From thioether substituted porphyrins to sulfur linked porphyrin dimers: an unusual S_NAr via thiolate displacement?

Abstract

a Treatment of meso 2-ethylhexyl-3-mercaptopropionate substituted porphyrins with base at room temperature generated a porphyrin thiolate anion which in situ reacted in a nucleophilic aromatic substitution (S N Ar) reaction with remaining thioether derivative. This reaction yielded S-linked bisporphyrins in good yields, with mechanistic insight obtained via displacement reactions. Additionally, S N Ar of the thioether chain was achieved using S-and organolithium nucleophiles.Owing to their biological and medical importance, 1 the synthesis of organosulfur compounds has been the focus of thorough investigations. 2 One important development is the nucleophilic aromatic substitution (S N Ar) with the thiolate anion. 3 Typically, thiolate S N Ar only occurs with activated aryls with leaving groups such as halides or tosylates, 4 requiring a very strong base, elevated temperature and/or the use of metal catalysts. 3c,5 Additionally, it is often hindered via competing oxidation reactions to form disulfide bonds ( Fig. 1). 6 In a remarkable S N Ar, sulfur-linked porphyrin dimers were generated via a simple deprotection of a thioether appended porphyrin. While our initial goal was the synthesis of a free thiol group directly attached to the porphyrin macrocycle via base deprotection, bisporphyrin products were observed predominantly. Such sulfur linked bisporphyrins have not previously been reported and are easily produced, in contrast to other heteroatom linked porphyrin arrays which generally require many synthetic steps. 7These were generated via S N Ar by the thiolate at the meso position of the substituted porphyrin, with isooctyl-3-mercaptopropionate acting as an excellent leaving group. Substitution reactions on porphyrins are limited, 8 at best, and typically require highly specific activated systems and high temperatures. However, this room temperature in situ S N Ar of a seemingly unactivated porphyrin in such fashion represents, to the best of our knowledge, the first reaction of this type to be documented. This is somewhat reminiscent of previous work in our group, whereby using organolithium reagents a variety of substituents can be introduced to the porphyrin periphery via S N type reactions. 9Porphyrins bearing thiol and thioether substituents have a diverse range of optical applications due to their ability to form self-assembled monolayers (SAMs) on gold surfaces 10 and this attribute formed the basis for our interest in thioporphyrins. Adopting a versatile Pd-catalyzed porphyrin-sulfur bond forming reaction developed by Itoh and Mase, 11 a library of novel isooctyl-3-mercaptopropionate substituted porphyrins, so-called protected thiols, were synthesized. 12This involved a Pd-catalyzed reaction of bromoporphyrins 1a-i and the thiol 2-ethylhexyl-3-mercaptopropionate in good to excellent yields of 66-87%. These protected thiols have the potential to be used in Au-NP formulation or as a photosensitizer delivery system in PDT, 13 but our primary goal was for their use in deprotection reactions (Table 1). A...

Insights into the Synthesis and the Solution Behavior of meso‐Aryloxy‐ and Alkoxy‐Substituted Porphyrins

“…For these reasons, it is perhaps not surprising that S N Ar reactions as a tool for the preparation of C-, O-, S-and N-substituted porphyrins have recently been revisited. [1][2][3][4][5][6][7][8][29][30][31][32][33] However, most of these S N Ar reactions involve Ni II porphyrinates or amines as nucleophiles. It is well known that Ni II porphyrinates afford functionalized compounds that do not tolerate the drastic conditions of a demetallation reaction and, consequently, are not very useful for the preparation of various porphyrin complexes that are needed for the myriad practical applications.…”

meso‐to‐meso Sulfide‐ and Disulf­ide‐Bridged Subporphyrin Dimers

“…Contrastingly, SSbridged dimer 6 showed a broad but nonsplit Soret-like band, no fluorescence, and very fast S 1 decay with a lifetime of 4 ps, which indicated the presence of a rapid decay channel. [12] Owing to these results, and inspired by two recent reports of sulfur-bridged dimers of porphyrin [13] and BODIPY, [14] meso-to-meso sulfide (S)-bridged and disulfide (SS)-bridged subporphyrin dimers 4 and 6 (Scheme 1) were targeted as the first subporphyrin dimers peripherally bridged by heteroatoms. In contrast, μ-oxo, [6] μperoxo, [11] and complementally bridged dimers [4] were synthesized by axial-ligand exchange, and they showed small electronic interactions between the subporphyrin units.…”

Synthesis of Diazepine-fused Porphyrinoids and Annulated Porphyrin Arrays

“…Porphyrins 1a-f [13,21], 9 and 10 [13] were synthesized according to previously reported methods [22]. was then heated at 110 °C for 24 h. Upon reaction completion, the solvent was removed under reduced pressure.…”