Protonation Of Enolates Research Articles

ChemInform Abstract: Investigations into the Enantioselective Protonation of Enolates Derived from 2-Methyl-1-tetralone Using a Chiral Diamine Ligand.

Abstract The synthesis of enantiomerically enriched (+)-( R )-2-methyl-1-tetralone 1 (up to 47% e.e.) was achieved by enantioselective protonation of an achiral lithium enolate 3 using a chiral diamine additive in the presence of acetic acid. We discuss the factors (like salt effects and chelation) that are responsible for this observed enantioselectivity and comment on the role of the achiral acid.

ChemInform Abstract: Preparation of a Fluorous Chiral BINOL Derivative and Application to an Asymmetric Protonation Reaction.

Fluorous Chiral Proton Source (R,S)-FDHPEB resulted in a higher enantioselectivity (95% ee) than that of the original nonfluorous (R,S)-DHPEB (87% ee) in an enantioselective protonation of a samarium enolate. (R,S)-FDHPEB was easily recovered by a simple filtration through a fluorous reverse phase silica gel and was recyclable.

ChemInform Abstract: Catalytic Enantioselective Protonation of Lithium Enolates with Chiral Imides.

The catalytic enantioselective protonation of simple enolates was achieved using a catalytic amount of chiral imides and stoichiometric amount of achiral proton sources. Among the achiral proton so...

Catalytic Asymmetric Protonation of Chiral Calcium Enolates via 1,4-Addition of Malonates

Catalytic asymmetric protonation of chiral calcium enolates was performed. Chiral calcium enolates, prepared in situ from imides and malonates via 1,4-addition in the presence of catalytic amounts of Ca(OEt)(2), Ph-PyBox, and achiral phenol, were smoothly protonated to afford adducts bearing tertiary asymmetric carbons in high yields with high enantioselectivities. The adducts were readily converted to optically active 2-substituted 1,5-dicarboxylic acid derivatives.

Benzothiazolylazo derivatives of some β-dicarbonyl compounds and their Cu(II), Ni(II) and Zn(II) complexes

The coupling of diazotized 2-aminobenzothiazole with 1,3- dicarbonyl compounds (benzoylacetone, methylacetoacetate and acetoacetanilide) yielded a new series of tridentate ligand systems (HL). Analytical, IR, 1H-NMR, 13C-NMR and mass spectral data indicated that the compounds exist in the intramolecularly hydrogen bonded azo-enol tautomeric form in which one of the carbonyl groups of the dicarbonyl moiety had enolised and hydrogen bonded to one of the azo nitrogen atoms. The compounds formed stable complexes with Ni(II), Cu(II) and Zn(II) ions. The Cu(II) complexes conform to [CuL(OAc)] stoichiometry while the Ni(II) and Zn(II) complexes are in agreement with [ML2] stoichiometry. Analytical, IR, 1H-NMR, 13C-NMR and mass spectral data of the complexes are consistent with the replacement of the chelated enol proton of the ligand with a metal ion, thus leading to a stable sixmembered chelate ring involving a cyclic nitrogen, one of the azo nitrogens and the enolate oxygen. The Zn(II) chelates are diamagnetic while Cu(II) and Ni(II) complexes showed a normal paramagnetic moment.

The Role of Charge in the Surfactant-Assisted Stabilization of the Natural Product Curcumin

Colloidal solutions of surfactants that form micelles or vesicles are useful for solubilizing and stabilizing hydrophobic molecules that are otherwise sparingly soluble in aqueous solutions. In this paper we investigate the use of micelles and vesicles prepared from ionic surfactants for solubilizing and stabilizing curcumin, a medicinal natural product that undergoes alkaline hydrolysis in water. We identify spectroscopic signatures to evaluate curcumin partitioning and deprotonation in surfactant mixtures containing micelles or vesicles. These spectroscopic signatures allow us to monitor the interaction of curcumin with charged surfactants over a wide range of pH values. Titration data are presented to show the pH dependence of curcumin interactions with negatively and positively charged micelles and vesicles. In solutions of cationic micelles or positively charged vesicles, strong interaction between the Cur(-1) phenoxide ion and the positively charged surfactants results in a change in the acidity of the phenolic hydrogen and a lowering of the apparent lowest pK(a) value for curcumin. In the microenvironments formed by anionic micelles or negatively charged bilayers, our data indicates that curcumin partitions as the Cur(0) species, which is stabilized by interactions with the respective surfactant aggregates, and this leads to an increase in the apparent pK(a) values. Our results may explain some of the discrepancies within the literature with respect to reported pK(a) values and the acidity of the enolic versus phenolic protons. Hydrolysis rates, quantum yields, and molar absorption coefficients are reported for curcumin in a variety of solutions.

Efficient Deracemization of Pipecolic Acid Amides through Enantioselective Protonation of Their Lithium Enolates: Insights into the Origin of the Transferred Proton

AbstractA detailed study of the deracemization of pipecolic acid amides is reported. Enantioselective protonation of the lithium enolates of these amides with use of commercially available ephedrines led to enantiomeric excesses (ee values) higher than 99 %. The success of the reaction was strongly dependent on the following parameters: the base, the reaction temperature, the structure of the chiral source, and the achiral quenching reagent. sBuLi and the bimetallic base “potassium alkoxide/nBuLi” were the only bases to allow complete formation of the enolate in conjunction with high stereocontrol of the protonation. Experiments with (+)‐ or(–)‐ephedrine derivatives as chiral sources and deuteriated reagents gave evidence that both the OH and NH protons of ephedrine were involved in the stereoinduction. External delivery of the proton was mainly operative with the aniline derivative (+)‐5, as shown by deuterium labeling experiments, whereas internal quenching was the major pathway observed with ephedrine (6). Finally, the deracemization procedure was successfully applied to prepare both enantiomers of N‐protected pipecolic acid from racemic pipecolic acid (51 % overall yield, 99 % ee).(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

ChemInform Abstract: Enantioselective Enolate Protonations: Friedel—Crafts Reactions with α‐Substituted Acrylates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric Kinugasa Reaction of Cyclic Nitrones and Nonracemic Acetylenes

Kinugasa reactions between chiral acetylenes and five-membered nitrones, achiral and bearing a stereogenic center in both enantiomeric forms, proceed in moderate to good yield with high diastereoselectivity affording mostly one dominant product. The first step of the reaction is controlled by the configuration of the nitrone, whereas the protonation of intermediate enolate in the second step depends mainly on the configuration of the bridgehead carbon atom formed in the first step. In the case of the mismatched pair, the configuration at the C-6 center of the carbapenam skeleton may also be affected by the configuration of the stereogenic center in the acetylene portion.

Enantioselective Enolate Protonations: Friedel–Crafts Reactions with α‐Substituted Acrylates

Enantioselective Enolate Protonations: Friedel–Crafts Reactions with α‐Substituted Acrylates

Enantioselective Enolate Protonations: Friedel–Crafts Reactions with α‐Substituted Acrylates

Enantioselective Enolate Protonations: Friedel–Crafts Reactions with α‐Substituted Acrylates

Catalytic Enantioselective Tautomerization of Isolated Enols

Smells like roses: The catalytic enantioselective ketonization of two isolated enols was successful and made possible the discussion of the important mechanistic implications of these findings. The indirect enolate protonation occurs via enols and higher-order mixed aggregates (see scheme). The reaction was used to synthesize the rose-smelling fragrance compound (S)-α-damascone.

Chiral Pyridine-Catalyzed HN3-Addition to Ketenes

Catalytic enantioselective addition of hydrazoic acid to unsymmetric ketenes 1 followed by thermally induced Curtius rearrangement of initially formed acid azides 4 gives rise to optically enriched protected amines of the general form 3. Moderate steric congestion and electron-rich aromatic groups on the ketene proved beneficial. Unhindered phenyl ethyl ketene furnished almost racemic product. Catalyst (+)-2, a planar-chiral pyridine derivative, structurally related to the well-established DMAP motifs (see review below), was found to effectively mediate the addition step. According to their mechanistic proposal, protonated (+)-2 acts as a chiral Brønsted acid achieving the enantioselective protonation of achiral enolate 5.

Hyperconjugative effect of C–Ge bonds: synthesis of multisubstituted alkenylgermanes via torquoselective olefination of acylgermanes with ynolates

The first highly Z-selective olefination of acylgermanes with ynolates affording multisubstituted alkenylgermanes was achieved. The torquoselectivity was ascribed to the hyperconjugative effect of C–Ge bonds in the transition state. The resulting ( Z)-β-trialkylgermylacrylic acid has a hypervalent structure, which was converted into novel germalactones. A stereochemical complementary olefination via protonation of the β-lactone enolate, followed by decarboxylation, was also achieved.

Stereoelectronic Effects Dictate Mechanistic Dichotomy between Cu(II)-Catalyzed and Enzyme-Catalyzed Reactions of Malonic Acid Half Thioesters

Previously we developed a Cu(II)-catalyzed, enantioselective aldol reaction between malonic acid half thioesters (MAHTs) and aldehydes based on the biosynthesis of polyketides and fatty acids in which MAHTs are decarboxylated enzymatically to afford ester enolates that condense with thioesters. We report evidence based on steric effects, kinetics, kinetic isotope effects, and crossover experiments in support of a different mechanism for the Cu(II)-catalyzed aldol reaction involving enolization of MAHTs by deprotonation, addition to the aldehyde, decarboxylation, and protonation of the β-hydroxy enolate. We also provide an explanation, based on stereoelectronic effects, for the mechanistic dichotomy between Cu(II)-catalyzed and enzyme-catalyzed reactions of MAHTs.

Stereochemical investigation on the construction of poly-functionalized bicyclo[3.3.1]nonenones by successive Michael reactions of 2-cyclohexenones

A method for the practical construction of poly-functionalized bicyclo[3.3.1]nonenones by successive Michael reactions of cyclohexenones with acrylates using K2CO3 and TBAB (n-Bu4N+ Br-) was developed. The construction could be carried out in both stepwise and one-pot reactions with similar tendencies in regioselectivity. The alpha-regioselectivity in the intramolecular Michael reaction agreed with that stereoelectronically expected in intermolecular reactions based upon consideration of the HOMO orbital profile of the enolate I, the precursor to ring-closure, although the reaction site was trisubstituted and prone to steric hindrance in most of the examples presented. For the acetoxymethylacrylates substituted at either the alpha or gamma position, steric hindrance of the substituents (R2 and R3) served as a controlling factor to induce high regiocontrol. Facial selection in the protonation of enolate II, formed upon ring-closure, was also affected by these substituents. In both the intramolecular Michael reaction and the protonation of enolate II, the ammonium counter cation played an important role.

Synthesis and Reactivity of New Mono‐ and Dinuclear Hydridoirida‐β‐diketones – The Formation and Characterization of a Dinuclear Tris‐μ‐acyliridium(III) Complex

AbstractThe hydridoirida‐β‐diketone [IrH{[PPh2(o‐C6H4CO)]2H}Cl] (1) reacts with silver salts of potentially coordinating anions such as tosylate (–OTs) or triflate (–OTf) to afford the mononuclear neutral derivatives [IrH{[PPh2(o‐C6H4CO)]2H}(X)] [X = OTs (2), OTf (3)]. In acetone solution the triflate anion in 3 is displaced by the solvent to afford the cationic complex [IrH{[PPh2(o‐C6H4CO)]2H}(acetone)]OTf (4), which is stable only in acetone solution. The reaction of 1 with halide scavengers containing less coordinating anions such as PF6– or BF4– results in the formation of cationic compounds [{IrH[{PPh2(o‐C6H4CO)}2H]}2(μ‐Cl)]A [A = BF4 (5), PF6 (6)] containing a dinuclear species with a single chlorine atom bridging two hydridoirida‐β‐diketone fragments. Both fragments are magnetically non‐equivalent and the acylphosphane groups in each hydridoirida‐β‐diketone fragment are chemically equivalent. This species undergoes a fluxional process in solution, with ΔH‡ = 7.8 ± 0.4 kcal mol–1 and ΔS‡ = –10.9 ± 0.5 eu. A combination of rotation around the Ir–Cl bonds and variation of the Ir–Cl–Ir angle is suggested to be responsible for the fluxionality. Complex 5 reacts further with AgBF4 to undergo chloride abstraction along with hydrogen loss and deprotonation to give the cationic dinuclear complex [Ir2H{PPh2(o‐C6H4CO)}{μ‐PPh2(o‐C6H4CO)}3]BF4 (7), which contains an acylphosphane chelate along with three acylphosphane bridging ligands and a single hydrido ligand. Bubbling of HCl through an MeOH solution of 7 gives 1, thus making the loss of hydride, enolic protons and chloride from complex 1 a reversible process. All the complexes were fully characterized spectroscopically. Single‐crystal X‐ray diffraction analysis was performed on complexes 5 and 7. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Theoretical study on physicochemical properties of curcumin

Curcumin is a yellow-orange pigment, which has attracted considerable attention due to its wide spectrum of biological and pharmacological activities. In spite of much effort devoted on curcumin, there still exist some open questions concerning its fundamental physicochemical properties. The present study suggests that the DFT and TD-DFT calculations are useful to answer these questions. Firstly, the thermodynamic as well as spectral parameters support that curcumin exists predominantly in enol form in solution. Secondly, the calculated absorption spectra of curcumin anions provides direct evidence that the lowest p K a of curcumin corresponds to the dissociation of enolic proton, which not only reconciles the controversy on this topic, but also has important implications on the proton-transfer/dissociation-associated radical-scavenging mechanisms of curcumin.

Organocatalyzed route to enantioenriched pipecolic esters: decarboxylation of an aminomalonate hemiester

Enantioenriched pipecolic esters were prepared in good yields in the decarboxylation, at room temperature, of N-protected piperidinohemimalonates catalyzed by cinchona alkaloids. Enantiomeric excesses as high as 72% were obtained when using 9-epi-cinchonine and the N-benzoyl substituted piperidinohemimalonate. A detailed study of the different reaction parameters revealed that the selectivity of this noncovalent organocatalyzed reaction is strongly dependent on the solvent, toluene or carbon tetrachloride being the best ones. The whole process based on the malonic acid synthesis was successfully tested on a 10 mmolar scale and established a practical alternative to the asymmetric protonation of lithium enolates.

Catalytic Asymmetric Protonation of Lithium Enolates Using Amino Acid Derivatives as Chiral Proton Sources

[reaction: see text] Asymmetric protonation of lithium enolates was examined using commercially available amino acid derivatives as chiral proton sources. Among the amino acid derivatives tested, Nbeta-l-aspartyl-l-phenylalanine methyl ester was found to cause significant asymmetric induction in the protonation of lithium enolates. The enantiomeric excess (up to 88% ee) of the products obtained in the presence of a catalytic amount of the chiral proton source was higher than those obtained in the stoichiometric reaction.