Chiral catalysts, structure

The first reported chiral catalysts allowing the enantioselective addition of diethylzinc to aryl aldehydes in up to 60% cc were the palladium and cobalt complexes of 1,7,7-trimethylbicy-clo[2.2.1. ]heptane-2,3-dione dioxime (A,B)3. A number of other, even more effective catalysts, based on the camphor structure (C K, Table 26) have been developed. 

To obtain information about the structural requirements of a ligand capable of catalyzing the addition of dialkylzincs to aldehydes, various simple amines, alcohols and amino acid derived amino alcohols were tested as chiral catalysts (Table 27). 

The transition state assembly 55 (Figure 3.8), that rationalizes the stereochemistry of the cycloadduct, is consistent with the structure of the chiral catalyst determined by an X-ray diffraction study. Interestingly it has been shown [58] that in the cycloadditions of maleimides 56 with 2-methoxy-l,3-butadiene, the enantioselection depends on the bulkiness of Ar and Ari groups of catalyst 54 and dienophile 56, respectively (Scheme 3.13). The importance of the bulky Ari... 

In the last 20 years a great deal of effort has been focused towards the immobilization of chiral catalysts [2] and disparate results have been obtained. In order to ensure the retention of the valuable chiral hgand, the most commonly used immobihzation method has been the creation of a covalent bond between the ligand and the support, which is usually a solid, hi many cases this strategy requires additional functionalization of the chiral hgand, and this change - together with the presence of the very bulky support - may produce unpredictable effects on the conformational preferences of the catalytic complex. This in turn affects the transition-state structures and thus the enantioselectivity of the process. 

The photochemical behaviour of 7 OEt is the first example in which the reaction of achiral molecules in an achiral crystal packing does not occur at random but stereospecifically, resulting in a syndiotactic structure. As no external chiral catalyst exists in the reaction, the above result is a unique type of topochemical induction , which is initiated by chance in the formation of the first cyclobutane ring, but followed by syndiotactic cyclobutane formation due to steric repulsions in the crystal cavity. That is, the syndiotactic structure is evolved under moderate control of the reacting crystal lattice. 

The lesson from this case is that reactions that are quite unselective under simple Lewis acid catalysis can become very selective with chiral catalysts. Moreover, as this particular case also shows, they can be very dependent on the specific structure of the catalyst. 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Chirality at surfaces can be manifested in a number of forms including the intrinsic chirality of the surface structure and even the induction of chirality via the adsorption of achiral molecules onto achiral surfaces. The ability of STM to probe surfaces on a local scale with atomic/molecular resolution has revolutionized the understanding of these phenomena. Surfaces that are globally chiral either due to their intrinsic structure or due to the adsorption of chiral molecules have been shown by STM to establish control over the adsorption behavior of prochiral species. This could have profound consequences for the understanding of the origin of homochirality in life on Earth and in the development of new generations of heterogeneous chiral catalysts that may, finally, make a substantial impact on the pharmaceutical industry. 

Enantioselective cyclopropanation of monoolefins 214 has also been performed. With the already mentioned chiral catalysts 195a and 209-213 rather high enantiomeric excess was achieved in some cases (Table 16), and the vinylcyclopropane structure was obtained in a subsequent dehydrohalogenation step. 

Because of the separation of this chapter into fundamental synthetic and structural aspects of organozinc compounds and the applications of these compounds in organic synthesis, many topics are treated twice, but with decidedly different emphases. By way of example, the important organozinc alkoxides are covered first in the inorganometallic section, where the emphasis is on their syntheses, structures, and applications other than in organic synthesis. Later, in Section 2.06.16.2, the uses of such compounds as chiral catalysts in asymmetric addition reactions are discussed. 

Since the discovery of amino alcohol induced dialkylzinc addition to aldehydes, many new ligands have been developed. It has recently been reported that chiral amino thiols and amino disulfides can form complexes or structurally strained derivatives with diethylzinc more favorably than chiral amino alcohols and thus enhance the asymmetric induction. Table 2 15 is a brief summary of such chiral catalysts. 

Wang et al.36 have used the chiral catalyst (DHQ)2 PHAL (see Chapter 4 for the structure) for the asymmetric synthesis of the taxol side chain. Optically enriched diol was obtained at 99% ee via asymmetric dihydroxylation. Sub-... 

Scheme 6.35. Zr-catalyzed enantioselective addition of Danishefsky dienes to o-hydroxyphenylimines the structure of the purported chiral catalyst (89) is also shown.

A major advantage that nonenzymic chiral catalysts might have over enzymes, then, is their potential ability to accept substrates of different structures by contrast, an enzyme will select only its substrate from a mixture. Striking examples are the chiral phosphine-rhodium catalysts, which catalyze die hydrogenation of double bonds to produce chiral amino acids (10-12), and the titanium isopropoxide-tartrate complex of Sharpless (11,13,14), which catalyzes the epoxidation of numerous allylic alcohols. Since the enantiomeric purities of the products from these reactions are exceedingly high (>90%), we might conclude... 

Corey and colleagues215 prepared chiral aluminum complexes from chiral bis(sulfona-mides) and trimethylaluminum. These were successfully applied in the cycloadditions of 3-acryloyl-l,3-oxazolidin-2-one (17a) with substituted cyclopentadienes. Thus, the reaction of 3-acryloyl-l,3-oxazolidin-2-one with 5-(benzyloxymethyl)cyclopentadiene (331) afforded 332 with 94% ee (equation 93). A transition state was proposed based on the X-ray structure of the chiral catalyst and on NMR data of the 1 1 complex between 333... 

Concurrent with studies on cyclometalation, studies on the effects of the structure of phosphoramidite ligand had been conducted. Several groups studied the effect of the stmcmre of ligand on the rate and selectivity of these iridium-catalyzed allylic substitutions. LI contains three separate chiral components - the two phenethyl moieties on the amine as well as the axially chiral BINOL backbone. These portions of the catalyst structure can control reaction rates by affecting the rate of cyclometalation, by inhibiting catalyst decomposition, or by forming a complex that reacts faster in the mmover-limiting step(s) of the catalytic cycle. 

Significant progress has been witnessed in asymmetric catalysis/ In conventional asymmetric catalysis, the asymmetric catalyst C provides the enantioenriched product P, whose structures are generally different from those of the asymmetric catalysts. In contrast, asymmetric autocatalysis is an automultiphcation of a chiral compound P, in which the chiral product P acts as a chiral catalyst P for its own production/ ... 

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