Alcohol Dehydrogenases and N‐Heterocyclic Carbene Gold(I) Catalysts: Design of a Chemoenzymatic Cascade towards Optically Active β,β‐Disubstituted Allylic Alcohols

The combination of gold(I) and enzyme catalysis is used in a two‐step approach, including Meyer–Schuster rearrangement of a series of readily available propargylic alcohols followed by stereoselective bioreduction of the corresponding allylic ketone intermediates, to provide optically pure β,β‐disubstituted allylic alcohols. This cascade involves a gold N‐heterocyclic carbene and an enzyme, demonstrating the compatibility of both catalyst types in aqueous medium under mild reaction conditions. The combination of [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene][bis(trifluoromethanesulfonyl)‐imide]gold(I) (IPrAuNTf2) and a selective alcohol dehydrogenase (ADH‐A from Rhodococcus ruber, KRED‐P1‐A12 or KRED‐P3‐G09) led to the synthesis of a series of optically active (E)‐4‐arylpent‐3‐en‐2‐ols in good yields (65–86 %). The approach was also extended to various 2‐hetarylpent‐3‐yn‐2‐ol, hexynol, and butynol derivatives. The use of alcohol dehydrogenases of opposite selectivity led to the production of both allyl alcohol enantiomers (93‐>99 % ee) for a broad panel of substrates. A concurrent process involving a gold N‐heterocyclic carbene (IPrAuNTf2) and an alcohol dehydrogenase is described for the first time. This cascade approach allows the development of a Meyer–Schuster rearrangement for the transformation of racemic propargylic alcohols, mostly with good selectivities towards the corresponding E‐allylic ketone intermediates, in aqueous medium, which are subsequently reduced to obtain the desired alcohol enantiomers with excellent optical purities.