Dimeric cinchona alkaloid catalyst

Scheme 13.8 summarized kinetic resolution of the 5-oIfcyI-l,3-dixolane-2,4-diones roc-15 by alcoholysis in the presence of the dimeric cinchona alkaloid catalyst 11, (DHQD)2AQN, as reported by Tang and Deng [19]. These authors observed that the related 5-oryl-l,3-dioxolane-2,4-diones 29 (Scheme 13.12) underwent rapid rac-emization under the reaction conditions used, thus enabling dynamic kinetic resolution. This difference in reactivity was attributed to the higher acidity of the a-CH... 

Scheme 13.9 summarized kinetic resolution of N-urethane protected N-carboxy anhydrides rac-18 by methanolysis in the presence of the dimeric cinchona alkaloid catalyst 11, (DHQD)2AQN, as reported by Deng et al. [20]. These kinetic resolutions were typically conducted at low temperature - from —78 to —60 °C. Deng et al. later observed that if the reaction temperature was increased racemization of the starting aryl N-carboxy anhydrides rac-18 becomes sufficiently rapid to enable a dynamic kinetic resolution [21]. Configurational stability of the product esters... 

The condensation reaction of (3-dicarbonyl compounds with a-haloketones to generate hydroxydihydrofuran is known as an interrupted Feist-Benary reaction. Calter et al. reported an enantioselective version of this reaction [26]. The aldol reaction of diketone with a-bromo-a-ketoester followed by cyclization proceeded in the presence of dimeric cinchona alkaloid catalyst to give cyclized product in high yield with high ee... 

The desymmetrization method was applied for the asymmetric synthesis of (+)-biotin [78] and the y-amino acid baclofen [79]. Furthermore, Deng et al. reported the kinetic resolution of cyclic anhydrides of p,y-unsaturated a-amino acids in the presence of the dimeric cinchona alkaloid catalyst (DHQD)jAQN 68a (10 mol%)... 

Pt/Al2C>3-cinchona alkaloid catalyst system is widely used for enantioselective hydrogenation of different prochiral substrates, such as a-ketoesters [1-2], a,p-diketones, etc. [3-5], It has been shown that in the enantioselective hydrogenation of ethyl pyruvate (Etpy) under certain reaction conditions (low cinchonidine concentration, using toluene as a solvent) achiral tertiary amines (ATAs triethylamine, quinuclidine (Q) and DABCO) as additives increase not only the reaction rate, but the enantioselectivity [6], This observation has been explained by a virtual increase of chiral modifier concentration as a result of the shift in cinchonidine monomer - dimer equilibrium by ATAs [7],... 

The development of dimeric cinchona alkaloids as very efficient and practical catalysts for asymmetric alkylation of the N-protected glycine ester 18 was reported... 

The highest enantioselectivity (up to >99%) yet achieved in the addition of S-nucleophiles to enones was reported in 2002 by Deng et al. [59]. By systematic screening of monomeric and dimeric cinchona alkaloid derivatives they identified the dihydroquinidine-pyrimidine conjugate (DHQD PYR (72, Scheme 4.35) as the most effective catalyst. This material is frequently used in the Sharpless asymmetric dihydroxylation and is commercially available. Screening of several aromatic thiols resulted in the identification of 2-thionaphthol as the nucleophile giving best yields and enantioselectivity. Examples for the (DHQD PYR-catalyzed addition of 2-thionaphthol to enones are summarized in Scheme 4.35. 

Quite remarkable progress has also been achieved in enantioselective transformation of cyclic anhydrides derived from a-hydroxy and a-amino carboxylic acids. By careful choice of the reaction conditions, dynamic kinetic resolution by alcoholysis has become reality for a broad range of substrates. Again, the above mentioned dimeric cinchona alkaloids were the catalysts of choice. In other words, organoca-talytic methods are now available for high-yielding conversion of racemic a-hydroxy and a-amino acids to their enantiomerically pure esters. If desired, the latter esters can be converted back to the parent - but enantiomerically pure - acids by subsequent ester cleavage. 

Soon after, the same research group found that dimeric cinchona alkaloids such as (DHQ)2AQN (125) and (DHQD)2PHAL (33) can also be used as highly enantioselective organic Lewis base catalysts for the cyanosilylation of acetal ketones (131,... 

Figure 6.1 Two examples of dimeric cinchona alkaloid-based Bronsted base catalysts.

More detailed structure-selectivity studies and study of in j/tw-formed CBPTC were reported by Lygo et al. [12]. Shortly afterward based on the above-mentioned findings, other more efficient CBPT catalysts were developed and studied. In 2001, Jew et al. [13] prepared the dimeric Cinchona alkaloid ammonium salts III-V (Scheme 8.1) to enhance catalytic efficiency by the dimerization effect. The highest catalytic activity in the alkylation of 1 was observed with the mcto-dimeric catalyst derived from xylene IV when the corresponding alkylated products were obtained with excellent enantiomeric excess (90-99% ee). 

In the dimerization of mono substituted ketenes in the presence of a cinchona alkaloid catalyst the symmetric dimers are obtained with an e,e of 91-97 %... 

Tertiary Amines It is significant to note that in both Pracejus asymmetric ketene alcoholysis and Wynberg s ketene-chloral cycloaddition, the catalysts of choice were both members of the cinchona alkaloid family that promoted the desired asymmetric process in remarkably high levels of stereocontrol. In 1996, Calter reported a catalytic, asymmetric dimerization of methylketene 89 using cinchona alkaloid catalysts to afford enantiomerically enriched (3-lactones 90 that were reduced in situ using lithium aluminum hydride (LiAlH4) to afford l-hydroxy-3-ketones 91 (Scheme 3.20) [54]. 

Inspired by the positive effect of dimeric cinchona alkaloid ligands in the Sharpless asymmetric dihydroxylation [55], Jew, Park, and coworkers developed a new family of dimeric cinchona-derived catalysts. The authors first prepared a series of dimeric cinchonidinium salts 24, 25a, and 26 using a phenyl spacer (Figure 12.7)... 

The probable structure of the 1,3-phenyl-dimeric catalyst 4 is shown in Figure 4.7. This is based on the results of an X-ray crystallographic study in which the conformation of the two cinchona alkaloid units are placed in a direction of anti-relationship to each other. The figure also shows that each cinchona alkaloid unit... 

Jew and Park have also utilized the dimerization effect, as observed in the development of Sharpless asymmetric dihydroxylation, where ligands with two independent cinchona alkaloid units attached to heterocyclic spacers led to a considerable increase in both the enantioselectivity and scope of the substrates, to design dimeric and trimeric cinchona alkaloid-derived phase-transfer catalysts 12 [12] and 13 [13]. These authors investigated the ideal aromatic spacer for optimal dimeric catalysts, and found that the catalyst 14 with a 2,7-bis(bromomethyl) naphthalene spacer and two cinchona alkaloid units exhibited remarkable catalytic and chiral efficiency (Scheme 11.3) [14]. 

Some systems of different structure have shown their ability to catalyze the formation of a new carbon-carbon bond by reaction of two ketones. The enantioselective aldol reaction between 1,3-cyclohexanedione (173) and different a-bromoketo esters 174 followed by final cyclization gave as the main compound cw-configured 176. Several Cinchona alkaloid derivatives were tested in this transformation, with the dimeric catalyst system 175 in the presence of a proton sponge and an ammonium salt affording the best results (Scheme 4.37) [256], Also dimeric cinchona... 

Very recently, the same researchers also discovered the potential of variation at the CS-vinyl moiety of the Cinchona alkaloid and performed Mizoroki-Heck coupling reactions between the Cinchona alkaloid-derived dimer and di-iodide, affording the chiral polymer PTC 14d (henzylation, 95% enantiomeric excess). The insolubility of the polymer makes it possible to recover the catalyst from the reaction mixture and recycle it several times without a decrease in the chemical yield or enantioselectivity (Scheme 16.9). ... 

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