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Updated: Jun 5, 2025

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
HTE-Enabled Development of an Ene-Reductase-Catalyzed Desymmetrization: Remote Control of All-Carbon Quaternary
David A Petrone1, Damien Valette2, Olivia Boyd3
1Process Research & Development, MRL, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Abstract:
We report the remote stereocontrol of all-carbon quaternary γ-centers via an ene-reductase (ERED)-catalyzed desymmetrization of prochiral cyclohexadienones. By leveraging high-throughput experimentation (HTE) protocols, we were able to rapidly identify EREDs capable of desymmetrizing both spirocyclic cyclohexadienones and non-spirocyclic 2,6-disubstituted cyclohexadienone substrates in up to 85% yield with excellent levels of stereoselectivity (up to >99% ee and >20:1 dr) under mild reaction conditions.
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