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

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.