Kinetic Resolution of Tertiary Allylic Alcohols: Highly Enantioselective Access to Cyclic Ethers Bearing an α-Tetrasubstituted Stereocenter

A chiral phosphoric acid-catalyzed kinetic resolution of tertiary allylic alcohols was developed to provide structurally valuable enantioenriched 2,2-disubstituted tetrahydrofurans, tetrahydropyrans, and oxepane. A variety of tertiary allylic alcohols were resolved with selectivity factors of <= 120. A tertiary allylic carbocationic intermediate mediates the enantioselective intramolecular substitution to achieve high regio- and enantioselectivity. A gram-scale reaction with low catalyst loading and subsequent transformations of the recovered alcohols and products demonstrated the utility of this method.

Automated summary

A novel chiral phosphoric acid-catalyzed kinetic resolution was developed for the synthesis of enantioenriched organic compounds. High efficiency and selectivity were achieved through enantioselective intramolecular substitution. The method showed success at laboratory scale and in product transformations.