Controlling cis/trans-selectivity in intramolecular Diels-Alder reactions of benzo-tethered, ester linked 1,3,9-decatrienes

Predictions from DFT (B3LYP/6-31 G(d))-computed stereoisomer product distributions for intramolecular Diels-Alder (IMDA) reactions have been successfully replicated in the laboratory. Benzo-tethered hexadienyl acrylates generally undergo moderately trans-selective IMDA reactions which, as suggested by DFT calculation, arise from two opposing transition structure (TS) features: stabilising secondary orbital interactions, which are stronger in the cis-TSs, and stabilising pi-conjugative interactions between the benzo moiety and the 1,3-diene component - which are stronger in trans-TSs. Substrates carrying a removable substituent (i.e. Br or TMS) at C3 of the diene or C12 of the aromatic ring are predicted to undergo highly cis-selective thermal IMDA reactions by steric destabilisation of the trans-TS. A substrate carrying a two atom tether between C3 and C12 is predicted to undergo a highly trans-selective intramolecular cycloaddition by destabilisation of the cis-TS. These calculations are borne out experimentally.