Protonation Of Enolates Research Articles

Conformational effects in the diastereoselective protonation of chiral enolates derived from 2,4-dimethyl-1-tetralone using carbonyl chelating proton donors

The synthesis of syn-2,4-dimethyl-1-tetralone 6 via a reprotonation strategy using chelating proton donors is discussed. We comment on the comformational effects associated with these acids, and discuss the differences between direct protonation and deprotonation-reprotonation of chiral enolates in the presence of diisopropylamine and LiBr.Key words: conformation, chelating proton donors, deprotonation-reprotonation strategy, diastereoselective protonation and solvent effects.

Diastereoselective protonation of lactam enolates derived from (R)-phenylglycinol. A novel asymmetric route to 4-phenyl-1,2,3, 4-tetrahydroisoquinolines.

Highly diastereoselective protonation of chiral lactam enolates of 4-substituted-1,4-dihydroisoquinolin-3-ones is reported. Protonation and alkylation processes of these lactam enolates derived from phenylglycinol occur with opposite diastereofacial selectivity. This diastereoselective protonation has been applied to the asymmetric synthesis of (4S)-N-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 9 obtained in up to 97% ee.

The structure of benzoyldimedone from X-ray diffraction analysis

The structure of benzoyldimedone was established by X-ray diffraction analysis. The only tautomer was found. In this tautomer, the enol proton is covalently bound to the oxygen atom that is remote from the phenyl group. The role of steric and electronic factors in stabilization of the enol structure is analyzed. The geometric characteristics of the ring formed through an intramolecular hydrogen bond are discussed.

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 sources examined in the protonation of the lithium enolate of 2,2,6-trimethylcyclohexanone catalyzed by (S,S)-imide 1, 2, 6-di-tert-butyl-p-cresol (BHT) and its derivatives gave the highest enantiomeric excess. For example, 90% ee of (R)-enriched ketone was obtained when (S,S)-imide 1 (0.1 equiv) and BHT (1 equiv) were used. Use of 0.01 equiv of the chiral catalyst still caused a high level of asymmetric induction. For catalytic protonation of the lithium enolate of 2-methylcyclohexanone, chiral imide 6 possessing a chiral amide portion was superior to (S,S)-imide 1 as a chiral proton source and the enolate was effectively protonated with up to 82% ee.

Enantioselective Enolate Protonation with Chiral Anilines: Scope, Structural Requirements, and Mechanistic Implications

High enantioselectivity has been demonstrated in the protonation of N,N-diisopropyl amides (Table 1, entries 1−4, 7, and 10−13) derived from certain β,γ unsaturated acids. Depending on double bond ...

Diastereoselective synthesis of non-proteinogenic alpha-amino acids.

The synthesis of enantiomerically pure azatyrosine, tribromophenylalanine and trichlorophenylalanine is described, using two methods, diastereoselective alkylation and (or) diastereoselective protonation of chiral enolates.

ChemInform Abstract: Enantioselective Enolate Protonation: Matching Chiral Aniline and Substrate Acidity.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

Investigations into the enantioselective protonation of enolates derived from 2-methyl-1-tetralone using a chiral diamine ligand

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.

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.

Conformational effects in the diastereoselective protonation of chiral enolates derived from 2,4-dimethyl-1-tetralone using carbonyl chelating proton donors

Conformational effects in the diastereoselective protonation of chiral enolates derived from 2,4-dimethyl-1-tetralone using carbonyl chelating proton donors

Catalytic asymmetric protonation of achiral lithium enolates mediated by a chiral tetraamine ligand with water as a proton source

Catalytic protonation of achiral lithium enolates (derived from 2-substituted-1-tetralones), mediated by a chiral tetraamine ligand [( R, R)- N, N′-bis[1-phenyl-2-(1-piperidinyl)ethyl]-1,3-propanediamine (0.10 equiv.)], was achieved with high enantioselectivity (up to 93% ee) by using water (10% aqueous citric acid) as a proton source. A possible mechanism of highly efficient catalytic turnover of the chiral tetraamine ligand is discussed.

ChemInform Abstract: Asymmetric Protonation of Lithium Enolate Using 5‐Substituted Pyrrolidin‐2‐one as a Chiral Proton Source.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

Stereoselective Reactions of N-(9-Phenylfluoren-9-yl)-4-oxoproline Enolates. An Expedient Route for the Preparation of Conformationally Restricted Amino Acid Analogues

Methodology for the stereoselective preparation of 3-alkylprolines from N-(9-phenylfluoren-9-yl)-4-oxoproline is presented. The enolate of a N-(9-phenylfluoren-9-yl)-4-oxoproline ester was shown to give stereoselective aldol condensations with aromatic and aliphatic aldehydes. The enolate was preferentially approached by the electrophile through the Re face, and high threo selectivity was also observed and provided a route to trans 3-substituted prolines. The reactions are kinetically controlled except for the case of electron-rich or sterically hindered aromatic aldehydes. The ease of the equilibration between the erythro- and threo-aldolates is dictated by the electronic nature of the group at C-4 in substituted benzaldehydes, and the steric compression of the aldehyde group increases the rate of erythro/threo equilibration. Very high stereoselection was also observed in the reductions of the keto group in 3-substituted 4-oxoproline esters. Alkylation or Michael additions of the same enolate were poorly stereoselective, probably due to equilibration of the initially formed products. Kinetic protonation of enolates of 3-alkyl-4-oxoprolines proceeded with high diastereoselection to provide the corresponding cis-3-alkylprolines.

Novel Catalytic Hydrogenolysis of Trimethylsilyl Enol Ethers by the Use of an Acidic Ruthenium Dihydrogen Complex.

The heterolytic cleavage of H(2) is the key to the novel catalytic hydrogenolysis of trimethylsilyl enol ethers catalyzed by [RuCl(eta(2)-H(2))(dppe)(2)]OTf (dppe = 1,2-bis(diphenylphosphanyl)ethane, OTf = trifluoromethanesulfonate), which results in the formation of a ketone and Me(3)SiH (see scheme). In addition, the stoichiometric, ruthenium-assisted protonation of a prochiral lithium enolate with H(2) gave a chiral ketone with high enantioselectivity (up to 75 % ee).

Enantioselective Protonation of Lithium Enolates with Chiral Imides Possessing a Chiral Amide

Abstract New chiral imides possessing a chiral amide can be prepared from 1,3,5-trimethyl-r-1,c-3,c-5-cyclohexanetricarboxylic acid or related triacids and optically active amines. These imides are superior to 1,3,5-trimethyl-c-5-[(4S,5S)-4,5-diphenyl-2-oxazolin-2-yl]-r-1,c-3-cyclohexanedicarboximide reported previously as a chiral proton source for enantioselective protonation of lithium enolates of 2-alkylcycloalkanones.

Enantioselective Enolate Protonation: Matching Chiral Aniline and Substrate Acidity

A comparison of chiral anilines 1a−f in the asymmetric protonation of enolate 15 shows that the optimum ΔpKa value (chiral acid vs protonated enolate) for the highest enantioselectivity is ca. 3 (Table 2). An extension of this concept to amino acid enolates was possible, and 1e was found to give the best enantioselectivity (85% ee) with the alanine-derived N-lithioenolate 5a (Table 3). Changes in aniline pKa due to variation of substituents at the aniline nitrogen were evaluated briefly, but these changes did not show consistent trends in the enantioselectivity vs pKa.

Diastereoselective protonation of chiral enolates derived from 2,4-dimethyl-1-tetralone using carbonyl chelating proton donors

The synthesis of syn-2,4-dimethyl-1-tetralone 6 via a deprotonation-reprotonation strategy using chelating proton sources is discussed. We comment on the differences between direct protonation and deprotonation-reprotonation of chiral enolates in the presence of diisopropylamine and LiBr.

Role of lysine 240 in the mechanism of yeast pyruvate kinase catalysis.

Site-directed mutagenesis was used to change Lys 240 of yeast pyruvate kinase (Lys 269 in muscle PK) to Met. K240M has an absolute requirement for FBP for catalysis. K240M is 100- and 1000-fold less active than wild-type YPK in the presence of Mn(2+) and Mg(2+), respectively. Steady-state fluorescence titration data suggest that the substrate PEP binds to K240M with the same affinity as it does to wild-type YPK. The rate of phosphoryl transfer in K240M has been decreased >1000-fold compared to wild-type YPK. The detritiation of 3-[(3)H]pyruvate catalyzed by YPK occurs at a rate significantly greater than the spontaneous rate. Detritiation of pyruvate by wild-type YPK occurs as a divalent metal- and FBP-dependent process requiring ATP. There is no detectable detritiation of pyruvate catalyzed by K240M. The solvent deuterium isotope effect on k(cat) is 2.7 +/- 0.2 and 1.6 +/- 0.1 for the wild type and for K240M YPK, respectively. This suggests that the isotope sensitive step in the PK reaction does not involve Lys 240 and that the enolpyruvate intermediate is still protonated by K240M. Isotope trapping was used to characterize enolpyruvate protonation by K240M. While there was enrichment of the methyl protons of pyruvate from labeled solvent formed by catalysis with muscle PK and wild-type YPK, only background levels of tritium were trapped with K240M. In K240M, the proton donor exchanges protons with the solvent at a higher rate relative to turnover than does the proton donor in wild-type YPK. The pH-rate profile of K240M exhibits the loss of a pK(a) value of 8. 8 observed with wild-type YPK. The above data and recent crystal structure data suggest that Lys 240 interacts with the phosphoryl group of phosphoenolpyruvate and helps to stabilize the pentavalent phosphate transition state during phosphoryl transfer. Phosphoryl transfer is highly coupled to proton transfer, or Lys 240 also affects enolate protonation.

Enantioselective protonation of samarium enolates derived from α-heterosubstituted ketones and lactone by SmI 2-mediated reduction

SmI 2-mediated reductive cleavage of α-hetero substituents of α-alkyl or α-aryl ketones and lactone gave the corresponding “thermodynamic samarium enolates”. Enantioselective protonation of the samarium enolates with C 2-symmetric chiral diols afforded the corresponding ketones and lactone in moderate to high enantioselectivities.

ChemInform Abstract: Auxiliary‐Controlled Stereoselective Enolate Protonation: Enantioselective Synthesis of cis and trans Annulated Decahydroquinoline Alkaloids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.