Chiral Proton Source Research Articles

ChemInform Abstract: Preparation of Optically Active Ketones via Enantioface- Differentiating Protonation of Prochiral Enolates.

Abstract Enantioselective protonation of the prochiral lithium enolate (2) of 2-benzylcyclohexanone (3) was developed. Reaction of 2 with methyl (S)-α-hydroxyisocaproate (15) as a chiral proton source afforded (R)-3 in a high optical yield. This reaction is widely applicable to the preparation of various α-substituted optically active ketones.

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.

Straightforward Organocatalytic Enantioselective Protonation of Silyl Enolates by Means of Cinchona Alkaloids and Carboxylic Acids

The combination of cinchona alkaloids and carboxylic acids provides a very simple chiral proton source. By using this system, enantioselective protonation of silyl enolates was achieved affording the corresponding ketones in high yields and in up to 75% ee.

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

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, please click on HTML or PDF.

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.

From Overstoichiometric to Substoichiometric Enantioselective Protonation with 2‐Sulfinyl Alcohols: A View in Perspective

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Protonation of a Lithium Enolate Derived from 2‐Methyl‐1‐tetralone Using Chiral Sulfonamides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Protonation of a Lithium Enolate Derived from 2-Methyl-1-tetralone Using Chiral Sulfonamides

Abstract The synthesis of enantiomerically enriched (R)-2-methyl-1-tetralone (1) with 77% e.e. was achieved through protonation of its lithium enolate (3) using a C2-symmetric tris-sulfonamide (6) as an internal chiral proton source. Access to the complementary (S)-enantiomer 1 with 33% e.e. was achieved using a related C2-symmetric bis-sulfonamide (9) as the chiral proton source.

From overstoichiometric to substoichiometric enantioselective protonation with 2-sulfinyl alcohols: A view in perspective

A general study of the enantioselective protonation of prochiral enolates with 2-sulfinyl alcohols is reported. The modification of reaction conditions to reduce drastically the amount of chiral proton source needed to obtain a good enantiomeric excess is reported. The effects of the different factors controlling the stereoselectivity are clearly established. Different protocols for enolate generation are compared.

Enantioselective Protonation of the Lithium Transient Enolate of2‐Methyltetralone with 2‐Sulfinyl Alcohols

AbstractA new catalytic cycle for the enantioselective protonation of cyclic ketone enolates with sulfinyl alcohols has been developed. An enol trifluoroacetate that can be easily obtained from the corresponding ketone is used for the first time as an enolate precursor of a cyclic ketone enolate. In this method, the achiral alcohol plays two roles: it is involved, as is usual in catalytic asymmetric protonation reactions, in the turnover of the chiral proton source and also in the generation of a transient enolate through the reaction of its corresponding alkoxide with the enol trifluoroacetate precursor. Stereoselectivity is highly dependent on the structure of the achiral alcohol. High levels of stereoselectivity can be achieved with the use of cyclohexanol. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Enantioselective Partial Reduction of 2,5-Disubstituted Pyrroles via a Chiral Protonation Approach

[reaction: see text] The partial reduction of 2,5-pyrrole diester 1 followed by enantioselective protonation in situ to furnish synthetically useful building blocks is described. An enantiomeric excess of up to 74% was achieved using (-)-ephedrine and related analogues as chiral proton sources. The pyrroline product obtained could be recrystallized to give enantiomerically pure material.

Synthesis of an enantiopure 2-arylcyclohexanols from prochiral enol acetates by an enantioselective protonation/diastereoselective reduction sequence

The enantioselective protonation with 2-sulfinyl alcohols of lithium enolates of 2-arylcyclohexanones with different substituents on the phenyl group takes place with excellent enantioselectivities (89–99%). Chiral 2-phenylcyclohexanone and 2-arylcyclohexanones carrying electron donor substituents on the aromatic ring are converted into the corresponding trans-2-arylcyclohexanols by diastereoselective reduction with sodium naphthalenide in the presence of acetamide. The stereochemical integrity of the tertiary stereocenter is fully preserved using this reduction procedure. Interestingly, the chiral proton source is not consumed in the synthesis.

Enantioselective protonation of prochiral enolates in the asymmetric synthesis of ( S)-naproxen

Racemic methyl, iso-propyl, and tert-butyl ester derivatives of naproxen were treated with achiral LDA base to give the corresponding prochiral enolates 2 -Li, 3 -Li, and 4 -Li. Protonation of these enolates with novel chiral proton sources ( S)- 10 and ( S, S)- 11 , containing the α-phenylethylamino group, proceeded in a highly enantioselective manner. Saponification of enantioenriched ester derivatives 2– 4 afforded naproxen, ( S)- 1 , with no loss of enantiopurity.

Deracemization of alkyl diarylmethanes using (−)-sparteine or a chiral proton source

In a first stage, deracemization of 2-(1-phenylethyl)pyridine 1 and chlorpheniramine 2 was investigated in the presence of (−)-sparteine as a chiral ligand. Whereas ( R)-2-(1-phenylethyl)pyridine 1 was obtained in 65% ee with 2,6-di- tert-butyl-4-methylphenol as a proton donor, the opposite stereoselection was observed with EtOH leading to ( S)-2-(1-phenylethyl)pyridine 1 in 53% ee. A second methodology making use of (+)-( R)-1-[5-chloro-2-(methylamino)-phenyl]-1,2,3,4-tetrahydroisoquinoline 4 as a chiral proton source gave higher enantioselectivities, affording ( R)- 1 and ( R)- 2 in up to 84 and 75% ee, respectively.

ChemInform Abstract: First Synthesis of the Chiral Mixed O/S Ligands, 1,2‐Sulfinyl Thiols: Application as Chiral Proton Sources in Enantioselective Protonations of Enolates.

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.

Catalytic Enantioselective Protonation of Lithium Ester Enolates Generated by Conjugate Addition of Arylthiolate to Enoates.

A chiral ligand, a catalytic amount of lithium cation, and no chiral proton source: These are features of the present asymmetric addition-protonation of propenoates with 2-trimethylsilylbenzenethiol. The reaction is catalyzed by a combination of lithium 2-trimethylsilylbenzenethiolate and the chiral ligand 1. Desulfurization of the product affords 2-substituted propanoates with high ee values and without racemization. Furthermore, 1 can be recovered quantitatively for reuse.

Asymmetric Protonation of Lithium Enolate of α-Amino Acid Derivatives using Chiral Brønsted Acids

Chiral alcohols possessing an asymmetric 2-oxazoline ring were synthesized as new chiral Brønsted acids from tetrahydro-2-furoic acid and (1S,2R)-2-amino-1,2-diphenylethanol. These alcohols were superior to (S,S)- or (R,R)-imide reported previously as a chiral proton source for enantioselective protonation of lithium enolate of an alanine derivative.

Regio- and enantioselective synthesis of allenic esters by samarium(II)-mediated reduction of propargylic compounds through dynamic kinetic protonation

Regioselective synthesis of allenic esters was attained by SmI 2-mediated reduction of propargylic phosphates and ethers bearing alkoxycarbonyl groups at the acetylene terminus. Using suitable chiral proton source in this system, highly enantio-enriched allenic ester was obtained through dynamic kinetic resolution by Lewis acidic Sm(III)-mediated enantioselective protonation, even if starting with racemic propargylic phosphates.

Chiral sulfonamide induced enantioselective protonation of samarium enolate in the reaction of alpha,beta-unsaturated ester with ketone

Good enantioselectivity (up to 84% ee) has been achieved in the formation of alpha,gamma-substituted-gamma-butyrolactone by the SmI(2)-mediated reductive coupling of ketones with methyl methacrylate using various chiral proton sources.

First synthesis of the chiral mixed O/S ligands, 1,2-sulfinyl thiols: application as chiral proton sources in enantioselective protonations of enolates

A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.