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.
[reaction: see text] 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 CH(2)Cl(2) and THF implied that the reaction may proceed through a chelated cyclic transition state in CH(2)Cl(2) and nonchelated acyclic transition state in THF.
Lu
Bruce Z
BZ
Chemical Process Research and Development, Sepracor, Inc., 84 Waterford Drive, Marlborough, Massachusetts 01752, USA. zlu@rdg.boehringer-ingelheim.com
Senanayake
Chris
C
Li
Nansheng
N
Han
Zhengxu
Z
Bakale
Roger P
RP
Wald
Stephen A
SA
D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry; D007202:Indicators and Reagents; D015394:Molecular Structure; D012997:Solvents; D013237:Stereoisomerism; D013441:Sulfinic Acids / Q000737:chemistry*
D003503:Cyclobutanes; D007202:Indicators and Reagents; D012997:Solvents; D013441:Sulfinic Acids; D017665:Hydroxyl Radical; C058254:sibutramine