Catalysis with Natural Cinchona Alkaloids

In recent years, various studies were reported on the asymmetric conjugate addition of nucleophiles to unsaturated compounds as catalyzed by natural cinchona alkaloids [3], For example, conjugate addition of 1,3-dicarbonyl compounds 

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The adducts were isolated in good yield and up to 75% ee. Experimental findings and DFT calculations were both consistent with noncovalent catalysis, highlighting the ability of diatyl prolinols to behave in a similar mode of action as previously attested by die pivotal work of Wynberg and coworkers in natural Cinchona alkaloid-catalysed Michael addition reactions. ... 

Most reports on organocatalytic sulfa-Michael reactions are based on Br0nsted base catalysis, in order to activate pro-nucleophiles containing a S H or a Se—H bond. The early works, appeared in the lates 1970s, featured natural cinchona alkaloids 1-4 as basic catalysts (Figure 14.1). In their seminal works, Wynberg and co-workers employed less than 1 mol% of quinine 1 as chiral catalyst for the conjugated addition of arenethiols to 2-cyclohexen-l-ones. The enantiocontrol was unsatisfactory with benzyhnercaptan [6]. The quasi-enantiomeric catalyst quinidine 2 furnished the... 

The concept of bifunctional catalysis as advanced for the natural cinchona alkaloids and cuprei(di)nes has resulted in the design and synthesis of a range of new cinchona derivatives. The major part of these novel organocatalysts are urea and thiourea cinchona derivatives together with cinchona alkaloids modified with, for example, a sulfonamide, squaramide, or guanidine group (Figure 6.8). 

Different groups reported in 2007 on the use of C9 amino cinchona alkaloids as catalysts for the stereoselective functionaUzation of branched carbonyl compounds. Connon and coworkers demonstrated that the C9 amino derivative of epidihydro-quinine (40) and epidihydroquinidine (41) were effective catalysts for the conjugate addition of aldehydes and (cyclic) ketones to nitroalkenes via enamine catalysis [99] (Scheme 6.46). The catalysts with the same configuration at C9 as in the natural cinchona alkaloid gave poor results, in line with the results obtained for... 

Catalysis with C9 Ethers of Natural Cinchona Alkaloids... 

One of the simplest approaches to the creation of an enantioselective catalyst is the adsorption of a chiral molecule (often referred to as a modifier) onto the surface of a metal catalyst. The metals most commonly employed for this type of catalysis have been the Pt group metals and Ni [29]. The most successful chiral modifiers have been naturally occurring alkaloids (Pt) and tartaric acid (Ni) (Scheme 5.2). Each system has primarily been used for hydrogenation reactions with Pt/cinchona producing ee values of greater than 90% for the hydrogenation of a-ketoesters [42, 43] ... 

Asymmetric phase-transfer catalysis is a method that has for almost three decades proven its high utility. Although its typical application is for (non-natural) amino acid synthesis, over the years other types of applications have been reported. The unique capability of quaternary ammonium salts to form chiral ion pairs with anionic intermediates gives access to stereoselective transformations that are otherwise very difficult to conduct using metal catalysts or other organocatalysts. Thus, this catalytic principle has created its own very powerful niche within the field of asymmetric catalysis. As can be seen in Table 5 below, the privileged catalyst structures are mostly Cinchona alkaloid-based, whereas the highly potent Maruoka-type catalysts have so far not been applied routinely to complex natural product total synthesis. 

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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