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 s yn- and a nti-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 syn- and anti-α-alkyl-β-hydroxy esters with high diastereoselectivity.