An enantioselective manganese(I)-catalyzed formal anti-Markovnikov hydroalkoxylation of racemic allylic alcohols has been developed using a chiral N-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 and derivatization of chiral γ-alkoxypropanol to a drug molecule, ()-dapoxetine, for the treatment of premature ejaculation and erectile dysfunction. Mechanistic studies support that the reaction proceeds via a hydrogen-borrowing cascade reaction pathway.
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Manganese(I)-Catalyzed Enantioselective Formal Anti-Markovnikov Hydroalkoxylation of Racemic Allylic Alcohols: A Borrowing Hydrogen Access.
Org Lett
March 2025
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
An enantioselective manganese(I)-catalyzed formal anti-Markovnikov hydroalkoxylation of racemic allylic alcohols has been developed using a chiral N-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 and derivatization of chiral γ-alkoxypropanol to a drug molecule, ()-dapoxetine, for the treatment of premature ejaculation and erectile dysfunction. Mechanistic studies support that the reaction proceeds via a hydrogen-borrowing cascade reaction pathway.
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