Diastereomeric Forms Research Articles

Unsymmetric (μ-oxido)/(μ-pyrazolato) and Symmetric (μ-pyrazolato)2 Bridged Diosmium Frameworks: Electronic Structure and Magnetic Properties.

The present article deals with the structurally characterized unsymmetric oxido/pyrazolato-bridged [(bpy)2Os(III)(μ-oxido)(μ-pz)Os(III)(bpy)2](ClO4)3 ([1](ClO4)3) and symmetric dipyrazolato-bridged [(bpy)2Os(II)(μ-pz)2Os(II)(bpy)2](ClO4)2 ([2](ClO4)2) (pz = pyrazolato, bpy = 2,2'-bipyridine) complexes with the Os···Os separations of 3.484 and 4.172 Å, respectively. The anti-ferromagnetically coupled Os(III) centers [E(S = 1)-E(BS(1,1) S = 0) = 322.504 cm(-1)] in 1(3+) and diamagnetic (S = 0) 2(2+) exhibit well-resolved (1)H NMR resonances. [1](ClO4)3 shows temperature- and magnetic field-dependent paramagnetism at low magnetic field and diamagnetism at high magnetic field. 1(3+) and 2(2+) display successive metal-based oxidation processes involving the intermediate mixed-valent states and isovalent congeners: Os(IV)Os(IV) (1(5+))→Os(III)Os(IV) (1(4+))⇌Os(III)Os(III) (1(3+))⇌Os(III)Os(II) (1(2+)) and Os(III)Os(III) (2(4+))→Os(II)Os(III) (2(3+))⇌Os(II)Os(II) (2(2+)) as well as bpy-centered reductions. The effect of π donor O(2-) and σ/π-donating pz(-) in 1(3+) and 2(2+), respectively, leads to varying oxidation state of the metal ions in the isolated complexes: Os(III)Os(III) versus Os(II)Os(II). UV-visible-near-IR-electron paramagnetic resonance spectro-electrochemistry and density functional theory (DFT)/time-dependent DFT calculations collectively reveal overlapping of the metal- and ligand (pz, O, bpy)-based frontier orbitals in the delocalized mixed-valent states in 1(4+) and 1(2+) with comproportionation constant (Kc) value > 1 × 10(14) as well as in isovalent 1(3+), resulting in mixed metal/ligand to metal/ligand near-IR transitions in all the three states. The mixed-valent Os(II)Os(III) state in 2(3+) exhibits high Kc value of 1 × 10(22) corresponding to a strong electrochemical coupling situation. However, closeness of the bandwidth (Δν1/2, 4861 cm(-1)) of broad and weak intervalence charge transfer transition of 2(3+) at 1360 nm (ε/M(-1) cm(-1): 490) with the calculated Δν1/2 of 4121 cm(-1) based on the Hush formula as well as spin-density distributions of Os1: 0.811/0.799, Os2: 0.045/0042, and pz: 0.162/0.173 in meso and rac diastereomeric forms, respectively, attribute its localized class II state.

Analytical and preparative enantioseparation and main chiroptical properties of Iridium(III) bis(4,6-difluorophenylpyridinato)picolinato

Almost all Iridium(III) complexes employed both as dopants in PhOLEDs and as pharmaceuticals and fluorescence bioprobes are racemic mixtures. In this study the single enantiomers of the most stable diastereomeric form fac-trans-N–N, bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) were separated and analysed. The data obtained showed that the complex can be separated into stable optically active Λ and Δ isomers employing cellulose based chiral stationary phase both in normal and polar phase mode. Their chirality was confirmed and their absolute configuration assigned employing several methods (DFT and TDDFT calculations, CD and VCD). The CPL spectroscopy of the isolated enantiomers of FIrpic was also recorded due to its possible value in the OLEDs field. The chromatographic method was applied for a semipreparative purpose demonstrating that polar organic solvent chromatography (POSC) could be used to avoid the low-solubility issues associated with these Iridium(III) complexes. Finally, the chemical and stereochemical stability of the single isomers was evaluated under thermal stress by liquid chromatography coupled to high-resolution mass spectrometry (LC-QTOF) on both chiral and achiral columns. No racemization and/or isomerization was observed; however, the dissociation of the ancillary ligand was demonstrated employing LC-QTOF.

Mechanochemical Influence on the Stereoselectivity of Halide Metathesis: Synthesis of Group 15 Tris(allyl) Complexes

The stereochemical outcomes of reactions conducted in solution and those under mechanochemical conditions need not be the same; this is a well-established observation in organic synthesis, but few examples are known in organometallic systems. Halide metathesis is now shown to be a type of mechanochemical reaction that can produce different ratios of stereoisomers depending on whether the reagents are dissolved or ball-milled. Trihalides of As (X = I), Sb (X = Cl), and Bi (X = Cl) react with K[A′] (A′ = 1,3-(SiMe3)2C3H3) (As, Sb) or [AlA′3] (Bi) to generate the tris(allyl) complexes [EA′3]. All three complexes are found in two diastereomeric forms of C1 (R,S,S) and C3 (R,R,R) symmetry, and mechanochemical synthesis increases the C1:C3 ratio relative to that produced in hexanes solution (up to 3.3× in the case of [AsA′3]). The stereoselectivity of the metathesis in the solid state can be correlated with the asymmetric environment found in the group 15 trihalides; mechanochemical induction provides a new too...

Mass-Selective Chiral Analysis.

Three ways of realizing mass-selective chiral analysis are reviewed. The first is based on the formation of diastereomers that are of homo- and hetero- type with respect to the enantiomers of involved chiral molecules. This way is quite well-established with numerous applications. The other two ways are more recent developments, both based on circular dichroism (CD). In one, conventional or nonlinear electronic CD is linked to mass spectrometry (MS) by resonance-enhanced multiphoton ionization. The other is based on CD in the angular distribution of photoelectrons, which is measured in combination with MS via photoion photoelectron coincidence. Among the many important applications of mass-selective chiral analysis, this review focuses on its use as an analytical tool for the development of heterogeneous enantioselective chemical catalysis. There exist other approaches to combine chiral analysis and mass-selective detection, such as chiral chromatography MS, which are not discussed here.

Investigation of DOTA-Metal Chelation Effects on the Chemical Shift of (129) Xe.

Recent work has shown that xenon chemical shifts in cryptophane-cage sensors are affected when tethered chelators bind to metals. Here, we explore the xenon shifts in response to a wide range of metal ions binding to diastereomeric forms of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) linked to cryptophane-A. The shifts induced by the binding of Ca(2+) , Cu(2+) , Ce(3+) , Zn(2+) , Cd(2+) , Ni(2+) , Co(2+) , Cr(2+) , Fe(3+) , and Hg(2+) are distinct. In addition, the different responses of the diastereomers for the same metal ion indicate that shifts are affected by partial folding with a correlation between the expected coordination number of the metal in the DOTA complex and the chemical shift of (129) Xe. These sensors may be used to detect and quantify many important metal ions, and a better understanding of the basis for the induced shifts could enhance future designs.

An ameliorative protocol for the quantification of purine 5',8-cyclo-2'-deoxynucleosides in oxidized DNA.

5′,8-Cyclo-2′-deoxyadenosine (cdA) and 5′,8-cyclo-2′-deoxyguanosine (cdG) are lesions resulting from hydroxyl radical (HO·) attack on the 5′H of the nucleoside sugar moiety and exist in both 5′R and 5′S diastereomeric forms. Increased levels of cdA and cdG are linked to Nucleotide Excision Repair (NER) mechanism deficiency and mutagenesis. Discrepancies in the damage measurements reported over recent years indicated the weakness of the actual protocols, in particular for ensuring the quantitative release of these lesions from the DNA sample and the appropriate method for their analysis. Herein we report the detailed revision leading to a cost-effective and efficient protocol for the DNA damage measurement, consisting of the nuclease benzonase and nuclease P1 enzymatic combination for DNA digestion followed by liquid chromatography isotope dilution tandem mass spectrometry analysis.

2+2] Photocycloaddition of Cinnamates in Flow and Development of a Thiourea Catalyst.

Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers.

2+2] Photocycloaddition of Cinnamates in Flow and Development of a Thiourea Catalyst

AbstractCyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers.

Synthesis of three strong UV-absorbing Naproxen-based chiral derivatizing agents and their application for enantioseparation of Baclofen by RP-HPLC

A sensitive and stereoselective high-performance liquid chromatography (HPLC) method based on diastereomer formation was developed and fully validated for the simultaneous determination of the two enantiomers of Baclofen. (S)-Naproxen was used to prepare three chiral derivatizing reagents (CDRs) which were used for synthesizing diastereomers of Baclofen. The diastereomers so synthesized were separated on C18 column under reversed phase conditions using a binary mixture of acetonitrile and triethylammonium phosphate, with UV detection at 220 nm. The results obtained for enantioseparation of Baclofen using the three CDRs have been compiled and compared. The conditions for derivatization and chromatographic separation have been optimized. The method was validated for linearity, repeatability, limits of detection, and limit of quantification.

Palladium-Catalyzed Alkoxycarbonylation of Conjugated Enyne Oxiranes: A Diastereoselective Method for the Synthesis of 7-Hydroxy-2,3,5-trienoates.

Palladium-catalyzed alkoxycarbonylative 1,5-substitution of conjugated enyne oxiranes provides a diastereoselective route to (E)-configured 7-hydroxy-2,3,5-trienoates. The reactions proceeded in a highly stereoselective manner, possibly through sequential formation of π-allylpalladium and σ-vinylallenyl palladium complexes. The major diastereomeric form of the product is determined by the configuration of the alkenyl moiety of the substrate.

The effect of the eutectic composition on the outcome of kinetically and thermodynamically controlled resolutions that are based on the formation of diastereomers

The resolution of mandelic acid and its derivatives with free amino acids has been investigated. It was observed that the corresponding diastereomers were formed under either kinetic or thermodynamic control, which considerably influenced the purity of the enantiomeric mixtures obtained. It was found that in these particular resolutions, the eutectic composition of either the racemic compound or the resolving agent influenced the purity of the enantiomeric mixtures of the mandelic acid derivatives obtained after resolution.

Chiral sensing by nonchiral tetrapyrroles.

Enantiomeric excess (ee) is a measure of the purity of an enantiomer of a chiral compound with respect to the presence of the complementary enantiomer. It is an important aspect of chemistry, especially in the fields of pharmaceuticals and asymmetric catalysis. Existing methods for determination of enantiomeric excesses using nuclear magnetic resonance (NMR) spectroscopy mostly rely on special chiral reagents (auxiliaries) that form two or more diastereomeric complexes with a chiral compound. As a result of this, the NMR spectrum of each enantiomer is different, allowing the determination of enantiomeric excess. In this Account, we describe a molecular design process that has allowed us to prepare prochiral solvating agents for NMR determination of ee of a wide variety of analyte types. At the outset of this work, we initially encountered the phenomenon of NMR peak splitting in the oxoporphyrinogen (OxP) host component of a supramolecular host-guest complex, where the extent of the splitting is apparently proportional to the guests' ee. Upon closer examination of the mechanism of action, it was found that several complicating factors, including prototropic tautomerism, macrocyclic inversion (ring-flipping), and 1:2 host-guest stoichiometry, obstruct potential applications of OxP as a chiral solvating agent. By considering the molecular conformation of the OxP host, a saddle-shaped calix[4]pyrrole, we moved to study the tetraphenylporphyrin (TPP) dication since it has a similar form, and it was found that it could also be used to probe ee. However, although TPP does not suffer from disadvantageous tautomeric processes, it is still subject to macrocyclic inversion and has the additional serious disadvantage of operating for ee sensing only at depressed temperatures. The intrinsic disadvantages of the OxP and TPP systems were finally overcome by covalently modifying the OxP chromophore by regioselective N-alkylation at one face of the molecule. This procedure yields a host Bz2OxP that undergoes 1:1 host-guest interactions, cannot be protonated (and so does not suffer drawbacks due to tautomeric processes), and can interact solely through hydrogen bonding with a much wider range of analyte types, including acids, esters, amines (including amino acid derivatives), and ketones, for the determination of their ee at room temperature. Chiral sensing, in this case, can be understood by considering the breakdown of the host's symmetry when it interacts with a chiral guest under fast exchange. Furthermore, chirality discrimination (i.e., which is the major enantiomer in a sample) can be performed by addition of a small amount of one of the known enantiomers. Adaptation of a symmetrical molecule for ee sensing presents certain intrinsic advantages, including identical binding constants of each enantiomer. Our results indicate that other symmetrical molecules might also be useful as NMR probes of enantiopurity. These systems could provide insights into important chirality principles such as majority rule, intermolecular chirality transfer, and asymmetric reactions. The Bz2OxP system is also of note from the point of view that it does not rely on the formation of diastereomers.

Determination of Carvedilol Enantiomers in Pharmaceutical Dosages by SBSE-HPLC Based on Diastereomer Formation.

A sensitive, selective and simple method for the simultaneous determination of carvedilol enantiomers in aqueous solution has been developed using stir bar sorptive extraction (SBSE) followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. This method is based on the reaction of carvedilol enantiomers with (-)-menthyl chloroformate (MCF) after extraction by the SBSE method to produce diastereomeric derivatives. The separation was achieved by use of a C18 analytical column and the influence of mobile phase composition on the enantioseparation of carvedilol was studied. The applicability of two sorptive phases, poly(methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane, were tested for extraction of carvedilol enantiomers from aqueous samples. The obtained results showed excellent linear dynamic ranges and precisions for each of them. The least limit of detection for (S)- and (R)-carvedilol obtained 8 and 11 µg L(-1), respectively, using the PA-EG sorptive phase. Inter- and intra-mean recoveries were also satisfactory, ranging from 98 to 103%, with coefficient of variation in the range of 1-5% at three fortified levels using a PA-EG coated stir bar. The proposed SBSE (PA-EG)-MCF derivatization-HPLC-UV method was successfully applied to enantioselective analysis of carvedilol in water and pharmaceutical dosages, confirming the application of this method.

A novel approach for enantioseparation as applied to (RS)‐etodolac from pharmaceutical formulations: LC MS and density functional theory support for confirmation of diastereomers so separated

In the present studies formation of diastereomers of (RS)-etodolac was confirmed using LC-MS when [M + H](+) or [M](+) were recorded for the diastereomers. The lowest energy optimized structures of two diastereomers were drawn, which confirmed the three-dimensional geometry of the diastereomers. This supports the optimized analytical separation conditions. In addition, separation of diastereomers was successful using a C18 column and a binary mixture of methanol and triethyl ammonium phosphate buffer of pH 4.5 (80:20, v/v) as mobile phase at a flow rate of 1 mL min(-1) and UV detection at 223 nm. The separation method was validated as per International Conference on Harmonization guidelines. (RS)-Etodolac was isolated from commercial tablets and purified and characterized to be used as racemic standard. Three pairs of diastereomers were synthesized using enantiomerically pure amines, namely, (R)-(+)-α-methyl benzyl amine, (S)-(-)-α,4-dimethylbenzylamine and (R)-(-)-1-cyclohexylethylamine. Derivatization reactions were carried out under conditions of stirring at room temperature (30 °C for 2 h) as well as under microwave irradiation (MWI), and the two types of diastereomers were compared. Reaction conditions for derivatization were optimized with respect to mole ratio of chiral derivatizing agent and (RS)-etodolac and MWI time. No racemization was observed throughout the study.

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes.

The cobalt(I)-catalysed 1,4-hydrovinylation reaction of allyloxytrimethylsilane and allyl alcohol with substituted 1,3-dienes leads to hydroxy-functionalised 1,4-dienes in excellent regio- and diastereoselective fashion. Those 1,4-dienols can be converted into tetrahydrofuran and pyran derivatives under indirect electrochemical conditions generating selenium or iodonium cations. The reactions proceed in good yields and regioselectivities for the formation of single diastereomers.

Recognition of fractional non-innocent feature of osmium coordinated 2,2'-biimidazole or 2,2'-bis(4,5-dimethylimidazole) and their interactions with anions.

Mononuclear complexes [Os(II)(bpy)2(H2L1)](ClO4)2 ([](ClO4)2) and [Os(II)(bpy)2(H2L2)](ClO4)2 ([](ClO4)2) incorporating two free NH protons at the back face of the coordinated H2L, and deprotonated L(2-) bridged symmetric dinuclear complexes [(bpy)2Os(II)(μ-L1(2-))Os(II)(bpy)2)](ClO4)2 ([](ClO4)2) and [(bpy)2Os(II)(μ-L2(2-))Os(II)(bpy)2)](ClO4)2 ([](ClO4)2) (bpy = 2,2'-bipyridine, H2L1 = 2,2'-biimidazole and H2L2 = 2,2'-bis(4,5-dimethylimidazole)) have been characterised. Crystal structures of [](ClO4)2 and the meso (ΔΛ) diastereomeric form of [](ClO4)2 have been determined. The crystal structure of [](ClO4)2 also reveals the hydrogen bonding interactions between its free acidic NH protons and the oxygen atoms of the perchlorate anion in the nearby asymmetric unit. Experimental and DFT/TD-DFT calculations have divulged the non-innocent feature of the doubly deprotonated L(2-) in (3+) and (3+), leading to the resonating formulation of {Os(II)(μ-L(2-))Os(III)} ↔ {Os(II)(μ-L˙(-))Os(II)}, instead of a simple mixed valent situation {Os(II)(μ-L(2-))Os(III)}. The dinuclear complexes (3+) and (3+) display one broad and moderately intense near-IR transition near 1000 nm corresponding to a mixed Os(dπ)/L(π) → Os(dπ)/L(π*) MLLMCT (metal/ligand to ligand/metal charge transfer) transition. Different experimental studies have also established the interaction of (2+) and (2+) with the selective anions.

Structural insight into the unique binding properties of pyridylethanol(phenylethyl)amine inhibitor in human CYP51.

Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The discovery of new efficient fungal CYP51 inhibitors requires an understanding of the structural requirements for selectivity for the fungal over the human ortholog. In this study, a binding mode of the pyridylethanol(phenylethyl)amine type CYP51 inhibitor to the human ortholog was determined at the atomic level. We isolated and purified a full-length human CYP51. The inhibitor-specific binding and its conformational and dynamic properties were evaluated using UV-visible and NMR spectroscopy. Considering the experimental data in docking calculations and molecular dynamics simulations, the location of the inhibitor moieties and their interactions with the enzyme active site were determined. The inhibitor binds to the enzyme in two diastereomeric forms, which have a common location of aromatic ring moieties, while the less bulky propyl chain can adapt to various hydrophobic regions of the enzyme active site. The halogenated phenyl ring binds in the substrate access channel making numerous contacts with the hydrophobic side chains, and its interactions with the unconserved residues are especially informative. The results reveal the unique binding properties of the investigated inhibitor in comparison to the azoles and provide novel directions for the design of selective fungal inhibitors.

Development and validation of an LC-MS/MS method after chiral derivatization for the simultaneous stereoselective determination of methylenedioxy-methamphetamine (MDMA) and its phase I and II metabolites in human blood plasma.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a racemic drug of abuse and its two enantiomers are known to differ in their dose-response curves. The S-enantiomer was shown to be eliminated at a higher rate than the R-enantiomer. The most likely explanation for this is a stereoselective metabolism also claimed in in vitro studies. Urinary excretion studies showed that the main metabolites in humans are 4-hydroxy 3-methoxymethamphetamine (HMMA) 4-sulfate, HMMA 4-glucuronide and 3,4-dihydroxymethamphetamine (DHMA) 3-sulfate. For stereoselective pharmacokinetic analysis of phase I and phase II metabolites in human blood plasma useful analytical methods are needed. Therefore the aim of the presented study was the development and validation of a stereoselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of MDMA, 3,4-methylenedioxyamphetamine, DHMA, DHMA 3-sulfate, HMMA, HMMA 4-glucuronide, HMMA 4-sulfate, and 4-hydroxy 3-methoxyamphetamine in blood plasma for evaluation of the stereoselective pharmacokinetics in humans. Blood plasma samples were prepared by simple protein precipitation and afterwards all analytes were derivatized using N-(2,4-dinitro-5-fluorophenyl) L-valinamide resulting in the formation of diastereomers which were easily separable on standard reverse phase stationary phases. This simple and fast method was validated according to international guidelines including specificity, recovery, matrix effects, accuracy and precision, stabilities, and limits of quantification. The method proved to be selective, sensitive, accurate and precise for all tested analytes except for DHMA.

Diverse reactivity of the cyclo-diphosphinophosphonium cation [(PtBu)₃Me]⁺: parallels with epoxides and new catena-phosphorus frameworks.

The cyclo-diphosphinophosphonium salt [(PtBu)3Me][OTf] (2) has been shown to be highly reactive toward Lewis bases, exhibiting diverse reactivity with phosphines, 4-(dimethylamino)pyridine (dmap) and chlorophosphines, providing approaches to new open-chain and cyclic catena-phosphorus frameworks. Reaction of 2 with R3P (R = Me or nPr) or dmap led to the ring-opened adducts [R3P-PtBu-PtBu-P(Me)tBu][OTf] (R = Me (4a), nPr (4b)) and [(dmap)-PtBu-PtBu-P(Me)tBu][OTf] (6), respectively. The complicated (31)P{(1)H} NMR spectra of the three compounds were simulated, evidencing the presence of two diastereomeric forms of 4a, and single diastereomers of 4b and 6. This ring-opening reactivity of the cation in 2 parallels the reactivity of isolobal epoxides with nucleophiles under acidic conditions. Compound 2 was also shown to react with a 2:1 mixture of Me2PCl and TMSOTf to form the unexpected cyclo-diphosphino-1,2-diphosphonium salt [(Me2P)2(PtBu)2][OTf]2 (8), which is postulated to result from two consecutive ring-opening and ring-closing steps. In contrast, reaction with MePCl2 furnished [(MeP)(PtBu)2(P(Me)tBu)][OTf] (9), consistent with insertion of a "MeP" moiety into the cationic phosphorus framework of 2. The importance of ring strain on the reactivity of the cation in 2 was illustrated by comparative studies of the corresponding cyclo-tetraphosphorus cation in [(PtBu)4Me][OTf] (10), which exhibits no reactivity under analogous conditions.

ChemInform Abstract: Regioselective Internal Carbonylation of the 2‐Aza‐21‐carbaporphyrin: Access to Configurationally Stable Chiral Porphyrinoids.

Reaction of paraformaldehyde with meso-tetraaryl-2-aza-21-carbaporphyrins (NCP) in the presence of a basic catalyst afforded fused lactam derivatives comprising a >C═O bridge linking the internal carbon C21 with one of the internal nitrogens. The isomer 2 with C21-C(O)-N24 bridge is formed with about 9-fold molar excess over that with C21-C(O)-N22 bridge (3). The (1)H NMR and UV-vis spectral characteristics indicate aromatic character of the derivatives. For meso-tetrakis(3',5'-dimethoxy)- and meso-tetrakis(3',4',5'-trimethoxy)-21,24-carbonyl-NCP an efficient external ring fusion by linking C3, i.e., the external carbon of the confused pyrrole, with an ortho carbon of the adjacent aryl was observed under acidic conditions, yielding derivatives 4c and 4d, comprising a linear system of five fused rings. The chirality and configurational stability of these carbonylated systems were established by a chiral stationary phase HPLC and circular dichroism. The interaction of 2 with chiral acids and alcohols leading to the formation of diastereomers was observed by (1)H NMR. Slow racemization of 2 under acidic conditions was established by HPLC and (1)H NMR and a mechanism for this process was proposed.