A highly efficient chemoenzymatic process to produce ( <i>R</i> )-6,7-dihydroxygeraniol

The efficient asymmetric dihydroxylation of 6,7-epoxygeraniol was performed using a chemoenzymatic&#13;\nprocess employing a yeast epoxide hydrolase (EH) resolution stereoinversion step, followed by&#13;\nstereoretentive chemical hydrolysis of the remaining epoxide to produce (6 R)-6,7-dihydroxygeraniol&#13;\nat unprecedented high enantiometic excess (ee) (&gt;97.5%) and high isolated yield (72 mol % overall&#13;\nyield over 5 steps from commercially available geraniol). The enzymatic process was completed&#13;\nwithin 2 h at 250 g/L substrate loading reaching &gt; 49.5 mass % conversion of the racemic epoxide.&#13;\nThe reaction was self-limiting and furnished both the homochiral (6 R)-triol and the residual (6 R)-&#13;\nepoxide at &gt; 99% ee, due to enantio-inversion of the (6S)-epoxide. The (6 R)-epoxide was&#13;\nsubsequently chemically hydrolysed, without first needing to separate the epoxide and triol&#13;\nproducts, to afford the desired (6 R)-triol product in &gt;97.5% ee, at multigram scale. This&#13;\nchemoenzymatic procedure offers an excellent alternative to chemical asymmetric epoxidation or&#13;\ndihydroxylation for the production of enantiopure 6,7-dihydroxygeranyl and 6,7-epoxygeranyl type&#13;\ncompounds in general. It exemplifies the benefits of using greener EH bioprocesses to produce&#13;\nsuch compounds in high ee’s and high isolated yields.