Asymmetric Aldol Reactions Using (S,S)-(+)-Pseudoephedrine-Based Amides: Stereoselective Synthesis of α-Methyl-β-hydroxy Acids, Esters, Ketones, and 1,3-Syn and 1,3-Anti Diols

Abstract
A very efficient method for performing stereoselective aldol reactions is reported. The reaction of (S, S)-(+)-pseudoephedrine-derived propionamide enolates with several aldehydes yielded exclusively one of the four possible diastereomers in good yields, although transmetalation of the firstly generated 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-formed syn-alpha-methyl-beta-hydroxy amides were transformed into other valuable chiral nonracemic synthons such as alpha-methyl-beta-hydroxyacids, esters, and ketones. Finally, a stereocontrolled reduction procedure starting from the so-obtained alpha-methyl-beta-hydroxy ketones has been developed allowing 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.

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