Steric factors controlling regioselective and efficient <i>N</i>-methylation of β-tetrabromoporphyrins

<i>N</i>-Methylation is a facile way to tune the structures and the electronic properties of porphyrin macrocycles, which could induce molecular recognition abilities or asymmetric geometric structures for organocatalytic and optoelectronic applications. However, as <i>N</i>-methylation reactions require a strong methylating reagent such as methyl triflate, control over the reactivities including methylation number and positions is still elusive. In this work, we have achieved highly regioselective and efficient ²¹<i>N</i>,²³<i>N</i>-dimethylation of β-tetrabrominated porphyrins by methyl triflate. The experimental and theoretical evidence reveal that steric effects of bulky Br groups and unique tautomerisms of β-substituted porphyrins play essential roles in determining the regioselectivity of the nucleophilic <i>N</i>-methylation. Moreover, the high basicity of the formed ²¹<i>N</i>,²³<i>N</i>-dimethylporphyrins induces the facile protonation of imine nitrogen atoms, which regulates the number of introduced methyl groups to suppress further <i>N</i>-methylation. As Br groups can be easily converted into various types of substituents, this work provides significant insights to expand the synthetic methods of <i>N</i>-methylporphyrins with precisely tunable reactivities and physicochemical properties.