Regio- and Diastereoselective Annulation of α,β-Unsaturated Aldimines with 1,3-Dienes by Rare-Earth-Catalyzed Allylic C(sp3)−H Activation

The catalytic annulation of α,β-unsaturated aldimines with 1,3-dienes via allylic C(sp ³ ) − H activation is of great interest and importance as an efficient route for synthesizing alkenyl-functionalized cycloalkylamines but has remained undeveloped due to diverse reactivities and selectivities of these substrates. Herein, we report for the first time the regio- and diastereoselective [3 + 2] and [4 + 2] annulations of α,β-unsaturated aldimines with a wide array of 1,3-dienes via allylic C(sp ³ ) − H activation by half-sandwich rare-earth catalysts. The reactivity and selectivity diverged significantly based on subtle variations in both catalyst architecture and substrate substituents. The C ₅ Me ₄ SiMe ₃ -ligated scandium catalyst enabled the trans -diastereoselective [3 + 2] annulation of α-methyl-substituted α,β-unsaturated aldimines with 1-aryl- and 1-alkyl substituted 1,3-butadienes via β'-allylic C(sp ³ ) − H activation. Intriguingly, the diastereoselectivity was inverted to cis when reacting with less sterically hindered butadiene, isoprene, myrcene and 1,3-cyclohexadiene. The analogous C ₅ Me ₅ -ligated cerium catalyst promoted the cis -diastereoselective [4 + 2] annulation of β-methyl-substituted α,β-unsaturated aldimines with electron-rich 1-aryl-1,3-butadienes via γ-allylic C(sp ³ ) − H activation. Notably, when applied to amino-substituted 1-aryl-1,3-butadienes, the cerium catalyst enabled a stereoselective cascade involving the cis -diastereoselective [4 + 2] annulation followed by intramolecular hydroamination. This work provides an atom-efficient protocol for the divergent synthesis of a new family of alkenyl-functionalized cycloalkylamines, featuring 100% atom-efficiency, broad substrate scope and high regio- and diastereoselectivity.