HTE-Enabled Development of an Ene-Reductase-Catalyzed Desymmetrization: Remote Control of All-Carbon Quaternary γ-Centers
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.
Authors
- Damien Valette (ORCID: https://orcid.org/0000-0002-1620-3502)
- Erin Plasek (ORCID: https://orcid.org/0000-0002-7236-4853)
- Feng Peng (ORCID: https://orcid.org/0000-0002-2382-2862)
- Justin A. Newman (ORCID: https://orcid.org/0000-0002-2498-1259)
- Olivia Boyd
- Matthew L. Maddess (ORCID: https://orcid.org/0000-0002-7273-528X)
- Xiao Wang (ORCID: https://orcid.org/0000-0003-3238-5366)
- Tetsuji Itoh (ORCID: https://orcid.org/0000-0001-8012-7965)
- David A. Petrone
- Guangxin Shao
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Department for International Development (GB)
- Process Research Ortech (Canada) (CA)
- KPMG (United Kingdom) (GB)
Publication Details
- Journal
- Organic Letters
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1021/acs.orglett.4c04383
- Citations
- 4
- Primary Topic
- Asymmetric Hydrogenation and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 0.63