Manganese(I)-Catalyzed Enantioselective Formal Anti-Markovnikov Hydroalkoxylation of Racemic Allylic Alcohols: A Borrowing Hydrogen Access
An enantioselective manganese(I)-catalyzed formal anti-Markovnikov hydroalkoxylation of racemic allylic alcohols has been developed using a chiral N<sub>6</sub>-type macrocyclic ligand, affording a wide range of chiral γ-alkoxypropyl alcohols in high isolated yields with excellent enantioselectivities. The synthetic utility of this protocol was further proven by gram-scale synthesis of chiral γ-alkoxypropanol <b>3n</b> and derivatization of chiral γ-alkoxypropanol <b>3a</b> to a drug molecule, (<i>S</i>)-dapoxetine, for the treatment of premature ejaculation and erectile dysfunction. Mechanistic studies support that the reaction proceeds via a hydrogen-borrowing cascade reaction pathway.
Authors
- Faju Li
- Yan-Mei He
- Qing‐Hua Fan (ORCID: https://orcid.org/0000-0001-9675-2239)
- Shuang Liu (ORCID: https://orcid.org/0009-0001-4284-7897)
Institutions
- Chinese Academy of Sciences (CN)
- Beijing National Laboratory for Molecular Sciences (CN)
- Institute of Forensic Science (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-02-20
- DOI
- https://doi.org/10.1021/acs.orglett.5c00161
- Citations
- 6
- Primary Topic
- Asymmetric Hydrogenation and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China