Asymmetric organocatalysts prolinamides

Importantly, prolinamide catalysts (Figure 6.3) work well in Michael addition reactions using nitro-olefins as acceptors. iV-Tritylprolinamide 33 and aminonaphthyridine-derived ProNap 34 served as organocatalysts in asymmetric Michael additions of aldehydes and cyclohexanone to nitro-alkenes. Proline-functionalised C3-symmetric 1,3,5-triallq lbenzene 35 was screened in the reaction of cyclohexanone to nitrostyrene to afford the Michael adducts in good yields and diastereoselectivity but low enantioselectivity. 

Sugar-hased prolinamide 16m has also been employed as catalyst for the asymmetric Michael addition of cyclohexanones to p-nitroslyrenes. During optimisation of the reaction conditions, the authors found that the polarity of the solvent does not modify the yield or stereoselectivity, but the best ee was obtained under neat conditions at -20 °C. Ammonium ionic liquids 41a,b are also efficient organocatalysts for the asymmetric Michael addition of aldehydes to nitro-olefins giving the adducts with excellent yields and enantioselectivities and modest to high diastereoselectivities. 

A series of 4-hydroxyprolinamides, 4-acylo>q prolinamides, 4-silylo)yprolin-amides and 4-sulfonylo>qq3rolinamides have been synthesised and studied as useful organocatalysts for asymmetric transformations of organic compounds (Figure 10.4). 

The silyl ether of a elosely related 4-hydroxy-prolinamide alcohol was also successfully applied as an organocatalyst to the asymmetric aldolisation of either cyclic or acyclic ketones with a range of aromatic aldehydes in water. This catalyst was highly efficient and as low as 1 mol % of catalyst loading allowed high yields and excellent diastereo- and enantioselectivities to be obtained, as shown in Scheme 2.14. 

In a similar area, Ludtke et al. have employed a robust cysteine-derived prolinamide as an organocatalyst to promote the asymmetric aldolisation of... 

However, in contrast to the relatively well-developed cyanation of aldimines, limited reports were related to the cyanation of ketoimines. In this context, Feng et al. have designed a novel Ai, A -dioxide catalyst derived from BINOL and prolinamide in order to be applied as organocatalyst for the asymmetric Strecker reaction of ketoimines with fairly wide substrate scope and excellent enantioselectivities of up to 99% ee (Scheme 3.34)." A low catalyst loading of 2 mol % combined with mild reaction conditions and an operational simplicity made this strategy facile to be used for the synthesis of pharmaceutically important chiral disubstituted a-amino nitriles. 

Monge-Marcet, A., Cattoen, X., Alonso, D.A., Najera, C, Man, M.W.C., and Pleixats, R. (2012) Recyclable silica-supported prolinamide organocatalysts for direct asymmetric aldol reaction in water. Green Chem, 14 (6), 1601-1610. 

In addition to organometaUic dendrimers for asymmetric catalysis, a number of dendritic organocatalysts have been developed and successfully applied in different asymmetric reactions in the absence of any metal [63]. In 2009, Parquette and coworkers [64] reported a new kind of folded pyridine-2,6-dicarboxamide dendrons (36) for direct aldol reaction. These dendritic prolinamide catalysts were tested for the aldol reactions of various acycUc and cydic ketones with 4-nitrobenzaldehyde (Figure 4.33). Remarkable dendritic effects on both the enantioselectivity and... 

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