Manganese(I)-CatalyzedEnantioselective Formal Anti-MarkovnikovHydroalkoxylation of Racemic Allylic Alcohols: A Borrowing HydrogenAccess

An enantioselective manganese(I)-catalyzed formal anti-Markovnikov hydroalkoxylation of racemic allylic alcohols has been developed using a chiral N₆-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.