Prolinamides as Asymmetric Organocatalysts

Departamento de Quimica Organica and Instituto CINQUIMA, Facultad de Ciencias, Universidad de Valladolid. Paseo de Helen 7, 47011-Valladolid, Spain Email pedrosa qo.uva.es 

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

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 the area of the asymmetric organocatalytic Strecker reaction, a novel A,A -dioxide catalyst derived from BINOL and prolinamide was successfully applied at only 2 mol% of catalyst loading as an organocatalyst to the Strecker reaction of ketoimines with a fairly wide substrate scope, providing excellent enantioselectivities of up to 99% ee. In addition, a chiral thiourea catalyst was... 

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. 

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