Application of the Chiral Acyl Anion Equivalent, trans-1,3-Dithiane 1,3-Dioxide, to an Asymmetric Synthesis of (R)-Salbutamol

An enantioselective synthesis of (R)-salbutamol has been carried out using the chiral, C2 symmetric acyl anion equivalent, (1R,3R)-1,3-dithiane 1,3-dioxide, which undergoes addition to an aromatic aldehyde with very high stereocontrol at 0 degrees C. Pummerer reaction and work-up with lithium ethanethiolate generated the alpha-hydroxy thiolester in high yield and further transformations led to the target compound with high enantiomeric excess.