Intramolecular TDDA Approach to the Dihydrobenzopentalene Skeleton of Aromatized Nine-Membered Enediyne Antibiotics

The tetradehydro-Diels-Alder (TDDA) reaction has recently emerged as a powerful method for the construction of polycyclic frameworks. In this study, we investigated the application of the TDDA reaction to the synthesis of the nine-membered enediyne framework found in enediyne antibiotics and its aromatized product, the tetradehydrobenzopentalene skeleton. Several TDDA precursors bearing an acetylene carboxylic acid moiety and an enyne side chain on a cyclopentene core were synthesized via two Pd-catalyzed reactions. Heating these precursors at 150 °C did not afford the expected TDDA product. However, a hetero-TDDA reaction occurred at 150 °C to give a tricyclic compound containing a pyrone moiety when the silyl ester was employed. In contrast, the precursor with interchanged side chains produced a TDDA adduct with a dihydrobenzopentalene framework, albeit in low yield upon heating at 200 °C.