Enantioselective chiral acid

To the best of our knowledge the data in Table 3.2 constitute the first example of enantio selectivity in a chiral Lewis-acid catalysed organic transformation in aqueous solution. Note that for the majority of enantioselective Lewis-acid catalysed reactions, all traces of water have to be removed from the... 

Giovanni Boocaletti is gratefully acknowledged for the large number of experiments that paved the way to enantioselective Lewis-acid catalysis in water. Furthermore, we kindly thank the Syncom company for the use of the chiral HPLC column. 

The most effective catalysts for enantioselective amino acid synthesis are coordination complexes of rhodium(I) with 1,5-cyclooctadiene (COD) and a chiral diphosphine such as (JR,jR)-l,2-bis(o-anisylphenylphosphino)ethane, the so-called DiPAMP ligand. The complex owes its chirality to the presence of the trisubstituted phosphorus atoms (Section 9.12). 

The complex obtained from commercially available chiral a-amino acids (AA) with Cu + ion induces asymmetry in the Diels-Alder reaction of 31 (R = H) with 32. By using 10% Cu(II)-AA (AA = L-abrine) the cycloaddition occurs e/iJo-stereoselectively in 48 h at 0°C with high yield and with acceptable enantioselectivity ee = 1A%). This is the first example of enantioselective Lewis-acid catalysis of an organic reaction in water [9b]. 

The enantioselective hydrogenation of a,fj- or / ,y-unsaturated acid derivatives and ester substrates including itaconic acids, acrylic acid derivatives, buteno-lides, and dehydrojasmonates, is a practical and efficient methodology for accessing, amongst others, chiral acids, chiral a-hydroxy acids, chiral lactones and chiral amides. These are of particular importance across the pharmaceutical and the flavors and fragrances industries. 

Bidentate chiral water-soluble ligands such as (S,S)-2,4-bis(diphenyl-sulfonatophosphino)butane BDPPTS (Fig. 2) or (R,R) 1,2-bis(diphenylsul-fonatophosphinomethyl)cyclobutane have been prepared [25]. Their palladium complexes catalyze the synthesis of chiral acids from various viny-larenes and an ee of 43% has been reached for p-methoxystyrene with the BDPPTS ligand. Furthermore, recycling of the aqueous phase has shown that the regio- and enantioselectivity are maintained and that no palladium leaches. 

FIGURE 1.3 Enantiomer separation of the chiral acid iV-acetyl-a-allyl-glycine on CHIR-ALPAK QN-AX (a) and CHIRALPAK QD-AX (b) by an enantioselective anion-exchange retention process. Chromatographic conditions Column dimension, 150 x 4 mm ID eluent, 1 % (v/v) glacial acetic acid in methanol flow rate, 1 mLmin temperature, 25°C detection, UV 230 nm. (Reproduced from M. Lammerhofer, et ah, Nachrichten aus der Chemie, 50 1037 (2002). With permission.)... 

Overall, the /er/-butyl carbamates of quinine and quinidine evolved as the most effective chiral selectors among this family because of their broad enantioselectivity spectmm and exceptional degree of selectivity for a wide variety of chiral acids. On... 

These enantioselective capillary columns showed extremely good performance in the CEC mode. Plate numbers in excess of 100,000 m could be easily achieved for a variety of amino acid derivatives (with chromophoric and fluorophoric labels) (Eigure 1.34a) as well as other chiral acids such as 2-aryloxycarboxylic acids. 

Enantioselective, Chiral Pool-Based Syntheses of Paraconic Acids. 49... 

Enantioselective, Chiral Auxiliary Based Syntheses of Paraconic Acids 2.3.1... 

Later, Corey reported that the bulky superacid triflylimide (Tf2NH) protonates chiral oxazaborolidines to form superactive, stable, chiral acids 11a and 11b, which are highly effective catalysts for a wide variety of enantioselective Diels-Alder reactions that were beyond the reach of synthetic chemists (Scheme... 

Until 2006, a severe limitation in the field of chiral Brpnsted acid catalysis was the restriction to reactive substrates. The acidity of BINOL-derived chiral phosphoric acids is appropriate to activate various imine compounds through protonation and a broad range of efficient and highly enantioselective, phosphoric acid-catalyzed transformations involving imines have been developed. However, the activation of simple carbonyl compounds by means of Brpnsted acid catalysis proved to be rather challenging since the acid ity of the known BINOL-derived phosphoric acids is mostly insufficient. Carbonyl compounds and other less reactive substrates often require a stronger Brpnsted acid catalyst. 

Liu et al. 43) prepared chiral BINOL ligands bearing dendritic Frechet-type polybenzyl ether wedges ((J )-41-(J )-44), which were assessed in enantioselective Lewis acid-catalyzed addition of Et2Zn to benzaldehyde. 

METAL-FREE REDUCTION OF IMINES ENANTIOSELECTIVE BR0NSTED ACID CATALYZED TRANSFER HYDROGENATION USING CHIRAL BINOL-PHOSPHATES AS CATALYSTS... 

It is significant that the reaction mixture was worked up by removal of the unreacted ester by hexane extraction and concentration of the aqueous layer to obtain the desired (i )-amino acid. The process has a high throughput and was easy to handle on a large scale. However, because of the nature of a batch process, the enzyme catalyst could not be effectively recovered, adding significantly to the cost of the product. In the further scale up to 100-kg quantity productions, the resolution process was performed using Sepracor s membrane bioreactor module. The enzyme was immobilized by entrapment into the interlayer of the hollow-fiber membrane. Water and the substrate amino ester as a neat oil or hexane solution were circulated on each side of the membrane. The ester was hydrolyzed enantioselectively by the enzyme at the membrane interface, and the chiral acid product... 

Chiral Bronsted acids can also promote the asymmetric addition of allylic tin reagents to carbonyl compounds. Baba and coworkers have found that a stoichiometric amount of (fl)-BINOL (37) acts a chiral promoter for the allylation of unactivated ketones with tetraallyltin and in the presence of MeOH, the corresponding nonracemic tertiary homoallylic alcohols are obtained with up to 60% ee [50]. Later, Woodward et al. improved this process and achieved a catalytic enantioselective allylation of aryl ketones by employing (fl)-monothio-binaphthol 36 as a chiral Bronsted catalyst [49]. For instance, in the presence of 20 mol% of the chiral acid 36 and 40 mol% of H20 in toluene, acetophenone (42) was allylated by a 0.7 0.3 mixture of tetraallyltin (41) and butyltriallylltin (55) to give the (jR)-enriched allylated product 56 almost quantitatively with 89-86% ee (Scheme 8). 

Our research group developed catalytic enantioselective protonations of preformed enolates of simple ketones with (S,S)-imide 23 or chiral imides 25 and 26 based on a similar concept [29]. For catalytic protonation of a lithium eno-late of 2-methylcyclohexanone, chiral imide 26, which possesses a chiral amide moiety, was superior to (S.S)-imide 23 as a chiral acid and the enolate was pro-tonated with up to 82% ee. 

Enantioselective reactions have also been reported for the hydrolysis of enamines containing a chiral amine moiety via protonation or of prochiral enamines by the use of a chiral acid. Other asymmetric reactions are summarized in an excellent review by Seebach and coworkers179 and by Oare and Heathcock193. 

Maruoka K, Ooi T (2003) Enantioselective amino acid synthesis by chiral phase-transfer catalysis. Chem Rev 103 3013-3028... 

New Developments in Enantioselective Bronsted Acid Catalysis Chiral Ion Pair Catalysis and Beyond... 

First Highly Enantioselective Br0nsted Acid Catalyzed Strecker Reaction Use of C-Nucleophiles in Chiral Ion Pair Catalysis... 

The possibility of using C-nucleophiles in chiral ion pair catalysis encouraged us to investigate an enantioselective Brpnsted acid catalyzed imino ene reaction (Rueping et al. 2007a Scheme 5). The reaction consists of a new BINOL-phosphate catalyzed addition of methylene-hydrazines 22 to A-Boc-protected aldimines 23 to afford chiral amino-hydrazones 24. 

The enantioselective Brpnsted acid catalyzed activation of a pure carbonyl compound using a chiral BINOL-phosphate had not previously been described. Hence, we decided to develop such a reaction, a so far unprecedented Brpnsted acid catalyzed enantioselective Nazarov cy-clization (Rueping et al. 2007c). 

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