Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems

An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD‐NH2) and PdII complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ6‐protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD‐NH2 catalyst and the branched chain of the substrate, hydrogen‐bonding interactions between the N−H of the enamine motif and the C=O of the directing group MQ, and the counterion of the PdII complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations. We developed a novel SPD‐NH2 organocatalyst that works cooperatively with a PdII complex to catalyze the asymmetric intramolecular hydroalkylation. It demonstrates great reactivity, enantio‐ and diastereoselectivity (up to 99 % ee and 20 : 1 dr). Moreover, bridged or fused bicyclic systems can be conveniently transformed into diverse di‐, tri‐, and tetracyclic scaffolds for further conversion into biologically important compounds.