Rhodium‐catalyzed homogeneous enantioselective transfer hydrogenation of 1‐naphthol derivatives: solvent‐tuning of the chemoselective

The hydrogenation of naphthol derivatives catalyzed by heterogeneous metal catalysts has been widely reported over the past few decades, but the precise control of chemo‐, regio‐, and enantioselectivity remains an unsolved challenge. Here, we report the first homogeneous chemical and enantioselective transfer hydrogenation of 1‐naphthol derivatives catalyzed by a rhodium‐diamine catalyst and HCOONa reducing agent, providing a broad range of 1‐tetralones and chiral 1,2,3,4‐tetrahydro‐1‐naphthols with high yields and excellent chemical and enantioselectivity, respectively. Preliminary mechanistic studies showed that 1‐naphthol was reduced by a sequential reaction pathway, including dearomative tautomerization, 1,4‐hydride addition and 1,2‐hydride addition. 1,1,1,3,3,3‐Hexafluoroisopropanol (HFIP) plays a crucial role in controlling the reactivity and chemoselectivity of the reduction of 1‐naphthol to cyclic ketone. 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.