied to asymmetric reactions, as an organocatalyst.     

Facile synthesis and optical resolution of inherently chiral fluorescent calix[4]crowns: enantioselective recognition towards chiral leucinol

A series of tri-O-alkylated inherently chiral fluorescent calix[4]crowns in the cone conformations and a series of tetra-O-alkylated inherently chiral fluorescent calix[4]crowns in the partial cone conformations have been synthesized. By condensing with chiral auxiliary (S)-BINOL, the resulting diastereomers could be separated via preparative TLC. We found that the size of the crown moiety effected the separation of the diastereomers. Further, removal of the BINOL unit by hydrolysis furnished pairs of enantiomers with optical purity. Moreover, we found that a tetra-O-alkylated inherently chiral fluorescent calix[4]crown-6 in the partial cone conformation 6c showed considerable enantioselective recognition capability towards chiral leucinol.     

An electrospray ionization tandem mass spectrometric study of p-tert-butylcalix[6]arene complexation with ammonium hydroxide, and ammonium and sodium ions

The formation of complexes involving p-tert-butylcalix[6]arene with neutral and charged species has been investigated by tandem mass spectrometry combined with electrospray ionization. Complexes of p-tert-butylcalix[6]arene with NH4+ ions were observed in the ratios 1:1, 2:1, and 3:1, together with the complexes of p-tert-butylcalix[6]arene with NH4OH and Na+ ions in the ratios 1:1:1, 2:1:1, and 3:1:1. A single 1:1 complex of p-tert-butylcalix[6]arene with Na+ ions was observed. In addition, a doubly charged complex of p-tert-butylcalix[6]arene with NH4OH, Na+, and NH4+ ions in the ratio 6:1:1:1 was observed. The identity of each complex was determined by mass analysis of product ions formed by the application of a declustering potential over the range 20-220 V and by observation of product ion mass spectra wherein the collision energy was varied from 5 to 50 eV. Fragmentation of the complexes is characterized by the facile loss of the ammonia molecule, sodium and ammonium ions, loss of neutral p-tert-butylcalix[6]arene, and successive neutral losses of C4H8 from the six tert-butyl groups in each p-tert-butylcalix[6]arene molecule. Copyright     

Inherently chiral biscalixarene cone–cone conformers consisting of calix[4]arene and calix[5]arene subunits

Inherently chiral biscalixarenes with hetero-cavities were synthesized by a covalent assembly of p-tert-butylcalix[5]arene with a 1,3-substituted calix[4]arene via 1,3-alkylation reaction and subsequent desymmetrization. The racemates were resolved by chiral HPLC method. ¹H NMR spectra, VT-NMR spectra, and theoretical calculations support that the calix[5]arene subunit of the inherently chiral calix[4][5]arene ester adopts a cone-in conformation, with the aromatic ring bearing the CH₂CO₂Et group tilting inward the calix[5]arene cavity. By contrast, such a cone-in structural feature of the calix[5]arene subunit disappears for the corresponding inherently chiral calix[4][5]arene carboxylic acid, due to the intramolecular hydrogen bonding between the carboxyl group and an ethereal oxygen of the glycolic chain.     

Convenient direct synthesis of bisformylated calix[4]arenes via ipso substitution

[reaction: see text] A facile synthesis of bisformylated calix[4]arenes via ipso substitution of p-tert-butylcalix[4]arenes through treatment with hexamethylenetetramine/trifluoroacetic acid is described. Under identical conditions, p-tert-butylcalix[4]arene tetramethyl ether 4 gives proximally substituted bisformylated derivative 4a in a pinched cone conformation.     

Preparation of both antipodes of enantiopure inherently chiral calix[4]crowns

Both antipodes of enantiopure inherently chiral calix[4]crown derivatives were successfully obtained through separation of their BINOL diastereomeric derivatives of corresponding racemates using preparative TLC instead of conventional HPLC methods. Such a result provides a basis for future study of chiral recognition and asymmetric catalysis with inherently chiral calixrene derivatives.     

Synthesis and X-ray crystal structures of the first antimony and bismuth calixarene complexes

The reaction of the monosodium salt of p-tert-butylcalix[4]arene (But)C4) with 2 equivalents of SbCl3 provides ButC4(SbCl)2 and the first bismuth calixarene complex was prepared by treatment of p-tert-butylcalix[8]arene (ButC8) with Bi[N(SiMe3)2]3 in toluene.     

Synthesis and alkaline earth metal cation extraction by proton di-ionizable p-tert-butylcalix[4]arene-crown-5 compounds in cone, partial-cone and 1,3-alternate conformations

Synthetic strategies for novel, proton di-ionizable p-tert-butylcalix[4]arene-crown-5 compounds in cone, partial-cone and 1,3-alternate conformations are reported. Selective linkage of the two diametrical phenolic oxygens in p-tert-butylcalix[4]arene with tetraethylene glycol ditosylate gave 1,3-bridged p-tert-butylcalix[4]arene-crown-5. The two remaining phenolic units were alkylated using NaH and KH as the bases to give the cone and partial-cone conformers, respectively. Preparation of the 1,3-alternate conformers utilized a different sequence in which O-alkylation was followed by crown ether ring formation. Structures of these new ligands were elucidated by (1)H and (13)C NMR spectroscopy. These proton-ionizable ligands were tested for their solvent extraction properties toward alkaline earth metal cations. Surprising differences in their extraction behaviors are noted compared to those reported previously for di-ionizable p-tert-butylcalix[4]arenecrown-6 analogues.     

Synthesis and structural analysis of the polymetallated alkali calixarenes [M4(p-tert-butylcalix[4]arene-4H)(thf)x]2.n THF (M=Li,K; n=6 or 1; x=4 or 5) and [Li2(p-tert-butylcalix[4]arene-2H)(H2O)(mu-H2O)(thf)].3 THF

To study the structures and reactivities of alkali metallated intermediates of calix[4]arenes, three compounds were isolated: [Li(4)(p-tert-butylcalix[4]arene-4H)(thf)(4)](2).6 THF (1), [Li(2)(p-tert-butylcalix[4]arene-2H)(H(2)O)(mu-H(2)O)(thf)].3 THF (2), and [K(4)(p-tert-butylcalix[4]arene-4H)(thf)(5)](2).THF (3). The structure of 1 is shown to be dependent on the coordinating solvent. Partial hydrolysis of 1 leads to the formation of 2. The potassium compound 3 features a different structure to that of 1, due to a higher coordination number as well as stronger cation-pi-bonding interactions.     

Synthesis and conformational property of tannin-like p-tert-butylcalix[4]arene 1,3-diesters stabilized by intramolecular hydrogen bonds.

Tannin-like p-tert-butylcalix[4]arene 1,3-digallate was synthesized, and its conformational property was investigated by dynamic (1)H NMR and X-ray crystallography. It was found that the 3-OH (or 5-OH) group of the galloyl group in p-tert-butylcalix[4]arene 1,3-digallate is placed at the position where an unusual nonbonded close contact is observed between the OH group and the aromatic ring of the galloyl group facing each other. The calixarene 1,3-diesters of various hydroxybenzoic acids were also prepared, and the conformational properties of those calixarenes were compared with that of p-tert-butylcalix[4]arene 1,3-digallate. A significant contribution of the 3- and 5-OH groups in pendant groups toward the close contact was found. It was suggested that the conformation of p-tert-butylcalix[4]arene 1,3-digallate was stabilized by intramolecular hydrogen bonds including OH.O and OH-pi interactions.     

Calixarenes and calix[4]resorcinarenes as chiral NMR solvating agents

Calixarenes (CAs) and calix[4]resorcinarenes are cavity compounds, chiral analogues of which have the potential to be used as reagents for the differentiation of enantiomers in NMR spectroscopy. The nature of the substituent groups attached to the cavity permits the preparation of organic- or water-soluble analogues. In NMR applications, chirality of the CAs or calix[4]resorcinarene is usually achieved through the attachment of enantiomerically pure substituent groups. The use of inherently chiral analogues for chiral differentiation is less common. The range of CAs and calix[4]resorcinarenes that have been used for chiral analysis in NMR spectroscopy is reviewed.     

Chemical resolution and chiral recognition of an inherently chiral biscalix[4]arene cone–partial cone conformer

An inherently chiral biscalix[4]arene carboxylic acid cone–partial cone conformer was optically resolved into individual enantiomers by chemical resolution method using (S)-BINOL as a chiral auxiliary. The partial cone calix[4]arene component plays a crucial role in optical resolution. The title compound may interact enantiodiscriminantly with chiral aminoalcohols, especially 2-phenylglycinol.     

Enantiopure inherently chiral calix[4]arene derivatives containing quinolin-2-yl-methanol moiety: Synthesis and application in the catalytic asymmetric addition of diethylzinc to benzaldehyde

A series of novel N,O-type chiral ligands derived from enantiopure inherently chiral calix[4]arenes containing quinolin-2-yl-methanol moiety in the cone or partial-cone conformation have been synthesized and characterized. Moreover, they have been applied to the catalytic asymmetric addition of diethylzinc to benzaldehyde, which represents the first example that the inherently chiral calixarene can be used as the chiral ligands for the catalytic asymmetric synthesis.     

Effective nonenzymatic kinetic resolution of racemic m-nitro-substituted inherently chiral aminocalix[4]arenes

Effective nonenzymatic kinetic resolution of racemic m-nitro-substituted inherently chiral aminocalix[4]arenes with Boc-l-proline as the acylating reagent is described, which provides an efficient and convenient method for the enantioselective synthesis of meta-substituted aminocalix[4]arenes.     

Preparation of enantiopure inherently chiral calix[5]arenes

Enantiopure inherently chiral calix[5]arenes were successfully prepared by separation of their (R)-BINOL diastereomeric derivatives of the corresponding racemates by column chromatography instead of HPLC. A new type of inherently chiral calix[5]arene was obtained.     

含噻二唑基的对叔丁基杯[4]芳烃衍生物的合成及表征

以对叔丁基杯[4]芳烃(1)为原料, 分别与1,2-二溴乙烷、1,3-二溴丙烷在碳酸钾的存在下进行选择性烷基化反应, 生成杯[4]芳烃衍生物2和3. 在氢氧化钠存在下, 化合物2和3与过量的含不同官能团的2-巯基噻二唑反应, 生成下缘含噻二唑基的杯芳烃衍生物4a～4c, 5a～5c, 其结构经¹H NMR, ¹³C NMR, IR, MS和元素分析确证.     

Acid-promoted rearrangement of carbonate functionality anchored to the lower rim of a Calix

A unique calix[4]arene lower-rim intramolecular rearrangement, resulting in molecular asymmetry arising from the upper- and lower-rim substitution pattern, produces a new class of inherently chiral calix[4]arenes in a partial cone conformation. This was aided by molecular rigidification arising from pi-pi and C-H.pi interactions between bulky lower-rim substituents, with the corresponding circular dichroism spectra exhibiting the most intense bisignate Cotton effects yet observed for calix[4]arenes not bearing a chiral center.     

Synthesis of functionalized azacalix[3]aromatics from azacalix[4]pyrimidine: unexpected macrocyclic transannular reactions

The lower-rim formylated azacalix[4]pyrimidine underwent transannular Friedel–Crafts and dehydrogenative cross coupling reactions to afford, respectively, 2,4,5,7-tetraaza-9,10-dihydroacridine and -dihydroacridin-9-one containing azacalix[3]aromatics. Dihalogenation of the later compound produced resolvable inherently chiral azacalix[3]aromatics.     

Proximal heteroalkylation of monoalkoxycalix[4]arenes in synthesis of inherently chiral molecules

Proximal heteroalkylation of monoalkyl ethers of calix[4]arenes or p-tert-butylcalix[4]arenes in NaH/CH₃CN or NaOH/DMSO, respectively, was applied for synthesis of inherently chiral calixarenes with ABHH substitution pattern. The introduction by the method of (R)- or (S)-N-(α-phenylethyl)acetamide chiral auxiliary group gives mixtures of diastereomeric derivatives of inherently chiral calixarenes, which were separated by column chromatography. The chiral calixarenes were thoroughly characterized by ¹H, ¹³C NMR, and X-ray diffraction methods.     

Synthesis and optical resolution of a series of inherently chiral calix[4]crowns with cone and partial cone conformations

A series of inherently chiral calix[4]arenes with cone and partial cone conformations and with crown ether moieties of variable size have been readily synthesized. By taking advantage of the carboxy appendage on the lower rim, these were condensed with the chiral auxiliary (S)-BINOL to form diastereomers which, in most cases, could be separated by preparative TLC, or more desirably, by column chromatography on silica gel (diastereomeric excess >99 % based on HPLC analysis). Seven enantiopure antipodes of inherently chiral calix[4]crowns were obtained after hydrolysis. It has been found that both the size of the crown moiety and alkylation of the last phenolic hydroxy group (accompanied with or without a change in the conformation) affect the separation of the diastereomers.