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

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.