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 α-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.