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

Org Lett. 2005 Jun 23;7(13):2599-602. doi: 10.1021/ol0507017.

Abstract

[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.

MeSH terms

  • Cyclobutanes / chemical synthesis*
  • Cyclobutanes / chemistry
  • Hydroxyl Radical / chemistry
  • Indicators and Reagents
  • Molecular Structure
  • Solvents
  • Stereoisomerism
  • Sulfinic Acids / chemistry*

Substances

  • Cyclobutanes
  • Indicators and Reagents
  • Solvents
  • Sulfinic Acids
  • Hydroxyl Radical
  • sibutramine