Enantioselective Hydrogenation toward Chiral 3-Aryloxy Tetrahydrofurans Enabled by Spiro Ir-PNN Catalysts Containing an Unusual 5-Substituted Chiral Oxazoline Unit

An iridium-catalyzed asymmetric hydrogenation of racemic alpha-aryloxy lactones involving dynamic kinetic resolution was successfully implemented by chiral spiro PNN-ligands containing a C5-substituted chiral oxazoline unit. This protocol along with simple dehydration constitutes the most straightforward approach to prepare enantiomerically enriched 3-aryloxy tetrahydrofurans, which are prevalent structural motifs in many approved drugs and clinical candidates. The hydrogenation step features high yields (90-96%), low catalyst loading (0.2-0.1 mol %), and high enantioselectivities (91-96% ee), and the dehydration step is absolutely stereospecific with high yields (up to 96%) under the mild condition. Moreover, the synthetic utility was further proved by the formal enantioselective synthesis of empagliflozin and production of 3-aryloxy pyrrolidine units.