The Dithianyl Group as a Synthon in Porphyrin Chemistry: Condensation Reactions and Preparation of Formylporphyrins under Basic Conditions Mathias O. Senge,* ,² Sabine S. Hatscher, ² Arno Wiehe, ‡ Katja Dahms, ² and Andrea Kelling ² Institut fu ¨r Chemie, UniVersita ¨t Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Golm, Germany, and Institut fu ¨r Chemie, Organische Chemie, Freie UniVersita ¨t Berlin, Takustr. 3, D-14495 Berlin, Germany Received August 7, 2004; E-mail: mosenge@chem.uni-potsdam.de Despite an increasing number of technical, biomedicinal, and chemical applications of porphyrins, only few methods exist to introduce functional groups at the meso positions of the macrocycle. 1a Newer developments are transition metal-catalyzed coupling reac- tions requiring use of halogenoporphyrins 1b and S N Ar reactions using strong nucleophiles. 1c Historically, S E Ar reactions have been used widely, notably Vilsmeier formylation and related reactions. 2 Formylporphyrins are excellent precursors for subsequent trans- formations; however, their utility is rather limited, as formylation requires use of acidic conditions and works well only with Ni II or Cu II complexes and introduction of a CHO group deactivates the system toward further formylations. Thus, no practical methods exists for meso-polyformylporphyrins. 3 To overcome these limita- tions we have developed a new synthetic concept for functionalized porphyrins using the 1,3-dithianyl residue as a synthon in porphyrin chemistry. Current progress 1a toward unsymmetrically substituted tetra- pyrroles, both with condensation or substitution methods, offers the possibility to introduce functional groups in a strategic and regiochemical manner provided that appropriate synthons are available. 4 A classic synthon is the 1,3-dithiane-2-yl residue developed by Seebach and Corey. 5 Derivatives thereof are useful acyl anion equivalents and were used both as a functional and protected formyl group. 6 Thus, the lithio derivative of 1 offers the possibility to introduce latent formyl groups under nucleophilic instead of electrophilic conditions. The dithianyl synthon can be used in two different strategies for the preparation of novel porphyrins. 7 First, reaction of 1 with DMF yields the aldehyde 2, 8 which we have used as a key building block for porphyrins via condensation reactions (Scheme 1). 9 Aldehyde 2 can be converted in quantitative yield into the dipyrromethane 3, 10a which in turn is a useful building block for various condensa- tions. Depending on the other reactants or the reaction conditions, 2 was used to prepare porphyrins with two to four dithianyl residues. For example, a 3 + 1 condensation gave the 5,10-disubstituted derivative 4 in low yield, 10b while the 5,15-derivative 5 was obtained by reaction with dipyrromethane and TFA catalysis in 16%. More complicated were reactions aimed at the preparation of the seemingly simple 5,10,15,20-tetrasubstituted porphyrin 7. Standard condensations, for example, reaction of 3 with 2 or reaction of 2 with pyrrole under BF 3 ‚OEt 2 catalysis, afforded the 5,10,15-trisubstituted porphyrin 6 in 56% yield, each. Presumably, the target compound 7 is rather unstable. Related fragmentation reactions for nonporphyrinic systems have thus far been observed only in mass spectrometric studies. 11 However, 7 is accessible from 2 and pyrrole by using traces of BF 3 followed by neutralization with NEt 3 to afford the 5,10,15,20-tetrakis(1,3-dithianyl)-porphy- rinogen in 53% yield. Subsequent oxidation with DDQ followed by rapid workup gave 7 in 15% yield with respect to 2. Isolated 7 rapidly decomposed in solution in the presence of traces of acid and air under intermediary formation of 6. 12 Porphyrins with both meso alkyl/aryl and dithianyl groups are much more stable. For example, standard 2 + 2 condensation reactions gave porphyrin 12 with two dithianyl residues ac- companied by 10 (due to scrambling) in low yields (Scheme 2). These compounds and those having not more than two dithianyl groups are reasonably stable toward chemical transformations. For example, 10 could be metalated with zinc acetate at room temperature in 60% yield and demetalated with BBr 3 in 50% yield. 14 Our initial results on the dethioacetylation 15 reactions mimic these stabilities. While 10 and 12 could be quickly and quantitatively converted into the formylporphyrins 11 and 13 using DDQ, 16a all attempts with 6 or 7 gave only partial deprotection and complex ² Universita ¨t Potsdam. ‡ Freie Universita ¨t Berlin. Scheme 1. Synthesis of 1,3-Dithianylporphyrins via Condensation Reactions a a Conditions: (a) n-BuLi, THF, -78 °C, 1 h; then -10 °C, DMF, 2 h; then 0 °C, 16 h; then ice, 85%. (b) Pyrrole, BF3‚OEt2, rt, 40 min, then NaOH, 96%. (c) CH2Cl2, tripyrrane, pyrrole, 45 min, rt; then TFA, rt, 16 h; then DDQ; then NEt3, 3%. (d) CH2Cl2, dipyrromethane, TFA, 14 h, rt; then DDQ, 10 min, reflux, 16%. (e) CH2Cl2, pyrrole, BF3‚OEt2, 1 h, rt; then NEt3, DDQ, 4 min, 15%. (f) CH2Cl2, pyrrole, BF3‚OEt2, 1 h, rt; then excess DDQ, 1 h, 46%. (g) CHCl3, 8 equiv of bis(trifluoroacetoxy)iodo- benzene (BTIB), 45 °C, 30 min, 62%. (h) CHCl3, 4 equiv of BTIB, rt, 30 min, 30%. Published on Web 10/05/2004 13634 9 J. AM. CHEM. SOC. 2004, 126, 13634-13635 10.1021/ja045223u CCC: $27.50 © 2004 American Chemical Society