Enantioselective synthesis of (S)- and (R)-6-hydroxy-8-nonene-carboxylates by asymmetric catalysis: a formal synthesis of (R)-α-lipoic acid and its (S)-antipode

Identification of an ε‐Keto Ester Reductase for the Efficient Synthesis of an (R)‐α‐Lipoic Acid Precursor

“…To date, a wide range of routes have been developed for the synthesis of ( R )‐LA, including resolution of racemic α‐LA or its intermediates with chemical resolving agents or lipases,6 and asymmetric syntheses using chiral auxiliaries, catalysts,7 or biocatalysts 8. However, expensive catalysts, harsh reaction conditions, low yields, and unsatisfactory optical purities make these methods impractical for industrial applications.…”

“…To date,awide range of routes have been developed for the synthesiso f( R )-LA, including resolution of racemic a-LA or its intermediates with chemical resolving agents or lipases, [6] and asymmetric syntheses using chiral auxiliaries,c atalysts, [7] or biocatalysts. [8] However, expensive catalysts,h arsh reaction conditions,l ow yields,a nd unsatisfactory optical purities make these methods impractical for industrial applications.C urrently,t he synthesis of (R)-LA on an industrial scale still depends on the chemical resolution of its racemicm ixture,w hich is produced from ethyl 8-chloro-6-oxooctanoate (ECOO)b yN aBH 4 reduction, and as ubsequent two-stage synthesis (Scheme 1, Route 1).…”

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“…This ketone allylation procedure is more reliable and experimentally simpler than the allylation of aldehydes 10. 13, 30 We are currently applying our catalyst system to other Lewis acid catalyzed processes.…”

Optimisation, Scope and Limitations of Enantioselective Aldol Reactions of an S-Ketene Silyl Acetal with Aliphatic Aldehydes under (R)-BINOL-Titanium(IV) Catalysis Conditions

“…Enzyme‐catalysed reactions of key intermediates2 have frequently been utilised, but “chemical” routes, such as the iron‐mediated method developed by Grée3 or the Sharpless asymmetric dihydroxylation reaction, have also been employed 4. We have recently successfully employed asymmetric allylation to prepare enantiopure homoallyl alcohols that can serve as useful intermediates in the synthesis of 1 5 …”