Porphyrins with exocyclic rings. Part 21: Influence of pyrrolic and carbocyclic ring alkyl substituents on the synthesis of porphyrins bearing six-membered exocyclic rings

• Published in: Tetrahedron Vol. 61; no. 49; pp. 11628 - 11640
• Main Authors: Shiner, Craig M., Lash, Timothy D.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 05.12.2005; Elsevier
• Subjects: 4,5,6,7-Tetrahydroindoles; Chemistry; Chemistry, Organic; Cycloalkanoporphyrins; MacDonald ‘2+2’ condensation; Petroporphyrins; Physical Sciences; Pyrrole chemistry; Science & Technology; 4,5,6,7-Tetrahydroindoles; Cycloalkanoporphyrins; Pyrrole chemistry; MacDonald ‘2+2’ condensation; Petroporphyrins; petroporphyrins; RESONANCE RAMAN CHARACTERIZATION; OIL-SHALE; SEDIMENTARY PORPHYRINS; pyrrole chemistry; INFRARED-SPECTROSCOPY; MASS-SPECTROMETRY; cycloalkanoporphyrins; NICKEL(II) CYCLOALKANOPORPHYRINS; MOLECULAR FOSSILS; DEOXOPHYLLOERYTHROETIOPORPHYRIN DPEP; MacDonald '2+2' condensation; VIBRATIONAL SPECTROSCOPY; 4,5,6,7-tetrahydroindoles; FINGERPRINTING PETROPORPHYRIN STRUCTURES
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2005.10.019

A series of 5-substituted 4,5,6,7-tetrahydroindoles were prepared by reacting 4-substituted cyclohexanones with phenylhydrazones derived from esters of acetoacetic acid under Knorr-type reaction conditions. Related 6,6-dimethyltetrahydroindoles were also prepared by reacting dimedone with oximes by the Knorr pyrrole syntheses, followed by selective reduction of the remaining ketone moiety with diborane. The substituted tetrahydroindoles were regioselectively oxidized with lead tetraacetate to give the related 7-acetoxy derivatives, and these reacted with 5-unsubstituted pyrrole esters to give pyrrolyltetrahydroindoles. In one case, a bromo substituent was used to protect the β-position of the pyrrole reactant. Cleavage of the benzyl ester protective groups with hydrogen over Pd/C, which also removes the bromo-protective group, gave four dipyrrole carboxylic acids. These were condensed with a dipyrrylmethane dialdehyde using the MacDonald ‘2+2’ condensation to give substituted porphyrins with six-membered exocyclic rings. These structures are useful for comparison to porphyrin samples found in organic-rich sediments such as oil shales and petroleum. The presence of methyl substituents on the six-membered ring for the tetrahydroindole precursors slightly decreases the yields for porphyrin synthesis, and this effect is enhanced when the system becomes more sterically crowded due to the presence of an ethyl group of the adjacent pyrrole ring. 5-Alkyl substituted tetrahydroindoles were also converted to tetrapropanoporphyrins via a cyclotetramerization procedure. The alkyl substituents again decreased the yields, although 5-alkyl substituents were found to have a far less deleterious effect than 6-alkyl groups. In addition to providing samples to help assign the vibrational spectra of geoporphyrin samples, these results demonstrate that highly substituted porphyrin systems can be prepared from tetrahydroindole derivatives. Syntheses of porphyrins with substituted six-membered exocyclic rings from tetrahydroindoles have been developed. These sterically congested porphyrins were generated using the MacDonald ‘2+2’ methodology or a one step self-condensation procedure.