Rh/Hf Cocatalyzed Asymmetric Hydrogenation of 3-Ylidenephthalides with Water

Chiral 3-substituted phthalides are widely present in numerous natural products and display a variety of bioactivities. The asymmetric reduction of 3-ylidenephthalides compounds with water as hydrogen source was developed by a Rh/Hf cocatalytic system, allowing the straightforward preparation of chiral 3-substituted phthalides in good yield with high optical purities. The practical utility of this protocol is demonstrated through gram-scale synthesis and downstream transformation to chiral 1,2-phenylenedimethanols. Moreover, a range of optically enriched chiral deuterated phthalides were synthesized by using D₂O as a cost-effective deuterium source.