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

• Published in: Angewandte Chemie Vol. 133; no. 39; pp. 21504 - 21509
• Main Authors: Tang, Mengyao, Gu, Huanchao, He, Shunlong, Rajkumar, Subramani, Yang, Xiaoyu
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 20.09.2021
• Subjects: Alcohol; Alcohols; Allyl alcohol; asymmetric catalysis; Asymmetry; Catalysis; Catalysts; Chemistry; chiral Brønsted acids; enamide–imine tautomerism; Enantiomers; kinetic resolution; Phosphoric acid; Stereoisomerism; Stereoisomers; Tautomerism; tertiary alcohols
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202106151

An 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. An unprecedented kinetic resolution of 2‐amido tertiary allyl alcohols through chiral phosphoric acid‐catalyzed enamide–imine tautomerism is reported. Both dialkyl‐ and aryl‐alkyl‐disubstituted allyl alcohols were compatible with this protocol, generating α‐hydroxy imines and enamides with high enantioselectivities.