Catalysis chiral base

The addition of an enolsilane to an aldehyde, commonly referred to as the Mukaiyama aldol reaction, is readily promoted by Lewis acids and has been the subject of intense interest in the field of chiral Lewis acid catalysis. Copper-based Lewis acids have been applied to this process in an attempt to generate polyacetate and polypropionate synthons for natural product synthesis. Although the considerable Lewis acidity of many of these complexes is more than sufficient to activate a broad range of aldehydes, high selectivities have been observed predominantly with substrates capable of two-point coordination to the metal. Of these, benzy-loxyacetaldehyde and pyruvate esters have been most successful. 

Okamura and coworkers151 studied the base catalyzed Diels-Alder reactions between 3-hydroxy-2-pyrone (224) and chiral l,3-oxazolidin-2-one based acrylate derivatives. Catalysis of the reaction between 224 and 225 by triethylamine gave fair to good de values, somewhat dependent on the solvent system used (equation 63, Table 7). Addition of 5% of water to the solvent isopropanol, for example, increased the de of the endo adduct 226 substantially. When the amount of water was increased, however, the triethylamine catalyzed reaction became less endo and diastereofacially selective, a small amount of exo 227 being obtained. Replacing triethylamine by the chiral base cinchonidine also improved the de, but now independently of the solvent system used. 

In this chapter, we discuss recent (reported mainly during 2000-2005) asymmetric reactions catalyzed by chiral bases. Because practicality is an important factor in the present asymmetric catalysis, we restricted our discussion mainly to the reactions giving over 90% ee unless the conversion is novel. We notice, however, that there are many potentially useful and scientifically interesting reactions, in which enantioselectivity does not exceed the practical range at this moment. Chiral organic base (proline and cinchona alkaloids)-catalyzed reactions were discussed in Chapter 11 by Lelais and MacMillan. 

Chiral base catalysis was classified into five sections and reviewed. Although the reactions described herein are promoted by Bronsted or Lewis bases, the Lewis acidic characteristics of metals play important roles in both substrate activation and enantioselection. Compared with chiral Lewis acid-catalyzed reactions,... 

In the case of chiral base catalysis of the E2 elimination, enantioenriched 7-hydroxyenones from the corresponding endoperoxides were obtained <2006JA12658> in fact, a one-pot asymmetric 1,4-dioxygenation of 1,3-cyclohepta-diene by sequential reaction with singlet oxygen and 5 mol% chiral catalyst provided the 7-hydroxyenones 80 in 90% yield and 92% ee (Scheme 18). 

Keywords Asymmetric synthesis, Chiral catalysis, Diversity-based approaches, Supported chiral catalysts, Solid-phase chemistry... 

In the Michael-addition, a nucleophile Nu is added to the / -position of an a,fi-unsaturated acceptor A (Scheme 4.1) [1], The active nucleophile Nu is usually generated by deprotonation of the precursor NuH. Addition of Nu to a prochiral acceptor A generates a center of chirality at the / -carbon atom of the acceptor A. Furthermore, the reaction of the intermediate enolate anion with the electrophile E+ may generate a second center of chirality at the a-carbon atom of the acceptor. This mechanistic scheme implies that enantioface-differentiation in the addition to the yfi-carbon atom of the acceptor can be achieved in two ways (i) deprotonation of NuH with a chiral base results in the chiral ion pair I which can be expected to add to the acceptor asymmetrically and (ii) phase-transfer catalysis (PTC) in which deprotonation of NuH is achieved in one phase with an achiral base and the anion... 

Catalytic, enantioselective addition of silyl ketene acetals to aldehydes has been carried out using a variant of bifunctional catalysis Lewis base activation of Lewis acids.145 The weakly acidic SiCU has been activated with a strongly basic phor-phoramide (the latter chiral), to form a chiral Lewis acid in situ. It has also been extended to vinylogous aldol reactions of silyl dienol ethers derived from esters. 

ESMS was employed to identify reactive intermediates in the enantioselective hydrogenation of ethyl pyruvate on Pt-alumina, Pt black, and Pt black+alumina catalysts modified by dihydrocinchonidine in acetic acid [56]. The ESMS spectra of the raw product revealed a large number of species which fell into four groups (1) dihydrocinchonidine and its hydrogenated derivatives (2) the adducts of ethyl pyruvate and its oligomers (3) (R)-ethyl lactate, the product of the enantioselective hydrogenation, and its adducts and (4) oxonium compounds formed from alumina. The latter most likely play a decisive role in the development of the chiral environment of the catalyst surface. As suggested by the authors, these oxonium cations could make the so-called electrostatic catalysis [57],based on electrostatic acceleration, possible. 

Two general reactions of this type are shown. There appears to be no report on stereoselective cyclizations of type a . Although transformation b has often been employed, e.g., for the construction of the chromanone skeleton 1, no stereoselective variants (simple diastereoselec-tion or enantioselection) appear to have been reported either. Since base catalysis has usually been applied, asymmetric induction by use of a chiral base catalyst appears feasible. However, this assumption still awaits experimental proof. 

Reist, M., Carrupt, P. A., Erancotte, E., Testa, B. Chiral inversion and hydrolysis of thalidomide mechanisms and catalysis by bases and serum albumin, and chiral stability of teratogenic metabolites. Chem. Res. Toxicol. 1998, 11, 1521-1528. 

The roots for the activity in the field of preparation of enantiopure amino acids in the Leibniz-Institut fur Organische Katalyse an der Universitat Rostock e.V. (formerly known as Bereich Komplexkatalyse which was a part of the Zentral-institut fur Organische Chemie der Akademie der Wissenschaften der DDR ) were planted at the end of the 1960s by Horst Pracejus, who was its director at that time (Fig. 1). In the 1950s Pracejus had previously worked on asymmetric catalysis and published outstanding results on the reaction of nucleophiles with ke-tenes catalyzed by chiral bases and developed a fundamental understanding of the mechanism of such enantioselective processes controlled by opposed entropic and enthalpic parts of the free activation enthalpy [1],... 

Figure 4. Molecular photochemical device prototype (a) and chiral metallacyclophane for asymmetric catalysis (b) based on bis(acetylide)Pt(II) compounds.

Tertiary amines have fotmd to be among the most useful chiral bases used in modem (asymmetric) catalysis. With respect to the chiral backbone of these catalysts, Cinchona alkaloids have emerged as the most commonly employed representatives and have proven their potential in numerous demanding applications 424, 443). 

Chiral base catalysis is one of the most versatile and broadly applicable types of catalysis. In particular, the potential of tertiary amines to act both as a base and as a nucleophilic catalyst makes chiral tertiary amines like Cinchona alkaloids a privileged catalyst structure in modem synthesis chemistry. In addition, the field of achiral phosphine and carbene catalysis has proven its potential in numerous applications in the past and it is probably only a matter of time until chiral phosphines and carbenes will also be used routinely for other presently demanding natural product total synthesis (Table 7). 

Building upon these concepts, this chapter firstly gives an insight into the modes of action of a selection of non-covalent chiral organocatalysts, employing chiral Brpnsted acid catalysis, chiral Brpnsted base catalysis, and chiral phase-transfer catalysis (PTC). Further sections of this chapter describe two separate case studies that aim to compare and contrast selected covalent and non-covalent strategies for achieving two distinct processes, acyl transfer reactions and asymmetric pericyclic processes. 

Scheme 1.1 Use of chiral bases and phase-transfer catalysis in Michael reactions.

Brpnsted) base functionality as the sole catalytically active group as well as those having an alternative H-bond donor like a hydroxy group (e.g., cinchona alkaloids) have found widespread applications in asymmetric catalysis [88]. The potential of these catalysts is due to the fact that a variety of different activation modes are possible, thus facilitating their application for different types of reactions. On the one hand, chiral (Brpnsted) bases can be used to carry out face-selective deprotonations and the formarion of chiral ion pairs, but, on the other hand, chiral (Lewis) bases can also be used as nucle-ophiUc catalysts, which represent a very important application field of chiral base catalysts. 

While asymmetric counteranion-directed catalysis (ACDC) has been estab-hshed as a powerful strategy in iminium catalysis, enamine-based asymmetric counteranion-directed catalysis has not yet been developed. Recently, Lu et al. [32] demonstrated that the combination of a cinchona alkaloid-derived primary amine and chiral camphorsuhnnic acid (CSA) results in an effective ion-pair catalyst for the directed asymmetric amination of a-branched aldehydes through enamine activation (Scheme 43.21). 

Wanner et al. developed an efficient Pictet-Spengler reaction of secondary amines and aldehydes via the formation of active sulfenyliminium ions in situ from N-sulphenyltryptamine 16, catalyzed by chiral Brpnsted acids 5d (Scheme 2.6b) [9a], The enantioselectivity may be delivered from asymmetric counterion-directed catalysis [9a], Based on a similar strategy, they achieved the total synthesis of (+)-yohimbine via a phosphoric acid-catalyzed Pictet-Spengler reaction, which employed an A -(5-oxy-2,4-pentadienyl)tryptamine derivative and methyl 5-oxo-2(phenylseleno)pentanoate as starting materials [9b],... 

Graf C-D, Malan C, Harms K, Knochel P. New homochiral ligands bearing nonstereogenic chirotopic centers. Lithiated N,N -dialkylureas as chiral bases and sterically crowded phosphines for asymmetric catalysis. J. Org. Chem. 1999 64 (15) 5581-5588. 

The mechanism of the hydrogenation of a,j -unsaturated carboxylic acids by chiral ruthenium BINAP complexes has been investigated (Scheme 5). The rate-limiting step in methanol at near-ambient temperature is the activation of H2 to give a anionic hydrido complex. The reaction is sensitive to strong acids one equivalent CF3SO3H per Ru prevents catalysis, while base has no effect. Over 90% enantiomeric excess (ee) was achieved. ... 

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