Asymmetric aldol reactions using (S,S)-(+)-pseudoephedrine-based amides: Stereoselective synthesis of alpha-methyl-beta-hydroxy acids, esters, ketones, and 1,3-syn and 1,3-Anti diols

A very efficient method for performing stereoselective aldol reactions is r eported. The reaction of (S,S)-(+)-pseudoephedrine-derived propionamide eno lates with several aldehydes yielded exclusively one of the four possible d iastereomers in good yields, although transmetalation of the firstly genera ted lithium enolate with a zirconium(II) salt, prior to the addition of the aldehyde, is necessary in order to achieve high syn selectivity. The so-fo rmed syn-alpha-methyl-beta-hydroxy amides were transformed into other valua ble chiral nonracemic synthons such as alpha-methyl-beta-hydroxyacids, este rs, and ketones. Finally, a stereocontrolled reduction procedure starting f rom the so-obtained alpha-methyl-beta-hydroxy ketones has been developed al lowing the synthesis of either 1,3-syn- or 1,3-anti-alpha-methyl-1,3-diols in almost enantiopure form by choosing the appropriate reaction conditions.