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

摘要

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 beta,beta-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.