Rhodium‐Catalyzed Homogeneous Enantioselective Transfer Hydrogenation of 1‐Naphthol Derivatives: Solvent‐Tuning of the Chemoselectivity

Abstract In the past several decades, hydrogenation of naphthol derivatives catalyzed by heterogeneous metal catalysts has been widely reported, but precise control of chemo‐, regio‐, and enantioselectivity remains an unresolved challenge. Herein we report the first homogeneous chemo and enantioselective transfer hydrogenation of 1‐naphthol derivatives catalyzed by tethered rhodium‐diamine catalysts with HCOONa reductant affording a broad range of 1‐tetralones and chiral 1,2,3,4‐tetrahydro‐1‐nanphols in high yields with excellent chemo and enantioselectivities, respectively. Preliminary mechanistic study reveals that 1‐naphthol is reduced via a sequential reaction pathway including dearomative tautomerization, 1,4‐hydride addition, and 1,2‐hydride addition in sequence. 1,1,1,3,3,3‐Hexafluoroisopropanol (HFIP) plays vital roles in controlling the reactivity and chemoselectivity of reduction of 1‐naphthols to cyclic ketones. A chemoselectivity switch could be achieved by simply changing the composition of solvent in the second‐step reduction of this one‐pot sequential reaction. This method was applied for the gram‐scale preparation of levobunolol, demonstrating the potential application of this methodology in organic synthesis.