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.