Asymmetric Synthesis of Chiral 2‑Cyclohexenones with Quaternary Stereocenters via Ene-Reductase Catalyzed Desymmetrization of 2,5-Cyclohexadienones

Stereoselective synthesis of quaternary stereocenters represents a significant challenge in organic chemistry. Herein, we describe the use of ene-reductases OPR3 and YqjM for the efficient asymmetric synthesis of chiral 4,4-disubstituted 2-cyclohexenones via desymmetrizing hydrogenation of prochiral...

Full description

Saved in:
Bibliographic Details
Published in:ACS catalysis 2024-05, Vol.14 (9), p.7256-7266
Main Authors: Friess, Michael, Sahrawat, Amit Singh, Kerschbaumer, Bianca, Wallner, Silvia, Torvisco, Ana, Fischer, Roland, Gruber, Karl, Macheroux, Peter, Breinbauer, Rolf
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Stereoselective synthesis of quaternary stereocenters represents a significant challenge in organic chemistry. Herein, we describe the use of ene-reductases OPR3 and YqjM for the efficient asymmetric synthesis of chiral 4,4-disubstituted 2-cyclohexenones via desymmetrizing hydrogenation of prochiral 4,4-disubstituted 2,5-cyclohexadienones. This transformation breaks the symmetry of the cyclohexadienone substrates, generating valuable quaternary stereocenters with high enantioselectivities (ee, up to >99%). The mechanistic causes for the observed high enantioselectivities were investigated both experimentally (stopped-flow kinetics) as well as theoretically (quantum mechanics/molecular mechanics calculations). The synthetic potential of the resulting chiral enones was demonstrated in several diversification reactions in which the stereochemical integrity of the quaternary stereocenter could be preserved.
ISSN:2155-5435
2155-5435
DOI:10.1021/acscatal.4c00276