(Z)-Selective Isomerization of 1,1-Disubstituted Alkenes by Scandium-Catalyzed Allylic C–H Activation

Abstract

The isomerization of 1,1-disubstituted alkenes through 1,3-hydrogen shift is an atom-efficient route for synthesizing trisubstituted alkenes, which are important moieties in many natural products, pharmaceuticals, and organic materials. However, this reaction often encounters regio- and stereoselectivity challenges, typically yielding E/Z-mixtures of the alkene products or thermodynamically favored (E)-alkenes. Herein, we report the (Z)-selective isomerization of 1,1-disubstituted alkenes to trisubstituted (Z)-alkenes via the regio- and stereospecific activation of an allylic C–H bond. The key to the success of this unprecedented transformation is the use of a sterically demanding half-sandwich scandium catalyst in combination with a bulky quinoline compound, 2-tert-butylquinoline. Deuterium-labeling experiments and density functional theory (DFT) calculations have revealed that 2-tert-butylquinoline not only facilitates the C═C bond transposition through hydrogen shuttling but also governs the regio- and stereoselectivity due to the steric hindrance of the tert-butyl group. This protocol enables the synthesis of diverse (Z)-configured acyclic trisubstituted alkenes and endocyclic trisubstituted alkenes from readily accessible 1,1-disubstituted alkenes. It offers an efficient and selective route for preparing a new family of synthetically challenging (Z)-trisubstituted alkenes with broad substrate scope, 100% atom efficiency, high regio- and stereoselectivity, and an unprecedented reaction mechanism.