Catalytic Asymmetric Glyoxylate–Ene Reaction: A Practical Access to α-Hydroxy Esters in High Enantiomeric Purities

An efficient asymmetric catalysis is developed for the glyoxylate–ene reaction to afford the α-hydroxy esters of biological and synthetic importance. The key to the success is the use of the chiral titanium complex prepared in situ from (i-PrO)₂TiX₂ (X = Cl or Br) and the (R)- or (S)-binaphthol in the presence of molecular sieves (MS 4A). The presence of the molecular sieves (zeolite) is clarified to facilitate the alkoxy-ligand exchange reaction. Thus, the use of MS is shown to be essential for the in situ preparation step of the chiral catalyst and not for the ene reaction step. The present catalytic process is applicable to various 1, 1-disubstituted olefins by the judicious choice of the dichloro or dibromo catalyst.