Ketopinic Acid Research Articles

Hydroxyamide-catalyzed enantioselective addition of diethylzinc to benzaldehyde in the absence of titanium

Three camphor-based tertiary-amido isoborneols have been obtained from ketopinic acid and tested as ligands for the hydroxyamide-catalyzed enantioselective addition of diethylzinc to benzaldehyde in the absence of Ti(O- i-Pr) 4. The results obtained have been compared with previous results published by Oppolzer. The new chiral ligands showed effective asymmetric activity in the absence of titanium (up to 98% yield and 90% ee). It is demonstrated that non-bulky dialkylamino groups are necessary for obtaining high chemical yields, whereas the C 2 symmetry is necessary to reach a good enantioselection level.

ChemInform Abstract: New Chiral Hydroxyoxazolines Based on Ketopinic Acid and Their Use in the Asymmetric Diels—Alder Reaction.

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.

N/N/O versus N/O/O and N/O amino isoborneols in the enantioselective ethylation of benzaldehyde

Enantiopure 10-(4-methylpiperazin-1-yl)isoborneol, a N/N/O-tridentate chiral diamino isoborneol, has been obtained from enantiopure ketopinic acid and its catalytic activity (as chiral ligand in the enantioselective addition of diethylzinc to benzaldehyde) measured and compared with the previously reported data for related N/N/O, N/O/O, and N/O isoborneols. It is demonstrated that the pentacoordinated-zinc Oppolzer’s model for transition states is useful for explaining the catalytic behavior of N/N/O-tridentate ligands. In such cases, stable syn- or anti-type transition states can be proposed depending on the catalyst’s conformational flexibility.

New Chiral Hydroxyoxazolines Based on Ketopinic Acid and Their Use in the Asymmetric Diels-Alder Reaction

Several chiral hydroxyoxazolines have been prepared starting from (1 S)-(+)-ketopinic acid and enantiopure β-amino -alcohols by short synthetic routes. They have been employed in the catalytic asymmetric Diels-Alder reaction, resulting in ee values of up to 90%.

Enantioselective Henry reaction catalyzed with copper(II)–iminopyridine complexes

Copper complexes of chiral iminopyridines prepared from camphane-derived ketones and picolylamine catalyzed the enantioselective Henry (nitroaldol) reaction between nitromethane and a number of aromatic and aliphatic aldehydes with high yields and good enantioselectivities. Iminopyridines derived from (1 R)-(+)-camphor and (1 S)-(+)-ketopinic acid gave the best results to afford the opposite enantiomers in each case, despite the fact they have the same stereochemical pattern at the camphane skeleton. The reactions were carried out without air or moisture exclusion.

Ketopinic acid and diisoproylideneketogulonic acid as chiral ion-pair selectors in capillary electrophoresis: Enantiomeric impurity analysis of S-timolol and 1 R,2 S-ephedrine

1 S,4 R-(+)-ketopinic acid [(+)-KPA] has been introduced as a chiral selector for the separation of pharmacologically active amines by non-aqueous capillary electrophoresis (NACE). (+)-KPA gave enantioresolution for most of the compounds previously separated by 2 R,3 S,4 R,5 S-(−)-2,3:4,6-di- O-isopropylidene-2-keto- l-gulonic acid [(−)-DIKGA], but with a reversed migration order. A complete enantioresolution (Rs = 4.2) was obtained for timolol, a compound that could not be resolved using (−)-DIKGA as the selector. Thus, (+)-KPA was evaluated for the enantiomeric purity determination of S-timolol. A method based on pre-concentration by transient isotachophoresis (tITP) provided a limit of detection (LOD) of 0.2% R-timolol in S-timolol samples. Because of the lack of enantioresolution of ephedrine when (+)-KPA was used as the selector, a method with (−)-DIKGA has been developed and validated for determination of the enantiomeric purity of the 1 R,2 S enantiomer. The method gave good precision and accuracy with an LOD (S/N = 3) of 0.033% for the enantiomeric impurity 1 S,2 R-ephedrine.

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by (1R,2R)‐10‐(Dialkylamino)isoborneols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Development of β‐Hydroxyamide/Titanium Complexes for Catalytic Enantioselective Silylcyanation of Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by (1R,2R)-10-(Dialkylamino)isoborneols

(1R,2R)-10-Dialkylaminoisoborneols, γ-amino alcohol-type ligands, were synthesized from (+)-ketopinic acid. Their catalytic ability as a chiral ligand for enantioselective addition of diethylzinc to aldehydes was evaluated. Among them, the ligand with a 9-azabicyclo[3.3.1]nonan-9-yl group as an amino moiety was the most effective and showed good enantioselectivity towards various aldehydes.

Development of β-hydroxyamide/titanium complexes for catalytic enantioselective silylcyanation of aldehydes

A highly enantioselective addition of trimethylsilylcyanide to aldehydes catalyzed by chiral titanium complexes is described. The chiral titanium complexes were prepared in situ from Ti(O i Pr) 4 and β-hydroxyamide ligands, that could easily be synthesized from ketopinic acid and C 2 symmetrical chiral diamines in a small number of steps.

Chiral Lewis Acid Catalyzed Asymmetric Baylis—Hillman Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 7‐anti‐Bromo‐3,3‐dimethyl‐2‐oxonorbornane‐1‐carboxylic Acid: A New Chiral Source from the Chiral Pool.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chiral Lewis acid-catalyzed asymmetric Baylis-Hillman reactions.

An effective chiral Lewis acid-catalyzed asymmetric Baylis-Hillman reaction is described. Good to high enantioselectivities were obtained using 3 mol % chiral catalyst. Novel camphor-derived dimerized ligands were prepared from the condensation of (+)-ketopinic acid with the corresponding diamines and hydrazine under acidic conditions. When alpha-naphthyl acrylate was used as a Michael acceptor, the reaction is complete within 20 min with high stereoselectivity and in reasonable chemical yields.

Synthesis of 7- anti-bromo-3,3-dimethyl-2-oxonorbornane-1-carboxylic acid: a new chiral source from the chiral pool

Enantiopure 7- anti-bromo-3,3-dimethyl-2-oxonorbornane-1-carboxylic acid, an interesting new chiral norbornane-1-carboxylic acid analogous to the well known chiral-source ketopinic acid, has been obtained for the first time from commercially available 3- endo-bromocamphor. The synthesis takes place enantiospecifically in four straightforward synthetic steps with high overall yield. The established route constitutes a model procedure for the preparation of other chiral C(7)-substituted 3,3-dimethyl-2-oxo-norbornane-1-carboxylic-acid-derived chiral sources (e.g. tridentate chiral ligands) from camphor.

Chiral Mitsunobu reactions with (1 S)-(+)-ketopinic acid: kinetic resolutions of secondary alcohols

Several secondary alcohols undergo the Mitsunobu reaction with triphenylphosphine, diethyl azodicarboxylate and (1 S)-(+)-ketopinic acid (0.5 equiv. each relative to alcohol) in CH 2Cl 2 solution at −23°C, to furnish the chiral secondary alcohol and its ketopinate ester (d.e. >95%). Chromatographic separation of these and subsequent hydrolysis of the ketopinate ester (KOH/EtOH/0°C) provides the chiral secondary alcohol in overall yields of ∼75% and e.e. of ∼80%. When the above Mitsunobu reaction is performed with 1 equiv. of all the reactants, an effective dynamic kinetic resolution of the alcohol is observed in two cases, the ketopinate esters being isolated in 63 and 75% yields and >95% d.e.

Palladium-catalyzed asymmetric Diels–Alder reactions with novel chiral imino-phosphine ligands

Palladium-catalyzed asymmetric Diels–Alder reactions have been achieved with considerably high enantioselectivity by using chiral imino-phosphine ligands derived from (1 S,4 R)-(+)-fenchone, (1 R,2 R,5 R)-(+)-2-hydroxy-3-pinanone derivatives, (1 S,5 R)-(−)-menthone, (1 R,4 R)-(+)-camphor, and (1 S)-(+)-ketopinic acid. A mechanism for the asymmetric induction is proposed on the basis of the stereochemical outcome of the reactions.

ChemInform Abstract: Chiral P,N‐Ligands Based on Ketopinic Acid in the Asymmetric Heck Reaction

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.

Chiral P,N-ligands based on ketopinic acid in the asymmetric Heck reaction.

[figure: see text] Novel chiral P,N-ligands were synthesized from (1S)-(+)-ketopinic acid using palladium-catalyzed coupling reaction of a vinyl triflate and either a diarylphosphine or a dialkylphosphine as the key step. Palladium complexes of these ligands are efficient catalysts for asymmetric Heck reaction between aryl or alkenyl triflates and cyclic alkenes. Products were obtained with good to excellent enantioselectivity from arylation and alkenylation of 1,2-dihydrofuran, cyclopentene, and 4,7-dihydro-1,3-dioxepin.

ChemInform Abstract: Asymmetric Hydrogenation of Dehydroamino Acid Derivatives Catalyzed by a New Aminophosphine Phosphinite Ligand Derived from Ketopinic Acid.

ChemInform 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.

Asymmetric hydrogenation of dehydroamino acid derivatives catalyzed by a new aminophosphine phosphinite ligand derived from ketopinic acid

A new chiral aminophosphine phosphinite N,O-bis(diphenylphosphino)-(1S,2R)-1-(N-methylamino) methyl-2-hydroxyl-7,7-dimethylbicyclo[2.2.1]heptane was synthesized from ketopinic acid and its application to the asymmetric hydrogenation of dehydroamino acid derivatives examined.