Porphyrins with exocyclic rings. Part 10. Synthesis of meso,β-propanoporphyrins from 4,5,6,7-tetrahydro-1 H-indoles

Abstract

Benzyl ( 6) and tert-butyl 3-methyl-4,5,6,7-tetrahydro-1H-indole-2-carboxylates ( 28) were easily prepared from cyclohexanone using a variation of the Knorr pyrrole condensation. Regioselective oxidation with lead tetraacetate gave the corresponding 7-acetoxy derivatives, or related solvolysis products, and subsequent reaction with 5-unsubstituted pyrrole-2-carboxylates in the presence of p-toluenesulfonic acid in acetic acid gave a series of 7-pyrrolyltetrahydroindoles 16 in excellent overall yields. Cleavage of the protective ester units, followed by acid-catalyzed condensation with diformyldipyrrylmethanes 19 under modified MacDonald “2 + 2” conditions gave good yields of meso,β-propanoporphyrins 26. This chemistry was sufficiently versatile that a porphyrin with two six-membered exocyclic rings ( 34) could be prepared by the same methodology. On the other hand, attempts to cyclize an a,c-biladiene 37 incorporating a six-membered carbocyclic ring gave moderate to poor yields of the required meso,β-propanoporphyrin 26a, probably due to a deleterious steric interaction between the carbocyclic ring and an adjacent alkyl substituent. Nonetheless, the results described below demonstrate the value of this approach for the synthesis of sedimentary cycloalkanoporphyrins