Cinchona substrates structures

The influences of catalyst preparation, modifler and substrate structure, of various additives, and of reaction parameters have been reported for both the tartrate modifled Ni catalysts [2,4,11 ] as well as for Cinchona modifled Pt catalysts [2, 3, 7]. In addition, kinetic [2, 4,12,13] and molecular modeling studies [8] have been carried out. This experimental basis allows the discussion of their mode of action with some confidence and a mechanistic picture has been developed in the last few years that can explain the major observations, even though it is not accepted universally. 

Several studies have been reported on the mechanism of chiral catalysis by modified solid catalysts. Both modifier and substrate structures play important roles. Refer to reviews by Fish and Ollis (1978), Izuma (1983), Sachtler (1985), Tai and Harada (1986), and Blaser et al. (1988) for details of various postulated mechanisms, but one particular conclusion is significant. For the cinchona-modified platinum catalyst, the presence of nitrogen is considered essential, and the configuration at Cg of the alkaloid determines which enantiomer of the product is formed. 

The overall steric demands of the catalyst and the substrate are important in the spatial arrangement of the H-bonded complex. Consequently, although the less rigid ephedrinium salts have been used with some success, they are generally less effective than the derivatives of the cinchona alkaloids, the rigidity of which imposes a greater stereochemical restraint on the structure of the H-bonded complexes. 

FIGURE 18.6 Structures of good, medium, and bad substrates for cinchona-modified Pt catalysts. 

Concerning the stereochemical course of this reaction, Wynberg has proposed a mechanism based mainly on kinetic measurements and structures of substrates in pioneering work on the asymmetric thiol addition catalyzed by cinchona alkaloids. In our case, various sterically modified analogs of the base catalyst are readily achievable, and elucidation of the mechanism appears mainly dependent on the effects of the structure of the catalyst on the optical yields. From the experimental results, three notable points must be taken into consideration, namely,... 

Scheme 12.4 Structures of good (upper), medium (center) and bad (lower) substrates for cinchona-modified catalysts.

Chiral Br0nsted base catalysis began with the recognition of a natural product class of compounds in the cinchona alkaloid family [2]. Cinchona alkaloids are templates for Br0nsted bases when their quinuclidine nitrogen is protonated by nucleophilic substrates, resulting in a stabilized chiral intermediate for stereochemical attack of an electrophile. Systematic evaluahon of structural variants to the scaffold... 

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