Highly Efficient and Enantioselective Iridium-Catalyzed Asymmetric Reductive Cycloetherification

A catalytic protocol for the iridium-catalyzed asymmetric hydrogenation (AH) of γ- or δ-hydroxy ketones to rapidly assemble various aliphatic enantioenriched tetrahydrofurans (THFs) or tetrahydropyrans (THPs) is disclosed. A wide range of enantioenriched THFs or THPs were obtained in high yields and excellent enantioselectivities (up to 99% and up to 96.5:3.5 er). The dynamic kinetic resolution asymmetric hydrogenation (DKR-AH) process was also achieved, simultaneously constructing enantioenriched THP scaffolds with two contiguous stereogenic centers with high yields and stereoselectivities (up to 92% yield, up to 98.5:1.5 er and >20:1 dr). Mechanistic investigation indicates that the key step of the reaction involves the AH of the challenging cyclic, aliphatic oxocarbenium ions. Furthermore, this catalytic enantioselective approach could be carried out on a gram scale, and various enantioenriched cyclic ethers were further transformed into an array of useful building blocks for enantioenriched natural products and bioactive molecules.