(<i>Z</i>)‑Selective Isomerization\nof 1,1-Disubstituted Alkenes by Scandium-Catalyzed Allylic C–H\nActivation

The isomerization of 1,1-disubstituted alkenes through\n1,3-hydrogen\nshift is an atom-efficient route for synthesizing trisubstituted alkenes,\nwhich are important moieties in many natural products, pharmaceuticals,\nand organic materials. However, this reaction often encounters regio-\nand stereoselectivity challenges, typically yielding <i>E</i>/<i>Z</i>-mixtures of the alkene products or thermodynamically\nfavored (<i>E</i>)-alkenes. Herein, we report the (<i>Z</i>)-selective isomerization of 1,1-disubstituted alkenes\nto trisubstituted (<i>Z</i>)-alkenes via the regio- and\nstereospecific activation of an allylic C–H bond. The key to\nthe success of this unprecedented transformation is the use of a sterically\ndemanding half-sandwich scandium catalyst in combination with a bulky\nquinoline compound, 2-<i>tert</i>-butylquinoline. Deuterium-labeling\nexperiments and density functional theory (DFT) calculations have\nrevealed that 2-<i>tert</i>-butylquinoline not only facilitates\nthe CC bond transposition through hydrogen shuttling but also\ngoverns the regio- and stereoselectivity due to the steric hindrance\nof the <i>tert</i>-butyl group. This protocol enables the\nsynthesis of diverse (<i>Z</i>)-configured acyclic trisubstituted\nalkenes and endocyclic trisubstituted alkenes from readily accessible\n1,1-disubstituted alkenes. It offers an efficient and selective route\nfor preparing a new family of synthetically challenging (<i>Z</i>)-trisubstituted alkenes with broad substrate scope, 100% atom efficiency,\nhigh regio- and stereoselectivity, and an unprecedented reaction mechanism.