One-pot Synthesis of A2BC-Type Free Base Porphyrins

Treatment of 5,15-diarylporphyrins with a combination of organolithium and alkyl iodide reagents followed by hydrolysis with water and oxidation with DDQ gives convenient access to A 2 BC-type meso-tetrasubstituted free base porphyrins in a one-pot synthesis.Key intermediates are mesomeric phlorin-and porphodimethene-type anions, the latter one being able to react with electrophiles under thermodynamic control.The synthesis of unsymmetrically meso-substituted porphyrins, e.g., the so-called ABCD-type porphyrins remains a challenging topic in porphyrin chemistry. 1Next to total syntheses 1 substitution reactions offer good potential. 2Earlier we had shown that S N Ar reactions of nickel(II)porphyrins (1) with organolithium reagents yield reactive intermediates 3 (Meisenheimer-type 4 porphodimethene anions) which can be trapped in situ with organic electrophiles to yield A 2 BC-type disubstituted nickel(II)porphyrins (3) in a one-pot reaction (Scheme 1). 5 Similar conditions applied to the free base porphyrins (2) resulted only in mono-substitution (4) and mechanistic studies indicated a phlorin anion to be the key intermediate of this reaction.3b Thus, synthesis of A 2 BC-type free base porphyrins (5) via S N Ar reactions necessitated either two addition-oxidation sequences using two different LiR reagents 3c or first preparation of 3 followed by demetallation; the latter typically requiring harsh reaction conditions (e.g., very strong acids or BBr 3 ). 6 N NN NLiR 2 , THF, -70°C b) H 2 O c) R 3 I, 1 h, rt d) oxidation (air or DDQ) R 2 R 3 H + Scheme 1.Standard reaction of Ni(II) and free base A 2 porphyrins with R 2