For aliphatic substituted 1H-2-benzo [c]oxocins (e.g., R = Me in Scheme 1), the total energy barrier for conversion of a to d is similarly high (Scheme 2, +29.0 kcal mol -1 for R = Me, and +28.5 kcal mol -1 for R = Ph). However, thermal ring-opening of b to a' for R = Me has an even higher DFTcomputed barrier (+29.9 kcal mol -1 , see Scheme 1). While these relative DFT barriers are in qualitative agreement with the experimental results, the TS4 barrier for R = Me might be underestimated, as the experimental barrier for the ring-opening of 13b to 13a' is too high to be overcome by heating at temperatures low enough to prevent unselective decomposition, thus inhibiting the ringopening switching process of 1H-2-benzo [c]oxocins with aliphatic substituent.