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

Abstract

AbstractThe 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.