MACROCYCLIC MODIFICATION USING ORGANOMETALLIC METHODOLOGIES - REGIOCHEMICALLY CONTROLLED MONO-HOMOLOGATION AND BIS-HOMOLOGATION REACTIONS OF PORPHYRINOGEN WITH CARBON-MONOXIDE ASSISTED BY EARLY TRANSITION-METALS

The homologation of a pyrrole to a pyridine ring within the porphyrinogen skeleton was achieved with high selectivity, good yield, and controlled regiochemistry and was scaled up to multiple gram quantities. The homologation of meso-octaethylporphyrinogen to meso-octaethyltris(pyrrole)-monopyridine was carried out by reacting carbon monoxide with Zr-C and Zr-H functionalities supported by the meso-octaethylporphyrinogen ligand [Et(8)N(4)H(4)]. The starting materials [(eta(5)-eta(1)-eta(5)-eta(1)-Et(8)N(4))Zr(mu-NaH)](2) (2) and [(eta(5)-eta(1)-eta(5)-eta(1)-Et(8)N(4))Zr(mu-KH)](2) (3) have been obtained by a direct addition of alkali hydrides to [(eta(5)-eta(1)-eta(5)-eta(1)-Et(8)N(4))Zr(THF)] (1) or via hydrozirconation reactions in the cases of [{(eta(5)-eta(1)-eta(1)-eta(1)-Et(8)N(4))ZrCH2CH3}(2)(mu-K)(2)] (6) and [{(eta(5)-eta(1)-eta(1)-eta(1)-Et(8)N(4))ZrCH=CH2}(2)(mu-K)(2)] (7). The reaction of 3 with carbon monoxide led to the intermediate formation of an eta(2)-formyl group possessing significant carbenium ion character, which was displayed in its addition to a pyrrole unit to give a pyridine ring in [{(eta(5)-eta-(1) eta-(5) eta-(1)Et(8)-(C4H2N)(3)C5H3N)Zr= O)(2)(mu-K)(2)] (4) The overall result is the formation of a novel macrocycle containing three pyrroles and one pyridine unit binding a zirconyl fragment derived from a complete cleavage of a C-O multiple bond. A straightforward hydrolysis of 4 with H2O gave a high yield of the free macrocycle [Et(8)(C4H2NH)(3)(C5H3N)] (5). The carbonylation of 6 and 7 allowed the determination of the regiochemistry of the homologation reaction which gave, upon hydrolysis of the corresponding zirconyl complex, the following free macrocycles [Et(8)(C4H2NH)(3)(3-RC(5)H(2)N)] [R = CH2CH3, 8; R = CH=CH2, 9]. The intermediate eta(2)-acyl homologates one of the pyrroles to a m-alkylpyridine ring. By this methodology we are able to introduce functionalizable substituents into the pyridine ring, i.e., in 9. General procedures are reported for one-pot large-scale synthesis of free trispyrrole-monopyridine macrocycles. The reaction of [(eta(5)-)eta(1)-eta(1)-eta(1)-Et(8)N(4))Nb-Me] (12) with carbon monoxide led to the oxoniobium(V) complex [{eta(5)-eta(1)-eta(1)-eta(1)-Et(8)(C4H2N)(3)(p-MeC(5)H(2)N)}Nb=O] (13) due to the carbenium ion properties of the intermediate eta(2)-acetyl derivative. Complex 13 contains the meso-octaethyltrispyrrole-monopyridine trianion derived from the homologation of one of the pyrrole rings of [Et(8)N(4)H(4)] into p-methylpyridine. The formation of a para-substituted pyridine is ascribed to the eta(3) bonding mode of one of the pyrrolyl anions. The homologation of the trispyrrole-monopyridine macrocycle [Et(8)(C4H2NH)(3)(C5H3N)] (7) to the bispyrrole-bispyridine macrocycle has been achieved using a sequence which involves the key hafnium derivative [{eta(5)-eta(1)-eta(5)-eta(1)-Et(8)(C4H2N)(3)(C5H3N)}Hf-Me] (17). The reaction of 17 with carbon monoxide provides the homologation of a further pyrrolyl anion into m-methylpyridine, giving the cis-bispyridine-bispyrrole macrocycle binding the oxohafnium(IV) unit in [cis-Et(8)(C4H2N)(3)(C5H3N)(m-MeC(5)H(2)N)Hf=O] (18). The hydrolysis of 18 freed the ligand [Et(8)(C4H2NH)(2)(C5H3N)(m-MeC(5)H(2)N)] (19) which was characterized by an X-ray analysis. Crystallographic details: compound 8 is triclinic, space group P $($) over bar$$ 1, a = 13.763(3) Angstrom, b = 14.464(2) Angstrom, c = 19.276(3) Angstrom, alpha = 82.77(1)degrees, beta = 89.71(2)degrees, gamma = 76.52(1)degrees, Z = 2, and R = 0.045. Compound 13 is monoclinic, space group C2/c, a = 29.380(5) Angstrom, b = 13.367(4) Angstrom, c = 40.862(7) Angstrom, alpha = gamma = 90 degrees, beta = 107.55(2)degrees, Z = 16, and R = 0.047. Compound 17 is monoclinic, space group P2(1)/n, a = 11.459(3) Angstrom, b = 13.140(3) Angstrom, c = 23.454(4) Angstrom, alpha = gamma = 90 degrees, beta = 102.23(3) Angstrom, Z = 4, and R = 0.026. Compound 19 is monoclinic, space group P2(1)/n, a = 13.038(3) Angstrom, b = 18.859(3) Angstrom, c = 14.805(3) Angstrom, alpha = gamma = 90 degrees, beta = 102.80(2)degrees, Z = 4, and R = 0.057.