Atropisomers of meso tetra (N-mesyl pyrrol-2-yl) porphyrins: Synthesis, isolation and characterisation of all-pyrrolic porphyrins.

Atropisomerism has been observed in a variety of biaryl compounds and meso -aryl substituted porphyrins. However, in porphyrins, this phenomenon had been shown only with o -substituted 6-membered aromatic groups at meso -position. We show here for the first time that a 5-membered hetero aromatic ( N -mesyl-pyrrol-2-yl) group at meso -position leads to atropisomerism. In addition, we report a 'one-pot' synthetic route for the synthesis of 'all-pyrrolic' porphyrin (APP) with several N -protection groups (Boc, Cbz, Ms and Ts). Among these groups, we found that only the Ms group gave four individually separable atropisomers of meso -tetra ( N -Ms-pyrrol-2-yl) porphyrin. Furthermore, the reductive removal of Cbz- was achieved to obtain meso -tetra (pyrrol-2-yl) porphyrin. Thus, our synthetic procedure provides an easy access to a group of APPs and stable atropisomers, which is expected to expand the application of novel APP-based materials.

We are interested in exploring as uitable 'one-pot' method for the synthesis of tetra(N-protected pyrrol-2-yl) porphyrins. In addition, by choosing av ariety of N-protection groups for the pyrrole-2-aldehyde,w ew ished to exploret he formationo f atropisomers, and their isolation.H erein, we report successful procedures towards those APPs, and the isolation and characterization of stable atropisomers.

Results and Discussion
For the synthesis of APP 3,w ee nvisaged to apply 'one-pot' tetramerization procedures. Amongs everal knownm ethods, we chose to explore NH 2 OH·HCl mediatedc ondensation, as it was successfully appliedt omeso tetra(theinyl-2-yl) porphyrin synthesis. [21] In addition, the broadly applicable Lindsey's method, using catalytic BF 3 ·OEt 2 , [18] and ar ecently reported reaction using p-toluenesulfonic acid (pTSA) in hot DMF were selected. [22] As in the synthesiso f2,N -alkylated (Me, iPr) pyrrole-2-aldehydes (4-Me, 4-iPr) were explored in former two conditions. However,t hey did not yield any product, and only starting materials were observed. We assumed that the Lewis acid activated formyl group was stabilized by the electron-rich nature of pyrrole, suppressingf urtherr eactiont owards the condensation. Thus, we anticipated that removal of electron density from the pyrrole-2-aldehyde could enhancet he tendency for the condensation reaction.
[c] Combined yield of all atropisomers.
highly unsymmetrical spectrum,l ikely corresponding to the aabb-isomer.T he final polar fraction (F4) showed as ymmetric (F1-like) spectrum, with ab roadened s CH signalo ft he por-phyrin at d = 8.95 ppm (width = 36 Hz in 600 NMR);t his lead us to assign it as an aaab-isomer.T he ratio of atropisomers, based on the isolated yields, was found to be 5.9:3.7:2.9:1 (F1:F2:F3:F4). The stabilityo ft he atropisomers was furtheri nvestigated by variable temperature (VT) NMR in toluene-d6 (FiguresS27 to S30, Supporting Information). Heating the solutions up to 80 8Cr endered no change in their respective signal pattern (Figures S26-S29). When the F3 was further heatedt o1 00 8C, for 4h,s ome isomerization was observed ( Figures S16 and  S30, Supporting Information). This confirms that the atropisomerso f3c-2H are highly stable and possess ah igh isomerization energy barrier.
In the next step, to prove the inherentm etal-complexation ability of APP, N-sulfonyl (pyrrolyl-2-yl)p orphyrins (3c-2H, 3d-2H) were metallated with Zn II and Ni II acetate in hot DMF.T he resultingm etallo-APPs showed the characteristic Qb and peaks at 554 nm with as houlder at 590 nm for 3c-Zn,a nd at 534 nm with ashoulder at 567 nm for 3c-Ni (Figure 4).
With metallated 3c-Zn, 3c-Ni and 3d-Zn, 3d-Ni in hand, deprotection was carried out using NaOH in THF/MeOH (4:1)a nd CH 2 Cl 2 /MeOH (5:1). The reactions were stirreda t2 0 8Cu nder protection from light for up to 72 h; however,n or eactionw as observed. By refluxing the same mixture, ag reenish product was obtained. 1 HNMR (in CD 2 Cl 2 )o ft he dry mixtures indicated the formation of ap olymericm aterial. Even under exclusion of oxygen the same resultswere obtained.
To further explore the feasibility of deprotection of APPs under neutral conditions, N-Cbz removal in 3b-2H (using a mixture of inseparable atropisomers) was studied using 5% Pd/C and H 2 (1 atm.) in THF/MeOH.F rom this we could identify highly symmetric meso-tetra(pyrrol-2-yl) porphyrin (3e-2H), albeit isolated in protonated form ( Figure S36, Supporting Information). However,d irectly after removing the solvents, no protonation wasobserved in the reactionmixture as confirmed by 1 HNMR (CD 3 OD) ( Figure S35, Supporting Information). Therefore, the protonation might have occurred during the purificationu sing CH 2 Cl 2 /MeOH. Further spontaneous polymerization of unprotonated electron-rich 3e-2H was evaluated in   an oxygen environment by 1 HNMR (in CD 3 OD). The 3e-2H was found to be stable even after storing the solutionf or 90 days at room temperature;h owever,t he polymerization was observed when it was heated. Therefore, selective polymerization to make size-specific polymericA PP is possible using tetra(pyrrol-2-yl) porphyrin, which is currentlyb eing explored.

Conclusions
Herein, we reportg enerally applicable synthetic methods for the preparation of different meso tetra(N-protected pyrrol-2-yl) porphyrins (APPs). It was found that an electron-withdrawing group at the N-position in pyrrol-2-aldehyde was essential for tetramerization to yield APPs. Among the explored conditions, the Lindsey's method with N-Cbz pyrrol-2-aldehyde gave 50 %, and the NH 2 OH·HCl mediated condensation with N-Ms pyrrol-2-aldehyde gave 48 %o fr espective APPs. In addition, the N-Ms pyrrol-2-aldehyde gave stable and separable four atropisomers of tetra(N-Ms pyrrol-2-yl) porphyrin. These hitherto inaccessible all-pyrrolic porphyrins were metallated with transition metals. The metallo APPs possess similar photophysical characteristics to meso tetra aryl porphyrins. The high reactivity of the meso (pyrrol-2-yl) group in porphyrin, upon removalo fp rotection group, is au seful feature for the preparation of pyrrole-pyrrole-bridged porphyrin sheets and nanoparticles, which is currently under investigation.