Asymmetric Aldols Catalysed by Other Organocatalysts

Co-catalysis by commercially available chiral frani-l,2-diaminocyclohexane and hex-anedioic acid gives excellent results for aldols in aqueous methanol cyclic ketones give yields up to 78%, 20 1 anti syn-selec ivity, and 94% ee, whereas hydroxyace-tone gives comparable results but with iyn-diastereoselectivity.  

Direct aldols of ketones and glyoxylates (RC0C02Me) give high ee using axially chiral diimine catalysts (55) in acetic acid media, but MS and other evidence suggests that the related imine-primary amine (56) - formed by acid-catalysed equilibration - is the immediate catalytic species. ° 

Dibenz[c,e]azepine salt (57) - derived fromfranj-l,2-diaminocyclohexane -promotes highly diastereo- and enantio-selective crossed-aldols of cyclohexanone and aromatic aldehydes. Chiral l-amino-2-sulfonamidocyclohexanes catalyse syn-aldols of benzaldehydes and hydroxyacetone. A chiral l°-3° diamine promotes 0 aldol reactions of acetone and -unsaturated a-ketoesters in yields up to 99% and (g) ees up to 96%.  

Enantiopure tridentate ligands bearing hydroxyl, sulflnyl, and amino groups give yield/ee up to 98/97% in direct aldols.  

The diastereoselectivities observed in aldol reactions of cyclic ketones catalysed by di- and tri-amino-organocatalysts is strongly influenced by the nature, size, and hydrogen-bond-donor ability of the Brpnsted acid additives employed.  

The simple trans-diamine (67) gives excellent enantio- and diastereo-selectivities in a variety of aldol reactions in ethanol de is up to 98% anti, but it switches over to comparable syn-selectivity just by changing the solvent to water.  

Substituent effects have been compared in 4-substituted benzaldehydes versus 4-substituted (phenylethynyl)benzaldehydes, 4-X-C6H4-C=C-4-QH4-CHO. For example, changing a cyano substituent to methoxy in the former causes a 54-fold decrease in the rate of an aldol reaction, whereas the factor was only 1.4 in the latter series. 

Pyruvic aldehyde dimethyl acetal, MeCO-CH(OMe)2, undergoes enantioselective direct aldol reaction with isatin derivatives, using a bifimctional organocatalytic combination of a cinchona-derived primary amine and trichloroacetic acid. Glycosyl-a-aminotetrazoles efficiently catalyse enantioselective aldol reactions DPT calculations have been used to identify the origin of the selectivity.  

New chiral spiro[4,4]-diphosphine oxides catalyse double-aldols of ketones with two molecules of aldehyde in good yield, de and ee  

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