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 Pd^II 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 Pd^II complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.