Manganese(I)-Catalyzed Enantioselective Formal Anti-Markovnikov Hydroalkoxylation of Racemic Allylic Alcohols: A Borrowing Hydrogen Access
Shuai-Hu Liu, Faju Li, Yan-Mei He, Qing‐Hua Fan
Abstract
An enantioselective manganese(I)-catalyzed formal anti-Markovnikov hydroalkoxylation of racemic allylic alcohols has been developed using a chiral N 6 -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 3n and derivatization of chiral γ-alkoxypropanol 3a to a drug molecule, ( S )-dapoxetine, for the treatment of premature ejaculation and erectile dysfunction. Mechanistic studies support that the reaction proceeds via a hydrogen-borrowing cascade reaction pathway.
Topics & Concepts
Markovnikov's ruleChemistryAllylic rearrangementEnantioselective synthesisCatalysisManganeseHydrogenCombinatorial chemistryOrganic chemistryMedicinal chemistryRegioselectivityAsymmetric Hydrogenation and CatalysisChemical Synthesis and AnalysisSurface Chemistry and Catalysis