Substituent effects on the regioselectivity of the Paternò–Büchi reaction of 5- or/and 6-methyl substituted uracils with 4,4′-disubstituted benzophenones

Abstract

The [2 + 2] photochemical cycloadditions (the Paternò–Büchi reaction) of 5- or/and 6-methyl substituted uracil derivatives with 4,4′-disubstituted benzophenones generate two series of regioisomeric oxetanes, 3 and 4. The regioselectivity (3/4) and the photochemical efficiency are strongly dependent on methyl substituent(s) at the C5–C6 double bond of the uracils. The more the methyl groups at the C5–C6 double bond, the higher the efficiency. The regioselectivity (3/4) ranges from ca. 20 : 80 for 1,3,6-trimethyluracil (1C) to ca. 80 : 20 for 1,3,6-trimethylthymine (1D). The substituent effects would derive from the hyperconjugation of the methyl group(s) at C5 or/and C6 of the uracils, which influences the stability of intermediary triplet 1,4-biradicals and the nucleophilicity of C5 and C6 sites of the double bond. Computational studies reveal that potential energies of triplet 1,4-biradicals forming oxetanes 3, BR5, are 1–4 kcal mol⁻¹ higher than those of 1,4-biradicals forming oxetanes 4, BR6, and electron densities at C5 are 0.1–0.3 unit higher than those at C6, of the double bond of the uracils, i.e. BR5 are less stable than BR6, and BR5 form more easily than BR6. Temperature effects on the regioselectivity of the Paternò–Büchi reaction of 1D with three benzophenones (2a–c) reveal that efficiencies of oxetanes 3 are higher at a lower reaction temperature, and efficiencies of 4 are higher at a higher temperature. Therefore, triplet biradicals BR5 and BR6 would be regarded as intermediates of kinetic control and thermodynamic control, respectively.