Enantioselective Hydrogenation toward Chiral 3‑Aryloxy Tetrahydrofurans Enabled by Spiro Ir-PNN Catalysts Containing an Unusual 5‑Substituted Chiral Oxazoline Unit
datasetposted on 2022-01-28, 21:44 authored by Xue-Song Gu, Ying Xiong, Fan Yang, Na Yu, Pu-Cha Yan, Jian-Hua Xie, Qi-Lin Zhou
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.
prevalent structural motifsmany approved drugsformal enantioselective synthesiscatalyzed asymmetric hydrogenation1 mol %),simple dehydration constitutespnn catalysts containingchiral spiro pnnaryloxy pyrrolidine units91 – 962 – 0spiro irligands containingdehydration steparyloxy tetrahydrofurans96 %)synthetic utilitysuccessfully implementedstraightforward approachracemic αprotocol alongmild conditionhigh yieldshigh enantioselectivitiesee ),clinical candidatesabsolutely stereospecific