Amination of meso-bromophenyl(polyalkyl)porphyrins: Synthesis of porphyrins containing a hydroxypiperidine fragment

Abstract

5,15-Bis(4-bromophenyl)-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin and 5-(4-bromophenyl)-13,17-dibutyl-2,3,7,8,12,18-hexamethylporphyrin were synthesized, and their palladium-catalyzed amination with a number of cyclic secondary amines, including hydroxypiperidines, was studied [Pd(OAc)2, ligand, THF or dioxane, t-BuONa, 80–100°C]. The reactions of the meso-bromophenylporphyrins with piperidine and morpholine gave the corresponding amination products in quantitative yield. The amination with hydroxypiperidines required excess amine (3 equiv per bromine atom) and excess base (6–8 equiv) and was accompanied by formation of hydrodebromination products; in the reactions with the bis(bromophenyl)derivative, mixed products resulting from amination at one phenyl group and reductive debromination at the other were also formed. The yields of the amination products varied from good {75–50% in the reactions with 4-hydroxypiperidine and trans-3-hydroxy-4-[4-(2-fluorophenyl)piperazin-1-yl]piperidine} to moderate (20–50%, 3-hydroxypiperidine) and poor [11–25%, trans-3,4-dihydroxypiperidine and trans-3-hydroxy-4-(4-hydroxypiperidin-1-yl)piperidine].