Catalytic Contra-Thermodynamic Isomerization–Asymmetric Hydroboration of Alkenyl Alcohols and Amines

Catalytic isomerization of alkenes is a powerful tool for the construction of complex synthetically valuable molecules due to their redox-neutral, atom- and step-economical nature. However, traditional catalytic asymmetric isomerization of alkenes typically required the use of a heteroatomic group such as OH or NR2 as the thermodynamic driving force (i.e., the C═C double bond isomerizes along the direction of heteroatomic groups). Here, we present a contra-thermodynamic isomerization/asymmetric hydroboration of alkenyl alcohols and amines, in which the C═C double bond isomerizes along the opposite direction of OR and NR2. Compared to the traditional thermal isomerizations, this reaction overcomes the unfavorable thermodynamic bias to form a contra-thermodynamic alkene intermediate, followed by an irreversible asymmetric terminal hydroboration to provide highly synthetically valuable chiral 1,n-boryl ethers and amines. This protocol shows a wide substrate scope, including allylic alcohols, homoallylic alcohols, alkenyl alcohols, protected alkenyl alcohols, and various free and protected alkenyl amines. The synthetic utilities and practicability of this method were demonstrated by gram-scale reactions, diverse product transformations, and its applications in the synthesis of bioactive molecules. Preliminary mechanistic studies show that this reaction involves dissociative alkene isomerization and an asymmetric hydroboration of 1,1-disubstituted alkene intermediates.