Regio- and Diastereoselective Annulation of α,β-Unsaturated Aldimines with Alkenes via Allylic C(sp 3 )-H Activation by Rare-Earth Catalysts.

The [3 + 2] or [4 + 2] annulation of α,β-unsaturated aldimines with alkenes via β'- or γ-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 α,β-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 α-methyl-substituted α,β-unsaturated aldimines with alkenes by a C 5 Me 4 SiMe 3 -ligated scandium catalyst took place in a trans -diastereoselective [3 + 2] annulation fashion via C(sp 3 )-H activation at the α-methyl group (β'-position), exclusively affording alkylidene-functionalized cyclopentylamines with excellent trans -diastereoselectivity. In contrast, the reaction of β-methyl-substituted α,β-unsaturated aldimines with alkenes by a C 5 Me 5 -ligated cerium catalyst proceeded in a cis -diastereoselective [4 + 2] annulation fashion via γ-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.