Correction: UO22+-mediated ring contraction of pyrihexaphyrin: synthesis of a contracted expanded porphyrin-uranyl complex

Correction for ‘UO22+-mediated ring contraction of pyrihexaphyrin: synthesis of a contracted expanded porphyrin-uranyl complex’ by James T. Brewster et al., Chem. Sci., 2019, 10, 5596–5602.


Introduction
Metalloporphyrins and ostensibly related corrin species are central to a variety of biochemical processes essential for life. [1][2][3] Not surprisingly, the biosynthetic pathways and function of these and related conjugated tetrapyrrolic species remain a topic of fundamental interest. [4][5][6] Insights obtained from model systems have helped elucidate the molecular origins of naturally occurring tetrapyrroles while synthetic analogues, such as corrole and amethyrin ( Fig. 1), have revealed unique chemical and spectroscopic features not seen in the case of naturally occurring tetrapyrroles. [7][8][9][10][11][12][13][14][15] A recent research focus has involved probing the inuence of modied heterocyclic constituents within expanded and contracted porphyrins. 16 Obtaining such species generally requires dedicated synthetic efforts wherein key precursors are constructed with structural components of the target in mind (Fig. 1). 17,18 Nature uses uroporphyrinogen III, a common porphyrin precursor, to prepare the structurally unique corrin core found in cobalamin (vitamin B 12 ) (Scheme 1). 20 Within this biosynthetic sequence, an incipient cobalt-corrin complex facilitates ring contraction. 21 Biomimetic ring contractionoxidation approaches involving porphyrin starting materials have allowed for the construction of substituted corroles. 18,19 An early route by Johnson and co-workers utilized sulfur extrusion from thiaphlorins to yield corrole, oen in good yields. 22 However, the requisite sulfur-based starting materials are unstable, which limited the effectiveness of this approach. More recent examples have further mimicked nature by using a metal-mediated strategy, wherein a metalloporphyrin undergoes ring contraction. [23][24][25] Expanded porphyrins, species containing a larger internal cavity, have received considerable attention in recent years. [26][27][28][29] Modication of coordinating moieties within the internal lacuna has provided a number of systems displaying rich coordination chemistry and extended conjugation pathways. However, expanded porphyrins displaying meso-reactivity are rare. Early on Sessler and co-workers reported meso-activation of sapphyrin, wherein U(VI)O 2 2+ coordination enabled addition of methanol and dearomatization. 30 Continued efforts by the groups of Yoneda and Neya have shown that metallation of sapphyrin with Ag(I) results in a structural rearrangement with attendant incorporation of two methanol molecules into a neoconfused sapphyrin core. 31 A recent example by Osuka and coworkers demonstrated that water can insert into the mesoposition of hexaphyrin (1.1.1.1.1.1) upon Cu(II)or Ni(II)-metallation. 32 Setsune and co-workers have also reported that dipyriamethyrin can undergo meso-selective nucleophilic addition with cyanide, amines, and alkoxides. 33 Elegant demonstrations of ring contraction have been observed by the Furuta group with N-confused dihydrosapphyrin to give neo-confused corrole, 34 as well as by Maruyama, Fujita, Osuka, and co-workers with bis-Cu(II)octaphyrin to give Cu(II)-porphyrin. 35 Similar chemistry has been applied by both groups in other selected systems. 36 Metal-mediated contractions have also been reported by Latos-Grażyński et al. in the case of azuli-and benziporphyrinoids. 37 Interestingly, metal-mediated meso-extrusion has been primarily limited to porphycene. 38 Not surprisingly, meso-activation generally results in the formation of high-energy intermediates inducing structural modication (i.e., ring contraction) as a means to reach an energetic minimum. Owing to the complex architectures and difficulty in observing oen transient intermediates, mechanistic rationales for such transformations are rarely detailed. 18,23,25,36 Furthermore, the proposed mechanisms usually fail to include computational analyses as additional support. Here, we report the synthesis of a new hexaphyrin, pyrihexaphyrin (0.

Results and discussion
Pyrihexaphyrin (1) was designed to combine within one molecular framework key features of amethyrin 40 and dipyriamethyrin. 41 It was prepared in 86% yield via a triuoroacetic acid (TFA) catalyzed cyclization of 5,5 0 -(pyridine-2,6-diyl) bis(pyrrole-2-carbaldehyde) (2) 42 and terpyrrole (3) 43 (Scheme 2). Proton NMR spectroscopic analyses of pyrihexaphyrin 1 in CDCl 3 revealed features consistent with a non-aromatic porphyrinoid core. In particular, resonances attributed to the pyridine CH protons and pyrrole NH protons were not shied (ESI S3 †). The UV-vis absorption spectrum of 1 recorded in CHCl 3 is characterized by a Soret-like band at l max ¼ 452 nm (3 ¼ 43 000 M À1 cm À1 ) and two smaller peaks at l ¼ 372 nm (3 ¼ 17 000 M À1 cm À1 ) and l ¼ 278 nm (3 ¼ 14 000 M À1 cm À1 ) ( Fig. 2). A broad shoulder extending from l ¼ 600 to 850 nm is also seen. A cyclic voltammogram (CV) of 1 recorded in acetonitrile ([1] ¼ 1 mM) revealed a quasi-reversible oxidation feature at 27 mV relative to Fc/Fc + and two quasi-reversible reduction waves at À1267 mV and À1992 mV. An irreversible reduction was also observed at À1600 mV. An irreversible oxidation was observed on the return sweep at À518 mV and two irreversible oxidation peaks were observed above 250 mV. These peaks are attributed to reversible two electron oxidation and reduction processes involving the pyrihexaphyrin ring with irreversible events being observed at higher redox potentials. 44,45 Initial efforts at probing the coordination chemistry with transition metal and lanthanide cation salts returned mixtures of starting material and putative incorporation of methoxide within the meso-position with and without metal insertion, as inferred from mass spectrometric analyses (ESI S6-S10 †). Cation sources tested in this regard included AgOAc, Cu(OAc) 2 , Co(OAc) 2 , Fe(OAC) 2 , In(OAc) 3 , ZrCl 4 , Ni(OAc) 2 , Gd(OAc) 3 , and VO(acac) 2 .
Both amethyrin and dipyriamethyrin are known to stabilize complexes with certain actinyl ions. 40,41 This led us to explore whether a uranyl(VI) (UO 2 2+ ) complex could be stabilized using 1. However, in contrast with what was previously seen, a ringcontracted product was obtained. Specically, reaction of compound 1 with three equivalents of uranyl silylamide [UO 2 [-N(SiMe 3 ) 2 ] 2 ] 46 in tetrahydrofuran followed by purication over basic aluminum oxide § gave the 22 p-electron aromatic contracted pyrihexaphyrin (0.0.0.0.1.0)-uranyl complex (4)  ion is also expected to provide stabilization for the high-lying HOMO of a 22 p-electron Hückel-type aromatic core. Proton NMR spectroscopic analyses revealed that 4 possessed relatively low symmetry, as inferred from the large number of observable signals. Downeld shis in the proton resonances corresponding to the pyridine CH peaks and meso-CH peak were also seen. These shis mirror what had been observed in the case of napthoisoamethyrin, 47 isoamethyrin, 48 and amethyrin 40 upon uranyl coordination, ndings that were attributed to formation of a globally aromatic core. 49 UV-vis spectroscopic analyses revealed marked differences in comparison to previous hexaphyrin systems, as well as to the parent ligand 1. In particular, a relatively weak Soret-like band was observed at l max ¼ 549 nm (3 ¼ 18 400 M À1 cm À1 ), along with features at l ¼ 365 nm (3 ¼ 13 300 M À1 cm À1 ), l ¼ 734 nm (3 ¼ 4800 M À1 cm À1 ), and l ¼ 1003 nm (3 ¼ 9300 M À1 cm À1 ) (Fig. 2). CV studies of complex 4 (1 mM in acetonitrile) revealed two quasi-reversible peaks at À916 mV and À1270 mV vs Fc/Fc + , respectively. A slight shoulder preceding the reduction event at À1270 mV was observed at À960 mV. Two quasi-reversible oxidation events were observed at 236 mV and 445 mV (Fig. 2). These complex redox features suggest instability of the radical intermediates with concomitant decomposition via chemical reaction. A separate mechanism wherein electronic communication between the uranyl(VI) and the porphyrinoid ligand stabilizes intermediate radical species with distinct redox events might also be operative.
Single crystals suitable for X-ray diffraction analysis of 1 and 4 were grown via slow evaporation of a CH 2 Cl 2 : hexanes mixture (1 : 1, v/v). As shown in Fig. 3, the metal-free pyrihexaphyrin (1) adopts a twisted conformation wherein the central pyridine (N1) and pyrrole (N4) point in toward the concave face. The distortion largely involves torsion between the central heterocycles and dipyrromethene subunits. The cavity size, as measured from the in-plane dipyrromethene subunits, was found to be 5.846Å (N3 to N6). On this basis, the cavity size of 1 is similar to that of dipyriamethyrin, but smaller than amethyrin, for which opposing N-N distances of 5.858Å and 6.055Å were found, respectively.
As expected for an aromatic system, upon uranyl cation complexation and contraction, a structure (4) with greater overall planarity was obtained (Fig. 3). Complex 4 displays an atypical asymmetric coordination environment characterized by a distorted hexagonal bipyramidal geometry. Relevant bond angles were: 59.32 (N1 to N2), 58.26 (N2 to N3), 58.74 (N3 to N4), 59.28 (N4 to N5), 67.18 (N5 to N6), and 59.60 (N6 to N1). Uranyl-to-nitrogen bond distances were: 2.532 (6)Å (N4), 2.557 In an effort to understand the unique reactivity of 1, density functional theory (DFT) calculations were carried out using the Gaussian 16 package. 50 Geometric relaxations were performed using the X-ray crystal structural parameters so as to obtain energy minimized structures (Fig. S1 †) and simulated spectra (Fig. S2 †). Concordance with the experimental data was seen in both cases.  The aromatic nature of 1 was probed using nucleus independent chemical shis (NICS) 51 and anisotropy induced current density (ACID) 52 plots. As expected, 1 gave an NICS value of 1.119, indicative of a non-aromatic species, while the ACID plot displayed a node between the meso-bridge and adjacent pyrroles, indicating weak conjugation (Fig. S3 †). An electrostatic potential map showed neutral to high levels of electron density throughout the macrocycle (Fig. S4 †). In contrast, the ACID plot for the uranyl complex 4 revealed a clockwise current characteristic of a diatropic p-system (Fig. S5 †). This was taken as further evidence that complex 4 is best considered as being an aromatic species rather than one with a more localized conjugation (e.g., 4 0 in Scheme 4).k A proposed mechanism for the metallation-contraction involved in the conversion of 1 to 4 is shown in Scheme 4. Briey, pyrihexaphyrin is expected to undergo deprotonationmediated metal insertion with concomitant oxidation to give the cationic uranyl(VI) complex A. Formation of A is postulated to proceed via an intramolecular uranyl(VI) [(L*U(IV)O 2 ) + ] facilitated ring oxidation to yield water and a uranium (IV) species 5 that is re-oxidized to the uranyl(VI) complex A upon exposure to air. 30,53 However, the alternative formation of a ligand-based radical-U(V) intermediate cannot be excluded. Bart, Schelter, and co-workers have recently reported the ability of redox-active iminoquinone ligands to facilitate oxo-activation and reduction of U(VI) to U(IV). 54 Furthermore, in the presence of a reductant and proton source, the reduction of U(VI)O 2 2+ under anaerobic conditions to yield U(VI) and water can occur. 54,55 In loose analogy to the ring-contraction central to the biosynthesis of vitamin B 12 , the activated metallo-expanded porphyrin A is expected to facilitate nucleophilic addition of a hydroxide anion into the meso-position to give dearomatized intermediate B. 56 Subsequent pyrrole a-addition into the uranylactivated C]N bond, followed by rearrangement of the 1,2donor-acceptor cyclopropanolate (C), would yield the exo-carbaldehyde D. 57 The porphyrinoid ring in conjunction with inplane uranyl(VI) center are expected to act as an electron sink and provide resonance stabilization to this intermediate, as illustrated in D 0 . A nal sequence of base-mediated fragmentation, 56b,58 proceeding via intermediate E and resonance stabilized intermediates F or F 0 with the uranyl(V) center acting as an electron sink with attendant delocalization across the porphyrinoid core, followed by aerobic oxidation would give the aromatic product 4.
An alternative mechanism may also be operative wherein hydroperoxide, present from the reduction of molecular oxygen and deprotonation by basic aluminum oxide, adds into the meso-position to give a hydroperoxide dearomatized intermediate. 56 Subsequent rearrangement of the 1,2-donor-acceptor peroxycyclopropane with attendant cleavage of the O-O peroxide bond would again yield an exo-carbaldehyde on an acarbon of the bipyrrole subunit. 57 A nal sequence of basemediated fragmentation, followed by oxidation would give the aromatic ring-contracted product 4 (Scheme S1 †). Support for the initial step of this proposed mechanism came from 1 H NMR analysis of intermediate 5 (Fig. S6 †), as well as low and high-resolution mass spectrometric analyses and the observation of peaks consistent with intermediate A (Fig. S7 & S8 †).** In particular, the crude reaction mixture, ltered through Celite and dried under reduced pressure, yielded a proton NMR spectrum devoid of proton resonances with a signals attributed to water, THF, hexanes, NaHMDS, HN(SiMe 3 ) 2 , and CHCl 3 . While not denitive proof, these observations are consistent with the presence of a U(IV)-pyrihexaphyrin complex produced via reduction of U(VI)O 2 2+ with the lack of resonances attributed to the through-contact or -space transfer of spin density from the actinide ion to the porphyrinoid ligand. 59 An alternative formulation wherein the electrons are delocalized across a porphyrinoid-U(V) intermediate is also possible. † † The same solid was also utilized immediately for mass spectrometric analyses as a methanolic solution. In our hands, the use of non-aqueous uranyl silylamide Computational analysis via DFT calculations revealed an electrostatic potential map for A characterized by low levels of electron density throughout the macrocycle (Fig. S9 †). An ACID plot of A proved consistent what would be expected for a nonaromatic species with a non-planar geometry (Fig. S9 †). Also of note is that a stable porphycene-based ruthenium complex and porphycene-free base analogous to intermediate D have been isolated aer purication over basic aluminum oxide or in the presence of base, respectively. The resultant exo-carbaldehyde porphycenes displayed aromatic features and thus had no thermodynamic driving force to excise the pendant aldehyde. 38a,c Furthermore, uranyl (UO 2 2+ )-mediated oxidation to furnish globally aromatic expanded porphyrins has been observed with amethyrin, 40 naphthoisoamethyrin, 46 isoamethyrin, 47 cyclo [6]pyrrole, 60 and cyclo [1]furan [1]pyridine [4] pyrrole. 61, ‡ ‡ However, no intermediate species or postulated mechanisms have been reported for any of these systems.

Conclusions
In conclusion, a new expanded porphyrin, pyrihexaphyrin (0.1.0.0.1.0) (1) has been prepared. Treatment of 1 with nonaqueous uranyl silylamide under anaerobic conditions, followed by purication on basic aluminum oxide exposed to air, yielded the ring contracted pyrihexaphyrin (0.0.0.0.1.0)-uranyl complex (4) with a 22 p-electron Hückel-type aromatic core. A postulated mechanism proceeding via a putative U(IV) intermediate followed by basic aluminum oxide mediated dearomatization-ring contraction is supported by proton NMR and MS spectroscopic analyses as well as DFT calculations. The present constructs thus provide insight into expanded porphyrinoid activation of the uranyl(VI) dication (UO 2 2+ ) while highlighting the unique reactivity of mixed porphyrinoid structures.

Conflicts of interest
There are no conicts to declare.