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.