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.
Subject(s)
Cyclobutanes/chemical synthesis , Sulfinic Acids/chemistry , Cyclobutanes/chemistry , Hydroxyl Radical/chemistry , Indicators and Reagents , Molecular Structure , Solvents , StereoisomerismABSTRACT
[reaction: see text] A general process for the efficient synthesis of sulfinyl transfer agents has been developed using cinchona alkaloids quinine and quinidine as chiral auxiliaries. The importance of these new and unique sulfinyl transfer agents is exemplified by the expedient synthesis of several sulfoxides in excellent enantiopurities and high yields.
Subject(s)
Cinchona Alkaloids/chemistry , Sulfinic Acids/chemical synthesis , Sulfoxides/chemical synthesis , Chemistry, Organic/methods , Molecular Structure , Quinidine/chemistry , Quinine/chemistry , Stereoisomerism , Sulfinic Acids/analysis , Sulfoxides/analysisABSTRACT
A highly diastereoselective addition of i-BuLi to a triethylmethylsulfinamide derived aldimine was used as the key step in the first asymmetric synthesis of (R)-didesmethylsibutramine, a metabolite of sibutramine for the potential treatment of CNS disorders. [reaction: see text]