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Alcohol Dehydrogenases and N‐Heterocyclic Carbene Gold(I) Catalysts: Design of a Chemoenzymatic Cascade towards Optically Active β,β‐Disubstituted Allylic Alcohols
Author(s) -
GonzálezGranda Sergio,
Lavandera Iván,
GotorFernández Vicente
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202015215
Subject(s) - allylic rearrangement , chemistry , carbene , ketone , stereoselectivity , catalysis , alcohol dehydrogenase , alcohol , kinetic resolution , enantiomeric excess , enantiomer , selectivity , combinatorial chemistry , medicinal chemistry , organic chemistry , enantioselective synthesis , stereochemistry
Abstract 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) (IPrAuNTf 2 ) 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.