Stepwise synthesis of unsymmetrically substituted porphyrins: isocoproporphyrin

Abstract

Szmzmary A new, general, stepwise porphyrin synthesis in which tripyrrenes (2) and 1 ', 8'-dimethyl-a,c-biladienes (9) are crystalline and fully characterised intermediates is exemplified in the first total synthesis of isocoproporphyrin tetramethyl ester (1).

Syntheses and Functionalizations of Porphyrin Macrocycles

“…Symmetry limitations associated with the earlier a,c-biladiene syntheses were removed by development of routes to unsymmetrically substituted a,c-biladienes [14, 67, 68]. There now exists two complementary methods, which involve “clockwise” or “counterclockwise” elongation of the developing a,c-biladiene (Scheme 20 ).…”

“…There now exists two complementary methods, which involve “clockwise” or “counterclockwise” elongation of the developing a,c-biladiene (Scheme 20 ). The counterclockwise route was developed first [67] and involves catalytic hydrogenation of a benzyl tert-butyl dipyrromethane-1,9-dicarboxylate 32 to give a monocarboxylic acid 71 which reacts under mild conditions with a 2-formyl-5-methylpyrrole 65 to afford a high yield of a so-called tripyrrene salt 72 . Treatment with TFA (which serves to cleave the tert-butyl ester) and a second, different 2-formylpyrrole 73 , gives a high yield of 1,19-dimethyl-a,c-biladiene salt 74 with a completely unsymmetrical array of substituents; cyclization using, for example, the copper(II) method, followed by demetalation with concentrated sulfuric acid in trifluoroacetic acid gives the porphyrin 75 .…”

“…N -Chlorosuccinimide (NCS) [72-77] or chlorine [64, 65] are normally used for chlorination, although HCl/H 2 O 2 [78] and PhSeCl 3 [79] have also been reported. Similarly, N -bromosuccinimide (NBS) [63, 64, 67, 80-84], bromine [64, 73, 85, 86], HBr/H 2 O 2 [66, 71], copper(II) bromide [85] and PhSeBr 3 [69] have been used for bromination of porphyrin macrocycles. Polybromination can lead to mixtures of regioisomers when unsubstituted β- and meso -positions are available at the macrocycle periphery.…”

Porphycenes and Related Isomers: Synthetic Aspects

“…To overcome this obstacle, the authors adapted an early report on the use of Cu 2+ ions to perform the cyclization of appropriately functionalized biladiene-ac salts to furnish porphyrins. 182 This procedure produced a cyclization; unfortunately, the product was not the expected isoporphycene but instead the copper complex of 9- In the same report, 18 the template cyclization of dialdehyde 293 in the presence of a divalent metal 184,185…”

“…However, although many experimental conditions were tested, the acid-catalyzed condensation led only to undefined products. To overcome this obstacle, the authors adapted an early report on the use of Cu 2+ ions to perform the cyclization of appropriately functionalized biladiene- ac salts to furnish porphyrins . This procedure produced a cyclization; unfortunately, the product was not the expected isoporphycene but instead the copper complex of 9-formyloctaethylisocorrole.…”