Synthesis of enantiopure (R)-(−)-massoialactone through ruthenium-SYNPHOS® asymmetric hydrogenation

Total synthesis of enantiopure (R)-(−)-massoialactone was achieved. The key step includes the asymmetric hydrogenation of an achiral β-keto ester using a ruthenium-SYNPHOS® catalyst to set the hydroxyl function in a stereocontrolled manner with excellent enantioselectivity (>99% ee). Ring closing metathesis (RCM) in the presence of Grubbs’ catalyst allows the final construction of the six-membered lactone.

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Methyl (R)-(−)-3-hydroxyoctanoateC9H18O3[α]D25=-26 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

Methyl (R)-(−)-3-(tert-butyl-dimethyl-silyloxy)octanoateC15H32O3Si[α]D21=-21.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(−)-3-(tert-Butyl-dimethyl-silyloxy)octanalC14H30O2Si[α]D21=-5.5 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-4-(tert-Butyl-dimethyl-silyloxy)-Non-1-yneC15H30OSi[α]D25=-17.8 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(+)-Non-1-yn-4-olC9H16O[α]D25=+23.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(+)-Non-1-en-4-olC9H18O[α]D25=+5.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Non-1-en-4-yl acrylateC12H20O2[α]D25=+9.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(−)-6-Pentyl-5,6-dihydro-2H-pyran-2-oneC11H18O[α]D25=-110.7 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)