Regio- and Diastereoselective Annulation of ,-Unsaturated Aldimines with Alkenes via Allylic C(sp³)-H Activation by Rare-Earth Catalysts

The [3 + 2] or [4 + 2] annulation of alpha,beta-unsaturated aldimines with alkenes via beta '- or gamma-allylic C(sp(3))-H activation is, in principle, an atom-efficient route for the synthesis of five- or six-membered-ring cycloalkylamines, which are important structural motifs in numerous natural products, bioactive molecules, and pharmaceuticals. However, such a transformation has remained undeveloped to date probably due to the lack of suitable catalysts. We report herein for the first time the regio- and diastereoselective [3 + 2] and [4 + 2] annulations of alpha,beta-unsaturated imines with alkenes via allylic C(sp(3))-H activation by half-sandwich rare-earth catalysts having different metal ion sizes. The reaction of alpha-methyl-substituted alpha,beta-unsaturated aldimines with alkenes by a C5Me4SiMe3-ligated scandium catalyst took place in a trans-diastereoselective [3 + 2] annulation fashion via C(sp(3))-H activation at the alpha-methyl group (beta '-position), exclusively affording alkylidene-functionalized cyclopentylamines with excellent trans-diastereoselectivity. In contrast, the reaction of beta-methyl-substituted alpha,beta-unsaturated aldimines with alkenes by a C5Me5-ligated cerium catalyst proceeded in a cis-diastereoselective [4 + 2] annulation fashion via gamma-allylic C(sp(3))-H activation, selectively yielding multisubstituted 2-cyclohexenylamines with excellent cis-diastereoselectivity. The mechanistic details of these transformations have been elucidated by deuterium-labeling experiments, kinetic isotope effect studies, and the isolation and transformations of key reaction intermediates. This work offers an efficient and selective protocol for the synthesis of a new family of cycloalkylamine derivatives, featuring 100% atom efficiency, high regio- and diastereoselectivity, broad substrate scope, and an unprecedented reaction mechanism.