Reversal of Enantioselectivity for the Desymmetrization of -1,2-Diols Catalyzed by Pyridine--oxides.

The desymmetrization of --diols with a reversal of enantioselectivity catalyzed by chiral pyridine--oxides with l-proline as a single source of chirality is reported. With chiral 3-substituted ArPNO and 2-substituted 4-(dimethylamino)pyridine--oxide as catalysts, a wide range of monoesters were obtained with satisfactory results with a complete and controlled switch in stereoselectivity (up to 97:3 and 1:99 er). Chiral six-membered carbocyclic uracil nucleosides were generated with excellent enantioselectivities after derivatization. A series of control experiments and density functional theory (DFT) calculations supported that the reaction proceeded in a bifunctional activated manner, where the -oxide groups and N-H proton of the amides were vital for catalytic reactivity and stereocontrol. The DFT calculation also supported the distance-directed switching of enantioselectivity, in which the l-prolinamide moiety moved from the C3 to C2 position on the pyridine ring, resulting in the H-bond interaction between the amide N-H and OH group of --diol also shifted from one hydroxyl group to another.