Chemo‐Enzymatic Oxidative Rearrangement of Tertiary Allylic Alcohols: Synthetic Application and Integration into a Cascade Process

A chemo‐enzymatic catalytic system, comprised of Bobbitt's salt and laccase from Trametes versicolor, allowed the [1,3]‐oxidative rearrangement of endocyclic allylic tertiary alcohols into the corresponding enones under an Oxygen atmosphere in aqueous media. The yields were in most cases quantitative, especially for the cyclopent‐2‐en‐1‐ol or the cyclohex‐2‐en‐1‐ol substrates without an electron withdrawing group (EWG) on the side chain. Transpositions of macrocyclic alkenols or tertiary alcohols bearing an EWG on the side chain were instead carried out in acetonitrile by using an immobilized laccase preparation. Dehydro‐Jasmone®, dehydro‐Hedione®, dehydro‐Muscone and other fragrance precursors were directly prepared with this procedure, while a synthetic route was developed to easily transform a cyclopentenone derivative into trans‐Magnolione® and dehydro‐Magnolione®. The rearrangement of exocyclic allylic alcohols was tested as well, and a dynamic kinetic resolution was observed: α,β‐unsaturated ketones with (E)‐configuration and a high diastereomeric excess were synthesized. Finally, the 2,2,6,6‐tetramethyl‐1‐piperidinium tetrafluoroborate (TEMPO+BF4−)/laccase catalysed oxidative rearrangement was combined with the ene‐reductase/alcohol dehydrogenase cascade process in a one‐pot three‐step synthesis of cis or trans 3‐methylcyclohexan‐1‐ol, in both cases with a high optical purity.