Principles and Concept of the Aldol Reaction

The aldol reaction is a classical C-C bond formation reaction. As exemplified in Scheme 1, the first step of the aldol reaction is the enolisation of the carbonyl compound 1. This forms the enolate 2 as (E) or (Z)-enolate. For many methods, the selective formation of either (E) or (Z) enolate is required for the stereoselective outcome of the reaction (vide infra). Next, enolate 2 attacks nucleophilic the carbonyl 3 forming the aldol product 4. In the case of the cross aldol reaction both 1 and 3 are carbonyl compounds. Therefore, the reaction conditions need to be adjusted so that a differentiation of both carbonyls is possible. In most cases, enolate 2 is either preformed and carbonyl 3 has a higher electrophilicity (i.e. as an aldehyde).

Generally speaking, the aldol product 4 mimics the structural scaffold of polyketides, therefore it has been extensively used in total synthesis campaigns for polyketides.