Catalytic Asymmetric Intra- and Intermolecular Haloetherification of Enones: An Efficient Approach to (−)-Centrolobine

A catalytic asymmetric intra- and intermolecular haloetherification of electron-deficient alkenes (halogen = Cl, Br, I) has been realized by the use of chiral metal complexes of N,N′-dioxides. In the presence of a chiral Fe­(III) complex, a series of tetrahydropyran derivatives were obtained in good yields (up to 99% yield) with a high level of enantioselectivities (up to 97% ee). Promoted by a chiral Ce­(III) complex, chiral oxepane derivatives could be given in good results. Moreover, the intermolecular haloetherification of chalcones catalyzed by Sc­(III) complex using MeOH as nucleophile is demonstrated. This methodology also can be successfully applied to the synthesis of (−)-Centrolobine. Meanwhile, a reasonable reaction mechanism was proposed.

本研究借助N,N′-二氧化物（N,N′-dioxides）手性金属配合物，成功实现了以氯（Cl）、溴（Br）、碘（I）为卤源的缺电子烯烃催化不对称分子内及分子间卤代醚化反应。在手性铁(III)（Fe(III)）配合物催化下，可获得一系列四氢吡喃衍生物，产物产率优良（最高可达99%），对映选择性优异（最高达97% ee，对映体过量值）。在手性铈(III)（Ce(III)）配合物介导下，可得到性能优良的手性氧杂环庚烷衍生物。此外，本研究还证实了在钪(III)（Sc(III)）配合物催化下，以甲醇（MeOH, methyl alcohol）作为亲核试剂的查尔酮分子间卤代醚化反应。该合成策略还可成功应用于(-)-Centrolobine的合成。同时，本研究提出了合理的反应机理。