Reversed Stereochemical Control in the Presence of CeCl3and TiCl4in the Lewis Acid Mediated Reduction of α-Alkyl-β-keto Esters by Metal Hydrides. A General Methodology for the Diastereoselective Synthesis ofsyn- andanti-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.