Catalytic Aldol Additions

It was 1973 when Mukaiyama and coworkers described the first application of silyl enol ethers in aldol additions.¹ This reaction is promoted by Lewis acids and allowed a catalytic and an enantioselective execution for the first time.² Moreover, the regioselectivity can be controlled efficiently by using defined silyl enol ether of unsymmetrical ketones. High chemoselectivities were observed by using aldehydes, ketones and carboxylic esters in these transformations (Scheme 3.1).^3,4

The level and the sense of stereoselectivity often vary and depend on the aldehydes, silyl enol ethers and on the Lewis acids used. The stereochemical results have been rationalized by considering so-called open transitions states (Scheme 3.2).⁵ This illustration is a simple working model based on repulsive forces only. The influence of different Lewis acids, the influence of different substituents and the fate of silyl group during the reaction were not involved in this model. For further discussion and mechanistic understanding see Hiraiwa et al. and others.⁶