Novel cinchona alkaloid organocatalysts synthesis

Scheme 12.9 Synthesis of novel cinchona alkaloid organocatalysts with modified quinoline moiety. Reagents and conditions (a) Dt-BuAD, CH2CI2, rt, 2 h, 93% (b) PhNTf2, DMAP, CH2CI2 (c) 1. Pd(OAc)2, BINAP, Cs2C03, THF, Ph2C=NH, 2. citric acid, THF, H20 (d) 3,5-(CF3)2PhNCS, THF.

On the other hand, several cinchona alkaloid-derived primary amines have been successfully investigated as organocatalysts for asymmetric Michael additions of ketones to Michael acceptors. As an example, Lu et al. have described the first Michael addition of cyclic ketones to vinyl sulfone catalysed by a catalyst of this type, providing an easy access to chiral a-alkylated carbonyl compounds with high yields and enantioselectivities of up to 96% ee, albeit with moderate diastereoselectivities (<72% de), as shown in Scheme 1.21. This novel methodology was apphed to the synthesis of sodium cyclamate, an important compound in the artificial sweeteners industry. 

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). 

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