Asymmetric Enamide–Imine Tautomerism in the Kinetic Resolution of Tertiary Alcohols

Abstract

AbstractAn efficient protocol for kinetic resolution of tertiary alcohols has been developed through an unprecedented asymmetric enamide‐imine tautomerism process enabled by chiral phosphoric acid catalysis. A broad range of racemic 2‐arylsulfonamido tertiary allyl alcohols could be kinetically resolved with excellent kinetic resolution performances (with s‐factor up to >200). This method is particularly effective for a series of 1,1‐dialkyl substituted allyl alcohols, which produced chiral tertiary alcohols that would be difficult to access via other asymmetric methods. Facile and versatile transformations of the chiral α‐hydroxy imine and enamide products, especially the efficient stereodivergent synthesis of all four stereoisomers of β‐amino tertiary alcohols using one enantiomer of the catalyst, demonstrated the value of this kinetic resolution method.