Fourth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-4), www.mdpi.org/ecsoc-4.htm, September 1-30, 2000

[C0029]

Conformationally Designed Biomimetic Macrocycles - Synthesis of Porphyrins and Porphodimethenes with Mixed Substitution Pattern and Distortion Modes

Institut für Chemie, Organische Chemie, Freie Universität Berlin, Takustrasse 3,D-14195 Berlin, Germany
E-mail: [email protected] und [email protected]

Received: 14 August 2000 / Uploaded: 16 August

In order to gain a better insight into these processes and to firmly establish conformational control as one process for the regulation of the macrocycle properties a multitude of synthetic model compounds have been studied. ^[2] Nonplanar aromatic systems are accessible by synthesis of sterically strained systems and thus highly substituted porphyrins have been used prominently in this area.^[2,9] So far most studies have been concerned with simple symmetric porphyrins.^[2] Important examples, are 2,3,7,8,12,13,17,18-octaalkyl-5,10,15,20-tetraarylporphyrins (e.g. 1), ^[10] 2,3,5,7,8,10,12,13,15,17,18,20-dodecarylporphyrins,^[11] 2,3,5,7,8,10,12,13,15,-17,18,20-dodeca-alkylporphyrins,^{[10b,11b,12,13]} 2,3,7,8,12,13,17,18-octahalogeno-5,10,15,20-tetraarylporphyrins, ^[10c,14] and 5,10,15,20-tetraalkylporphyrins.^[15] Such porphyrins are easily accessible by condensation of 3,4-disubstituted pyrrole with the appropriate aldehyde or via halogenation of 5,10,15,20-tetraphenylporphyrin.^[16]

While for b substituent mixing synthetic strategies are in principle available a rational synthesis of porphyrins with different regiochemical arrangement of meso substituents was not possible until recently. Existing methods utilized either only theoretically possible multi-step total syntheses or mixed condensations of pyrroles and aldehydes requiring an inordinate laborious chromatographic work-up.^[16] This lack of synthetic methodology has now been overcome with our development of the use of organolithium reagents for the meso functionalization of tetrapyrroles. ^[13a,17] The reaction of porphyrins with LiR proceeded via an addition-oxidation mechanism and allowed the meso substitution of porphyrins in excellent yields. Here we report that this reaction can be utilized for the synthesis of conformationally designed porphyrins with different type and number of meso substituents (2) with defined regiochemical arrangement and describe structural studies aimed at elucidating the conformational behavior of porphyrins with mixed distortion modes. An overview of the synthetic strategy is given in Scheme 1.

To investigate the correlation between the conformation of the macrocycles and its physicochemical properties, porphyrins with mixed meso substituent types are of special interest. The structures of S₄ symmetric dodecasubstituted, nonplanar porphyrins are well known. Meso alkyl groups lead to a ruffled distortion mode and aryl groups induce a saddle type conformation. As natural tetrapyrrole systems exhibit asymmetric substituent pattern the question arose to what extent a mixing of distortion modes can be achieved by rational variation of the meso-substituent pattern. We planned to synthesize porphyrins with different types and numbers of both meso alkyl and aryl substituents to investigate this problem.

The initial studies had shown that all meso positions can be substituted with LiR using four successive addition-oxidation cycles.^[13a,18] Thus it should be possible to synthesize regiochemically pure porphyrins with different type and number of meso substituents by choosing the appropriate sequence for the individual LiR reagents. As described above, meso alkyl and meso aryl substituents flanked by b alkyl or aryl residues give rise to different distortion modes. Thus we chose BuLi and PhLi as standard reagents to test the feasibility of this approach. Octaethyl-porphyrin and its metal complexes were used as educts as a large body of structural data is available for highly substituted porphyrins that incorporate the octaethylporphyrin (7) motif.^[2] For ease of NMR spectroscopic detection and as many comparative structural data are available for nickel(II) complexes most of the test reactions were performed using (2,3,7,8,12,13,17,18-octaethylporphyrinato)nickel(II) (3) as starting compound.

With this new method mixed aryl and alkyl substituents could be introduced in various regio chemical combinations and high yields by use of the respective organolithium reagents. For example, by repetition of the sequence shown in Scheme 1 with different residues (R = n-butyl or phenyl), four dodecasubstituted porphyrins (9, 10, 11, 12) with mixed substitution pattern were successfully prepared, indicating the synthetic utility of this reaction.

As one example the structure of an undecasubstituted nickel(II) porphyrin is shown in Figure 1. The structure exhibits an overall saddle distortion with significant displacements of the alkyl substituted meso position. Thus, a mixing of distortion modes occurs in compounds of this type.

As described above treatment of NiOEP with BuLi gives an anion that potentially can be trapped with electrophiles. Thus, an alkyl iodide was added to the mixture containing the anionic species. When NiOEP was used as educt the reaction resulted in the formation of porphodimethenes (13), which could not be oxidized with DDQ, an indication of the validity of the proposed mechanism.