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.

Chiral Ytterbium Complex‐Catalyzed Direct Asymmetric Aldol‐Tishchenko Reaction: Synthesis of anti‐1,3‐Diols

“…We expected the same configuration of the asymmetric carbon atoms, that is, (1 S ,2 S ,3 R ) (Figure 2) as observed for compounds 3 i and 3 k . Analysis of the literature data [(1 R ,3 S )‐enantiomer: [ α ] D =−7.6, 99 % ee ]24 suggested, however, formation of the same isomer (1 R ,3 S ) of compound 3 a ([ α ] D =−36, 75 % ee ). Such a reverse sense of asymmetric induction was highly improbable, but not impossible in the light of the different nature of aliphatic and aromatic ketones.…”

Synthesis of Valuable Chiral Intermediates by Isolated Ketoreductases: Application in the Synthesis of α‐Alkyl‐β‐hydroxy Ketones and 1,3‐Diols

“…They include asymmetric reductions using chiral ruthenium Ru(II) [3] or rhodium [4] catalysts or hydroboration using chiral Co(II) catalysts. [4] Methods requiring chiral starting precursors such as amides [5] and ketones, [6] or aldol condensations starting from achiral ketones, [7] through boron enolates in the presence of tertiary amines, [8] or through zirconium enolates [9] and bases like LDA, LTMP and LHMDS [10] have also been used. Compounds with high optical purities have been obtained; however, these methods are frequently not generally applicable for the synthesis of other structurally related compounds or different diastereomers of the same compounds.…”

A New Fatty Acid from the Endolichenic Fungus Massarina sp.

“…The IR absorptions at 3387 cm -1 and 1711 cm -1 indicated the presence of hydroxy and carbonyl groups, respectively. Detailed analysis of 1 H, 13 C NMR, and HSQC spectra of 1 revealed the presence of two methyls (G C 4.0 and 21.3), nine methylenes (G C 24.7-35.3), three methines (G C 41.9, 72.9, and 77.1) including two oxygenated carbons, and one carboxyl group (G C 178.8) (Table 1). These data accounted for all 1 H and 13 C NMR resonances and suggested a long-chain fatty acid.…”