Stereoselective reduction of enantiopure α-l-amino-β-keto esters using oxazaborolidine catalysts for the synthesis of statine analogues

An efficient diastereoselective synthesis of Boc-protected 4-amino 3-hydroxy esters starting from natural amino acids is described.The key synthetic strategy involves diastereoselective reduction of -L-amino--keto esters in the presence of enantiopure R and S-2-Methyl-CBS-oxazaborolidine catalysts using borane as hydride source.The product diastereoselectivity depends upon the use of (R) or (S) enantiomer of 2-Methyl-CBS-oxazaborolidine.A reasonable mechanism is included which explains the diastereoselectivity of the reactions with the use of different enantiomers of 2-Methyl-CBS-oxazaborolidine.Furthermore, the resulting diastereomeric mixture of the reduced products can be separated by column chromatography to gain access to the single pure diastereomers.