Heavy atom effects in the Paternò–Büchi reaction of pyrimidine derivatives with 4,4’-disubstituted benzophenones

The regioselectivity and the photochemical efficiency were investigated in the Paternò–Büchi reaction of 1,3-dimethylthymine (DMT) and 1,3-dimethyluracil (DMU) with benzophenone (1b) and some 4,4’-disubstituted derivatives (dimethoxy (1a), difluoro (1c), dichloro (1d), dibromo (1e) and dicyano benzophenone (1f)) that gives rise to two regioisomeric oxetanes, 2 and 3. The regioselectivity (the ratio of 2/3) decreased gradually for both DMT/DMU photochemical systems from 1a to 1f. That is, a halogen atom as an electron-withdrawing group (EWG) has a pronounced effect on the regioselectivity. However, the photochemical efficiency of the 1e systems did not show the expected increase, but decreased relative to systems with 1b. Temperature effects on the regioselectivity of 1b–e systems showed some interesting features for systems with heavy atoms (including the 1d and 1e systems), such as higher inversion temperatures, and an entropy-controlled regioselectively whereas the regioselectivity for two other systems (1b and 1c) is enthalpy–entropy controlled. A heavy atom effect is suggested to be responsible for these unusual phenomena based on the triplet-diradical mechanism of the Paternò–Büchi reaction.