Atom transfer radical cyclization (ATRC) applied to a chemoenzymatic synthesis of Quercus lactones

The natural fragrances (+)-trans whisky lactone 2 and (+)-trans cognac lactone 4, together with a minor amount of their (−)-cis stereoisomers, were prepared in 50% and 42% overall yield, respectively, starting from racemic 1-hepten-3-ol (±)-5 and 1-octen-3-ol (±)-6. The procedure involved first the enantioconvergent, lipase mediated transformation of the secondary allylic alcohols derived dichloroacetates (±)-7 and (±)-8 into the corresponding homochiral (+)-7 and (+)-8, combined with their cyclization under a transition metal catalyzed atom transfer process.

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(3S)-1-Hepten-3-olC7H14OEe = 95%[α]D25=+10.3 (c 1.45, pentane)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(3S)-1-Octen-3-olC8H16OEe = 95%[α]D25=+7.0 (c 1.0, pentane)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(1R)-1-Butyl-2-propenyl dichloroacetateC9H14Cl2O4Ee = >99.9%[α]D25=+9.5 (c 1.35, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1R)

(1R)-1-Pentyl-2-propenyl dichloroacetateC10H16Cl2O2Ee = >99.9%[α]D25=+7.2 (c 1.2, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1R)

(1S)-1-Butyl-2-propenyl acetateC9H16O2Ee = >99.9%[α]D25=-15 (c 3.1, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(1S)-1-Pentyl-2-propenyl acetateC10H18O2Ee = >99.9%[α]D25=-11.5 (c 2.8, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)