Steric factors controlling regioselective and efficient N-methylation of β-tetrabromoporphyrins

Abstract

N-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 N-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 ²¹N,²³N-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 N-methylation. Moreover, the high basicity of the formed ²¹N,²³N-dimethylporphyrins induces the facile protonation of imine nitrogen atoms, which regulates the number of introduced methyl groups to suppress further N-methylation. As Br groups can be easily converted into various types of substituents, this work provides significant insights to expand the synthetic methods of N-methylporphyrins with precisely tunable reactivities and physicochemical properties.