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.

本研究成功实现了以N,N′-二氧酰胺（N,N′-dioxides）手性金属配合物为催化剂的缺电子烯烃（electron-deficient alkenes）催化不对称分子内及分子间卤代醚化反应（haloetherification），其中卤素可选用氯（Cl）、溴（Br）、碘（I）。在手性铁(III)配合物（chiral Fe(III) complex）催化下，可得到一系列四氢吡喃衍生物（tetrahydropyran derivatives），反应收率优良（最高可达99%），且对映选择性优异，对映体过量值（enantiomeric excess，ee）最高达97%。经手性铈(III)配合物（chiral Ce(III) complex）催化，可获得性能优良的手性氧杂环庚烷衍生物（oxepane derivatives）。此外，以甲醇（MeOH）作为亲核试剂（nucleophile），在钪(III)配合物（Sc(III) complex）催化下，可实现查尔酮（chalcones）的分子间卤代醚化反应。该合成方法还可成功应用于(-)-Centrolobine的合成。与此同时，本文提出了合理的反应机理（reaction mechanism）。