Cinchona catalysts Bronsted bases

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

Two examples of hetero-Michael reactions have been reported using these kinds of bis-cinchona alkaloid-based chiral Bronsted bases as catalysts. One of them refers to a sulfa-Michael reaction and the other is a case of an aza-Michael reaction. 

Michael donors and acceptors are common components in Bronsted base-mediated catalysis. Such transformations offer an uncomplicated route towards all-carbon quaternary stereocenters. In the most basic form, a, 5-unsaturated aldehydes are highly reactive templates towards nucleophilic reactions. Under such conditions, mechanistic studies show no polymerization of the unsaturated aldehydes under cinchona alkaloid catalysis [10]. This absence of polymerization is a key mechanistic indicator that the quinucUdine nitrogen of the catalyst does not act as a nucleophilic promoter. Rather, the quinucUdine nitrogen acts, as predicted, in a Bronsted basic deprotonation-activation of various cycUc and acyclic... 

The synthetic utility of the bifunctional catalysts in various organic transformations with chiral cyclohexane-diamine derived thioureas was established through the works of Jacobsen, Takemoto, Johnston, Li, Wang, and Tsogoeva. In the last decade, asymmetric conjugate-type reactions have become popular with cinchona alkaloid derived thioureas. The next section presents non-traditional asymmetric reactions of nitroolefins, enones, imines, and cycloadditions to highlight the role of chiral Bronsted base derived thiourea catalysts. 

Apart from acting as effective Lewis base catalysts, the quinuclidine structure of cinchona alkaloids can also participate in the other cycloaddition reaction by a different catalytic mechanism. Calter et al. described an interesting asymmetric interrupted Feist-Benary reaction between ethyl bromopyruvates and cyclohexadione. They proposed that the protonated cinchona alkaloid would perform as a Bronsted acid to form hydrogen-bonding interaction with a-ketoester moiety, rendering it more electrophilic toward attack by either the enol or enolate of cydohexandione. Then intramolecular alkylation would afford the formal [3 + 2] cycloadduct (Scheme 10.12) [16]. 

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