Organocatalytic Michael addition
Propanal and (E)-β-nitrostyrene react in the presence of the trimethylsilyl ether of (S)-diphenylprolinol (Hayashi, 2005). The catalyst forms an E enamine with the aldehyde, and the bulky CPh2OTMS group blocks one of its faces, so that the nitroalkene can approach only from the other.
Two adjacent stereocentres are formed in a single step: the syn adduct, (2R,3S)-2-methyl-4-nitro-3-phenylbutanal, in 99% ee. The nitro group can later be reduced to an amine, and the product is a precursor of γ-amino acids and pyrrolidines; with this reaction as the key step, Hayashi prepared the antiviral oseltamivir in three one-pot operations.