Syntheses and Spectroscopic Properties of Methylbenzoate Derivatives of Tetrabenzoporphyrin, Application to Circular Dichroism Studies

The syntheses, UV-VIS and fluorescence data of two methylbenzoate derivatives of tetrabenzoporphyrins, i.e., 5-p-methoxycarbonylphenyltetrabenzoporphyrin (TBPPhCO2Me), 5-p-methoxycarbonylphenyl-10,15,20triphenyltetrabenzoporphyrin (TPTBPCO2Me), and their zinc and magnesium complexes are described. The latter was tested as a bis(zinc-porphyrin) host in the CD-based molecular recognition studies because of its expanded surface compared to the conventional porphyrin rings and its red shifted Soret band with a large extinction coefficient. INTRODUCTION During the last few years porphyrins and metalloporphyrins have been widely used in the studies of p-p interactions, photosynthetic mimics and molecular recognition. Due to their intense red shifted Soret band, their propensity to undergo p-p stacking in a stereocontrolled manner, and facile metal incorporation, porphyrins have attracted widespread attention as reporter groups for structural studies by circular dichroism (CD) spectroscopy. The chromophore 5-(p-carboxyphenyl)-10,15,20triphenylporphyrin (TPPCOOH) has been extensively employed for structural analysis and determination of chirality following three main approaches. (i): It has been used as a reporter group for absolute configurational assignments of chiral diols with a rigid skeleton by the CD exciton chirality method. The enhanced sensitivity obtained in comparison with commonly used chromophores allows observation of exciton coupling over very large distances. (ii): Hydroxyland amino-containing chiral compounds with acyclic flexible skeletons have been converted into their bis-derivatives of Zn-(TPPCOOH). Under conditions in which the bis-derivatives undergo stereoselective intramolecular p-p stacking, the CD couplet reveals the absolute sense of twist between the porphyrins dictated by the configuration of the chiral substrate. (iii): An alternative approach requiring no porphyrin derivatization is possible for monoand bis-functionalized chiral compounds, namely, a chiral bidentate conjugate (guest) forms a host/guest complex with a bis(Zn-porphyrin)tweezer (host). The absolute configuration of the conjugate determines the absolute sense of twist between the two porphyrins by favoring a host/guest conformation where the bulkier group lies outside the complex giving rise to an exciton CD couplet. This approach has been applied to amines, 7 secondary alcohols and carboxylic acids. To further explore the use of porphyrins as CD reporter groups and to improve the CD sensitivity and chiral recognition, we are currently developing new porphyrin chromophores. We focused our attention on a subset of porphyrins bulkier than tetraphenylporphyrin and also on porphyrins expected to show stronger fluorescence for possible application in Fluorecence Detected Circular Dichroism (FDCD), a technique with generally much higher sensitivity than conventional CD. Tetrabenzoporphyrins (TBP) appeared to be good candidates because of the expanded surface compared to porphyrin and their unique spectral properties. Meso-tetraphenylsubtituted TBPs (TPTBP) exhibit large extinction coefficients (ca. 300,000) and red-shifted Soret (ca. 460 nm) and Q bands. 12 The metallated Zn and Mg TBP also show an intense and narrow Soret band (ca. 426 nm and 428 nm) in most solvents while the absorption spectrum of the free TBP (H2-TBP) is more complex. Another attractive property of TBPs is their high fluorescence compared to tetraphenylporphyrins. Literature shows that the fluorescence quantum yield depends on the geometry of the tetrapyrrole ring and on the nature of the metal forming the complex. The quantum yields of H2-TBP and Mg-TBP are 0.41 and 0.50, respectively, while that of ZnTBP is 0.11 and lower. In order to use TBPs as CD-reporter group, the presence of a phenyl substituent bearing a carboxyl group was required for derivatization of chiral molecule of interest. In this paper, the syntheses of 5-p-methoxycarbonylphenyl-10,15,20-triphenyltetrabenzoporphyrin (TPTBPCO2Me) and 5p-methoxycarbonylphenyltetrabenzoporphyrin (TBPPhCO2Me) and their spectroscopic properties are described. We also report results using dimeric (Zn-TPTBP) chromophore as a host for absolute configuration studies of chiral compounds. RESULTS AND DISCUSSION Synthesis and spectral properties of 5-p-methoxycarbonylphenyl-10,15,20triphenyltetrabenzoporphyrins and 5-p-methoxycarbonylphenyltetrabenzoporphyrins. Convenient methods for the preparation of symmetrical TBPs with functional groups have recently been reported. To prepare TPTBPCO2Me (3), we used a strategy described for the preparation of symmetrical TPTBP based on the thermal reaction of porphyrins fused with bicyclo [2.2.2]octadiene. In our case we condensed two different aldehydes with the isoindole precursor (1) prepared according to the literature. Mixed condensation between isoindole (1), benzaldehyde and methyl 4-formylbenzoate catalysed by BF3-etherate and subsequent oxidation gave a statistical mixture of zinc derivatives including 2a. Treatment of 2a with acetic acid to remove the zinc provided 2b which after retro DielsAlder reaction led to porphyrin (3) that was isolated from the mixture of compounds by chromatography with a yield of 7%. Zinc-TPTBPCO2Me (4) was readily obtained by reaction with an excess of zinc acetate with a yield of 94%. (Scheme 1)