Asymmetric Mukaiyama Aldol Reaction Catalyzed by Hydrogen Bonding

Significance

An organocatalytic asymmetric Mukaiyama aldol reaction has been developed. Addition of O-silyl-N,O-ketene acetal 1 to aldehydes 2 in the presence of 10 mol% of chiral TADDOL 3 gives β-hydroxy amides 4 in high yields, enantio­selectivities, and diastereoselectivities. A few examples of products 4 have been transformed into the corresponding β-hydroxy aldehydes in good yields and with preservation of the stereochemistry. Furthermore, the first crystal structure of the complex between a TADDOL and an aldehyde illustrating the coordination of the carbonyl group by a single hydrogen bonding is provided.