Asymmetric Aldols Catalysed by Proline and its Derivatives

The direct proline-catalysed aldoi in the presence of water has been screened with water-compatible Lewis acid cocatalysts. Chlorides of zinc s group proved best, and the optimized formation of anti-products in 99% ee was obtained with L-proline/ZnCl2 in 4 1 DMSO/water. Adding cobalt(II) chloride as a co-catalyst to L-proline-promoted direct aldols substantially improves selectivity, giving yield/de/ee up to 93/96/99%. Cobalt(II) is proposed to preorganize two proUnes. (g) 

A rare chemo- and stereo-selective cross-aldol between aliphatic aldehydes, catalysed by proline and an axially chiral amino sulfonamide, links a simple aldehyde with an a-chloroaldehyde the chemoselectivity arises from the steric instability of 0 the enamine derived from the haloaldehyde. (g) 

Simple A/-proline-based dipeptides catalyse direct aldols of aldehydes with a wide range of ketones, giving yield/de/ee up to 99/ 98 (syn)/97%, at room temperature in 0 brine, with 2,4-dinitrophenol as co-catalyst. A simple organocatalyst, the methyl 0 ester of (S)-proline-(S)-phenylalanine, promotes high-yielding aldols with up to 95% ee and 82% de (anti-) under solvent-free conditions at —20 °C. Lack of solvent should 0 maximize substrate-catalyst noncovalent interactions. 0 

In model aldol reactions, yield/de/ee performance of up to 100/94/97% has (g) been achieved using prolinamide-thiourea catalysts in toluene at —20°C. Chiral prolinamide-thioureas catalyse direct aldols in high yield/de/ee.  

Prolinamides bearing 2-hydroxy-3-aminopinane units catalyse aldols of cyclic ketones with aromatic aldehydes in good yicAAldelee  

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