l-Tryptophan-Catalyzed Aldol Reaction in Water

Significance

Various cyclic ketones 2 and aromatic aldehydes 3 undergo direct aldol reactions in water in the presence of l-tryptophan (1) as catalyst. When cyclohexanone (2, n = 1) was used, high anti/syn rates and enantioselectivities (78-92%) could be achieved, albeit with moderate yields (42-91%). The use of ketones with other ring sizes was possible. It was found that the reactivity was lower and the enantioselectivity never exceeded 83% (for 5) when other non-cyclic amino acids were used. Protection of the acid as an ester only gave the racemic product in slightly lower yield with an anti/syn ratio of 1.3:1, showing that the acid moiety is essential for both reactivity and stereoselectivity. This is also explained by a plausible transition state.