Highly stereoselective TiCl4-mediated aldol reactions from (S)-2-benzyloxy-3-pentanone

Stereoselectivity of TiCl4-mediated aldol reactions from (S)-2-benzyloxy-3-pentanone is dramatically improved when the reaction is carried out in the presence of 1.1 equiv of tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME). The resultant 2,4-syn-4,5-syn adducts are then obtained in diastereomeric ratios up to 97:3, which proves that the appropriate choice of the Lewis acid (TiCl4-THF or DME vs Ti(i-PrO)Cl-3) engaged in the process permits access to both syn-aldol adducts.