Reversed stereochemical control in the presence of CeCl₃ and TiCl₄ in the Lewis acid mediated reduction of α-alkyl-β-keto esters by metal hydrides. A general methodology for the diastereoselective synthesis of syn- and anti-α-alkyl-β-hydroxy esters

The Lewis acid-mediated reduction of α-alkyl-β-keto esters has been shown to proceed by different stereochemical control depending on the nature of the metal atom. Strongly chelating TiCl₄ led to the syn isomer in high diastereomeric excess in noncoordinating solvents (CH₂Cl₂) at -78 °C with BH₃·py as reducing agent, while nonchelating CeCl₃ gave a high excess of the anti isomer in coordinating solvents (THF) at the same temperature with lithium triethylborohydride (LiEt₃BH) as reducing agent. The methodology has been successfully utilized for obtaining important synand anti-α-alkyl-β- hydroxy esters with high diastereoselectivity.