Stereoselective Construction of Entire Diastereomeric Stereotetrads Based on an Asymmetric Morita–Baylis–Hillman Reaction

Abstract

A method for the enantio‐ and diastereoselective construction of all possible stereoisomers of a polypropionate stereotetrad having four contiguous stereogenic centers has been developed. The approach features an iterative sequence of cinchona‐alkaloid‐catalyzed Morita–Baylis–Hillman reaction and subsequent diastereoselective hydrogenation. By this method, benzaldehyde was successfully converted into eight diastereoisomeric 3,5‐dihydroxy‐2,4‐dimethyl‐5‐phenylpentanoic acid ester derivatives with high enantiomeric purities (99 % ee) in 25–67 % overall yield (eight steps) in a reagent‐controlled manner.