Control of Diastereoselectivity by Solvent Effects in the Addition of Grignard Reagents to Enantiopure t-Butylsulfinimine:  Syntheses of the Stereoisomers of the Hydroxyl Derivatives of Sibutramine

An efficient method has been developed to prepare all four isomers of the hydroxyl derivatives of sibutramine by addition of Grignard reagents (R)- or (S)-5 to a single enantiomer of sulfinyl imine (R)-1 simply by tuning the reaction solvent. The phenomenon of the reversed diastereoselectivity in CH2Cl2 and THF implied that the reaction may proceed through a chelated cyclic transition state in CH2Cl2 and nonchelated acyclic transition state in THF.