Enantioselective oxa-Diels–Alder Sequences of Dendralenes

Diene-transmissive hetero-Diels–Alder sequences involving carbonyl dienophiles are reported for the first time. High enantioselectivities are achieved in the reaction of phenylglyoxal with a broad range of dendralene structures, through the optimization of a Pd²⁺ catalyst system. The initial catalyst-controlled enantioselective oxa-Diels–Alder (ODA) cycloaddition to a [3]dendralene generates a dihydropyran carrying a semicyclic diene. This participates in a subsequent catalyst or substrate-controlled Diels–Alder reaction to generate sp³-rich fused polycyclic systems containing both heterocycles and carbocycles. Computational investigations reveal a concerted asynchronous mechanism. π-Complexation of a diene C=C bond to Pd²⁺ occurs in both the pre-transition state (TS) complex and in cycloaddition TSs, controlling stereoselectivity. A formal enantioselective [4+2]cycloaddition of a CO₂ dienophile is demonstrated.