Chiral Carboxylate Research Articles

Cuboidal Mo3S4 and Mo3NiS4 Complexes Bearing Dithiophosphates and Chiral Carboxylate Ligands: Synthesis, Crystal Structure and Fluxionality

AbstractNew triangular Mo and W cluster complexes incorporating (S)‐lactic acid (HLac), [Mo3S4(μ‐Lac)(dtp)3(py)] (1) and [W3S4(μ‐Lac)(dtp)3(py)] (2), were prepared [dtp = (EtO)2PS2]. Analogous synthetic procedures were adapted for the synthesis of cuboidal Mo3NiS4 to yield [Mo3(Nipy)S4(py)(μ‐OAc)(dtp)3(py)] (3). The crystal structures of 1 and 3 were determined. A detailed variable‐temperature 31P{1H} and 1H NMR study of compounds 1 and 3 indicated fluxional behaviour in non‐coordinating solvents (CDCl3, CD2Cl2 and CDCl2CDCl2). A number of dynamic processes were identified involving the Mo–py site that include configuration inversion [(P) to (M)], hindered Mo–N rotation and pyridine exchange. Experiments with deuterated pyridine revealed a faster substitutional lability of Mo–py compared with Ni–py.

Colorimetric detection of achiral anions and chiral carboxylates by a chiral thiourea—phthalimide dyad

The chiral chemosensor 1, based on a thiourea-activated phthalimide, is available by four reaction steps from 4-nitrophthalimide. 1 detects fluoride, chloride, acetate, and dihydrogen phosphate anions by changes in UV-vis absorption. Fluoride in excess induces deprotonation whereas the other anions show only complex formation in the ground state. (1)H-NMR studies confirm the formation of these H-bonded complexes and the fluoride-induced receptor deprotonation in the recognition process. Moderate chiral recognition was observed for sodium D/L-lactate with K(ass)(D)/K(ass)(L) = 1.93.

Heteroditopic Chiral Uranyl–Salen Receptor for Molecular Recognition of Amino Acid Ammonium Salts

AbstractA new heteroditopic chiral uranyl–salen complex incorporating two pyrenyl groups was designed and synthesized for the recognition of ammonium salts, tetrabutylammonium (TBA) and tetramethylammonium (TMA) amino acids. UV/Vis measurements indicate the formation of 1:1 host–guest complexes with high association constants and an excellent enantiomeric discrimination between the two enantiomers of phenylalanine–TMA. T‐ROESY NMR experiments confirm cation–π and CH–π interactions between the TBA and TMA cations and the two pyrenyl arms, leading to the strong stability of the complexes. This is the first report of a uranyl receptor able to recognize chiral carboxylate guests.

Highly selective ratiometric estimation of fluoride ion based on a BINOL imidazolium cyclophane with dual-channel

A novel imidazolium cyclophane S- 1, which displays a high selectivity for the recognition toward fluoride ion, has been constructed by using BINOL as scaffold. The fluoride ion induced remarkable red shift both in absorption and emission spectra, which might allow S- 1 to be employed as a ratiometric receptor with dual-channel. The chiral recognitions of S- 1 with chiral carboxylates were also examined.

Enantioselective fluorescent sensors for chiral carboxylates based on BINOL — Synthesis and chiral recognition

The four novel derivatives of 1,1′-bi-2-naphthol (BINOL) have been prepared, and the structures of these compounds have been characterized by IR, MS, 1H and 13C NMR spectroscopy, and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and 1H NMR spectroscopy. The receptors exhibited different chiral-recognition abilities towards some enantiomers of chiral materials and formed 1:1 complexes between host and guest. The receptors exhibit excellent enantioselective fluorescent-recognition ability towards the amino acid derivatives.

DFT computational studies of hydrogen bonding-based diastereomeric complexes – Limitations and applications to enantiodifferentiation

Molecular modeling calculations using DFT at the B3LYP/6-31G(d,p) level of theory have been performed on diastereomeric complexes formed between chiral carboxylate anions and chiral urea receptors, a combination previously demonstrated to enable enantiodifferentiation by electrochemical sensing. The calculations correctly predicted the stability order of the enantiomers in acetonitrile solution when the distinction between the enantiomers was above the declared threshold reliability value of 1 kcal mol −1 for computations at this level of theory. Thus, the calculations can not only be applied to predict the likely success of undertakings using the analytical method, it can also, provided Δ E is sufficient, potentially be used to determine the absolute configuration of chiral analytes with at least the racemate in hand. The previously successful enantiodifferentiations of various amino acids and alcohols using chiral ion mobility spectroscopy (CIMS) with ( S)-2-butanol as the chiral selector were also evaluated by DFT calculations. The calculations again correctly predicted the stability order of the enantiomers when the calculated Δ E was above the threshold value though cases not providing a value for Δ E above the threshold value was problematic for this system. Attempts to address this shortcoming included an expanded conformational evaluation, a broader analytical approach, and an extended basis set.

Chiral Tetraaminophosphonium Carboxylate-Catalyzed Direct Mannich-Type Reaction

The cooperative asymmetric catalysis of chiral tetraaminophosphonium carboxylate (P,S)-1.OCOR has been established, and its synthetic utility has been successfully demonstrated by application to the highly enantioselective direct Mannich-type reaction of azlactones with N-sulfonyl imines. The present study stimulates the cultivation of the potential of the chiral quaternary onium salt catalysis by the structural modification of organic anion.

Racemic Atropisomeric N,N-Chelate Ligands for Recognizing Chiral Carboxylates via Zn(II) Coordination: Structure, Fluorescence, and Circular Dichroism

Two racemic atropisomeric N,N'-chelate ligands, bis{3,3'-[N-Ph-2-(2'-py)indolyl]} (1) and bis{3,3'-N-4-[N-2-(2'-py)indolyl]phenyl-2-(2'-py)indolyl} (2), have been found to be able to distinguish the enantiomers of Zn((R)-BrMeBu)2 and Zn((S)-BrMeBu)2 where BrMeBu = O2CCH(Br)CHMe2, with a distinct and intense CD spectral response at approximately the 10 microM concentration range. Computational studies established that the (R)-1-Zn((R)-BrMeBu)2 or (S)-1-Zn((S)-BrMeBu)2 diastereomer is more stable than (R)-1-Zn((S)-BrMeBu)2 or (S)-1-Zn((R)-BrMeBu)2. In addition, computational studies showed that the CD spectra of (S)-1-Zn((S)-BrMeBu)2 and (S)-1-Zn((R)-BrMeBu)2 are similar. (1)H NMR spectra confirmed that these two diastereomers exist in solution in about a 2:1 ratio for both complexes of 1 and 2. The distinct CD response of the racemic ligands 1 and 2 toward the chiral zinc(II) carboxylate is therefore attributed to the preferential formation of one diastereomer. The binding modes of the zinc(II) salt with ligands 1 and 2 were established by the crystal structures of the model compounds 1-Zn(tfa)2 and 2-Zn(tfa)2 (tfa = CF3CO2(-)), where the Zn(II) ion is chelated by the two central pyridyl groups in the ligand. Fluorescent titration experiments with various zinc(II) salts showed that the fluorescent spectrum of the atropisomeric ligand displays an anion-dependent change. The zinc(II) binding strength to the N,N'-chelate site of the atropisomeric ligand has been found to play a key role in the selective recognition of different chiral zinc(II) carboxylate derivatives by the racemic atropisomeric ligands.

α-Aminoxy Acids: New Possibilities from Foldamers to Anion Receptors and Channels

Naturally occurring peptides serve important functions as enzyme inhibitors, hormones, neurotransmitters, and immunomodulators in many physiological processes including metabolism, digestion, pain sensitivity, and the immune response. However, due to their conformational flexibility and poor bioavailability, such peptides are not generally viewed as useful therapeutic agents in clinical applications. In an effort to solve these problems, chemists have developed peptidomimetic foldamers, unnatural oligomeric molecules that fold into rigid and well-defined secondary structures mimicking the structures and biological functions of these natural peptides. We have designed peptidomimetic foldamers that give predictable, backbone-controlled secondary structures irrespective of the nature of the side chains. This Account presents our efforts to develop a novel class of peptidomimetic foldamers comprising alpha-aminoxy acids and explore their applications in the simulation of ion recognition and transport processes in living systems. Peptides constructed from alpha-aminoxy acids fold according to the following rules: (1) A strong intramolecular eight-membered-ring hydrogen bond forms between adjacent alpha-aminoxy acid residues (the alpha N-O turn). The chirality of the alpha-carbon, not the nature of the side chains, determines the conformation of this chiral N-O turn. (2) While homochiral oligomers of alpha-aminoxy acids form an extended helical structure (1.8 8 helix), heterochiral ones adopt a bent reverse turn structure. (3) In peptides of alternating alpha-amino acids and alpha-aminoxy acids, the seven-membered-ring intramolecular hydrogen bond, that is, the gamma-turn, is initiated by a succeeding alpha N-O turn. Thus, this type of peptide adopts a novel 7/8 helical structure. In investigating the potential applications of alpha-aminoxy acids, we have found that the amide NH units of alpha-aminoxy acids are more acidic than are regular amide NH groups, which makes them better hydrogen bond donors when interacting with anions. This property makes alpha-aminoxy acids ideal building blocks for the construction of anion receptors. Indeed, we have constructed both cyclic and acyclic anion receptors that have strong affinities and good (enantio-)selectivities toward chloride (Cl(-)) and chiral carboxylate ions. Taking advantage of these systems' preference for Cl(-) ions, we have also employed alpha-aminoxy acid units to construct a synthetic Cl(-) channel that can mediate the passage of Cl(-) ions across cell membranes. Continued studies of these peptidomimetic systems built from alpha-aminoxy acids should lead to a broad range of applications in chemistry, biology, medicine, and materials science.

Chiral anion recognition by color change utilizing thiourea, azophenol, and glucopyranosyl groups

A new colorimetric anion sensor 1 was synthesized for the chiral recognition, which accommodates a combination of three different functional groups such as chromophore (azophenol dye), binding site (thiourea group), and chiral barrier (glucopyranosyl group). The colorimetric changes of host 1 with various α-amino carboxylates as well as chiral carboxylates such as naproxen were examined.

An Exploration of Ferrocenyl Ureas as Enantioselective Electrochemical Sensors for Chiral Carboxylate Anions

The syntheses of a series of chiral ureas containing the redox-active ferrocene group are described. Each of these bind chiral carboxylates in organic solvents through hydrogen-bonding interactions, as evidenced by spectroscopic and cyclic voltammetry measurements, the latter allowing these guests to be electrochemically sensed in solution. The enantioselectivity in the complexation of the protected amino acid N-benzenesulfonylproline by a ferrocenylbenzyl host is high enough to allow opposite enantiomers to be distinguished by electrochemical means.

Structural and melting point characterisation of six chiral ammonium naphthalene carboxylate salts

The hydrogen bonded networks of ammonium carboxylate salts formed between naphthalene-2-carboxylate or naphthalene-2,6-dicarboxylate with both optically active and racemic forms of 1-phenylethylammonium are reported. In their solid state form, the ammonium carboxylate salts feature three charge-separated N–H⋯O hydrogen bonds to form two types of 1-D hydrogen bonded columns between naphthalene-2-carboxylate: (naphthalene-2-carboxylate)·((R)-1-phenylethylammonium) (1) and ((naphthalene-2-carboxylate)·((S)-1-phenylethylammonium) (2) form non-centrosymmetric hydrogen bonded columns having a two-fold screw axis, while ((naphthalene-2-carboxylate)·((RS)-1-phenylethylammonium) (3) forms centrosymmetric hydrogen bonded columns having an inversion centre. The melting points of these three salts depend on the type of hydrogen bonded network that is formed. By linking the hydrogen bonded columns through the naphthalene-2,6-dicarboxylate anion, (naphthalene-2,6-dicarboxylate)·((R)-1-phenylethylammonium)2 (4), naphthalene-2,6-dicarboxylate)·((S)-1-phenylethylammonium)2 (5) and ((naphthalene-2,6-dicarboxylate)·((RS)-1-phenylethylammonium)2 (6) form closely related 2-D hydrogen bonded sheets that decompose rather than melt.

A Novel Synthesis of Chiral Guanidinium Receptors and Their Use in Unfolding the Energetics of Enantiorecognition of Chiral Carboxylates

A novel synthetic route to the versatile chiral bicyclic guanidinium building block is described making use of l-methionine as a starting material from the natural chiral pool. Furthermore, the synthetic elaboration of this building block is shown in the construction of macrocyclic and open chain hosts, respectively. The host design employs urea functions as the connecting units and supplementary anchor groups for the complexation of anions. The binding studies of these hosts with various chiral and achiral oxoanions are performed by isothermal titration calorimetry. A trend analysis of the binding energetics in an ensemble of structurally similar guests discloses the importance of geometrical confinement of the guest. Association entropy rather than free energy (affinity) is identified as an indicator of structural uniqueness needed to distinguish configurational isomers in the recognition of enantiomeric carboxylates by the chiral guanidinium hosts.

Liquid Chromatographic Resolution of N-(3,5-Dinitrobenzoyl)-α-amino Acids on a New Chiral Stationary Phase: the First Liquid Chromatographic Utilization of a Double-Ureide Pocket for the Recognition of Chiral Carboxylate Anions

An HPLC chiral stationary phase (CSP) which has only two ureide functional groups was prepared starting from (1S,2S)-1,2-diaminocyclohexane. The CSP was successful in the resolution of various N-(3,5- dinitrobenzoyl)-α-amino acids, the separation (α) and the resolution factors (RS) being within the range of 1.11-1.35 and 2.19-5.17, respectively with the use of 20% 2-propanol in hexane containing 0.1% trifluoroacetic acid as a mobile phase. However, ethyl esters of N-(3,5-dinitrobenzoyl)-α-amino acids were not resolved or resolved with only marginal separation and resolution factors on the CSP under the identical mobile phase condition. From these results, the complexation of the carboxylate anions of analytes inside the double-ureide pocket of the CSP was expected to play some important role for the chiral recognition. In contrast, N-(3,5- dinitrobenzoyl)-α-amino acid N-propylamides were resolved on the CSP with reasonable separation and resolution factors. Enantioselective hydrogen bonding interactions between analytes and the CSP were presumed to be responsible for these resolutions.

Enantioselective Fluorescent Sensors for Chiral Carboxylates Based on Calix[4]arenes Bearing an L‐Tryptophan Unit

AbstractTwo‐armed chiral calix[4]arenes (3a–c) functionalized at the lower ring with L‐tryptophan units have been prepared and the structures of these receptors characterized by IR, MS, 1H, and 13C NMR spectroscopy and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and 1H NMR spectroscopy. The receptors exhibited different chiral recognition abilities towards some enantiomers of chiral materials and formed 1:1 complexes between host and guest. Receptor 3a exhibits excellent enantioselective fluorescent recognition ability towards the N‐Boc‐protected alanine anion and 3b reveals good enantioselective recognition ability towards the enantiomers of mandelate.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Lanthanitin: A Chiral Nanoball Encapsulating 18 Lanthanum Ions by Ferritin‐Like Assembly

A chiral supramolecule, obtained by self-assembly of 24 chiral ditopic carboxylate ligands, 18 La ions, and two carbonate anions, has been dubbed lanthanitin because of its structural resemblance to ferritin. The picture shows the molecular structure of one enantiomer of lanthanitin. Color code: La blue, carbonate C green, C gray, O red; H omitted.

Facile synthesis of ionic liquids possessing chiral carboxylates

The synthesis of 23 new chiral ionic liquids is achieved in high yield and purity by the reaction of an amino acid or a chiral carboxylic acid with tetrabutylammonium hydroxide in water.

Judging on Host−Guest Binding Mode Uniqueness: Association Entropy as an Indicator in Enantioselection

[reaction: see text] Supramolecular enantiodifferentiation was studied by isothermal titration calorimetry in an effort to address the order-disorder distinction in the diastereomeric complexes formed from a chiral macrocyclic host and enantiomeric carboxylates. As a result, the association entropy component TDeltaS emerged as an indicator in the enantioselection of tartrate 14 and aspartate 15 by the macrocycle 13 containing two guanidinium anchor groups connected to each other by four urea units. The parent monotopic guanidinium compounds 1 or 2 did not show any enantioselection for chiral carboxylates.

ChiralN-salicylidene vanadyl carboxylate-catalyzed enantioselective aerobic oxidation of α-hydroxy esters and amides

A series of chiral vanadyl carboxylates derived from N-salicylidene-L-alpha-amino acids and vanadyl sulfate has been developed. These configurationally well defined complexes were examined for the kinetic resolution of double- and mono-activated 2 degrees alcohols. The best chiral templates involve the combination of L-tert-leucine and 3,5-di-t-butyl-, 3,5-diphenyl-, or 3,4-dibromo-salicylaldehyde. The resulting vanadyl(V)-methoxide complexes after recrystallization from air-saturated methanol serve as highly enantioselective catalysts for asymmetric aerobic oxidation of alpha-hydroxyl-esters and amides with a diverse array of alpha-, O-, and N-substituents at ambient temperature in toluene. The asymmetric inductions of the oxidation process are in the range of 10 to >100 in terms of selectivity factors (k(rel)) in most instances. The previously undescribed aerobic oxidation protocol is also applicable to the kinetic resolution of C-13 taxol side chain with high selectivity factor (k(rel) = 35). X-ray crystallographic analysis of an adduct between a given vanadyl complex and N-benzyl-mandelamide allows for probing the stereochemical origin of the nearly exclusive asymmetric control in the oxidation process.

Rhodium(II)‐Catalyzed Inter‐ and Intramolecular Enantioselective Cyclopropanations with Alkyl‐Diazo(triorganylsilyl)acetates

AbstractThe intermolecular cyclopropanation of styrene with ethyl diazo(triethylsilyl)acetate (1a) proceeds at room temperature in the presence of chiral RhII carboxylate catalysts derived from imide‐protected amino acids and affords mixtures of trans‐ and cis‐cyclopropane derivatives 2a in up to 72% yield but with modest enantioselectivities (<54%) (Scheme 1 and Table 1). Protiodesilylation of a diastereoisomer mixture 2a with Bu4NF is accompanied by epimerization at C(1) (→3). The intramolecular cyclopropanation of allyl diazo(triethylsilyl)acetate (8a), in turn, affords optically active 3‐oxabicyclo[3.1.0]hexan‐2‐one (9a) with yields of up to 85% and 56% ee (Scheme 3 and Table 2). Similarly, the (2Z)‐pent‐2‐enyl derivative 8d reacts to 9d in up to 77% yield and 38% ee (Scheme 3 and Table 3). In contrast, the diazo decomposition of (2E)‐3‐phenylprop‐2‐enyl and 2‐methylprop‐2‐en‐1‐yl diazo(triethyl‐silyl)acetates (8b and 8c, resp.) is unsatisfactory and gives very poor yields of substituted 3‐oxabicyclo[3.1.0]hexan‐2‐ones 9b and 9c, respectively (Table 3).