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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Organometallics. Author manuscript; available in PMC 2010 April 6.
Published in final edited form as:
Organometallics. 2008 October 15; 27(22): 2744–5747.
doi:  10.1021/om8008712
PMCID: PMC2850069

Synthesis and Characterization of Fused-Ring Iridapyrroles


Treatment of aromatic nitriles with methyllithium produces N-lithiated imine reagents which, when reacted with (η2-cyclooctene)(Cl)Ir(PMe3)3, generate fused iridaazacycles via ortho-metallation. Mono-protonation of these iridaazacycles produces fused iridapyrrole derivatives, while di-protonation leads to several different pathways.

Over the past 25 years, a variety of aromatic metallacycles, i.e., aromatic ring systems containing a transition metal, have been synthesized, and their physical and chemical properties have been investigated.1 Our group has focused on synthesizing a family of iridium-containing aromatic ring systems, which currently includes iridabenzene, iridapyrylium, iridathiabenzene, iridafuran, and iridathiophene.2 All of these compounds have been produced by reacting "(Cl)Ir(PR3)3" with pentadienide or heteropentadienide reagents and using iridium-centered C–H bond activation to construct the six- or five-membered rings. Further manipulations then create the aromatic ring systems. Conspicuous from the above list of aromatic iridacycles are the nitrogen-containing systems, iridapyrrole3 and iridapyridine.4 To date, we have not succeeded in using azapentadienide reagents to construct these desired nitrogen-containing iridacycles.5 However, in this communication, we report a new approach to the synthesis of fused five-membered iridaazacycles and their conversion to fused iridapyrroles.

As shown in Scheme 1, treatment of benzonitrile with methyllithium in THF produces N-lithiated imine reagent A in situ.6 Further treatment with (η2-cyclooctene)(Cl)Ir(PMe3)3,7 followed by stirring for 30 minutes, produces the fused iridaazacycle, fac-1, in 90% isolated yield. The likely intermediate in this reaction is 16e species B which undergoes iridium-centered C–H bond activation at the ortho position of the phenyl ring. The fac geometry of product 1 is evident from the 31P{1H} NMR spectrum, which exhibits three distinct phosphorus signals for the three different phosphine ligands.8 In the 1H NMR, the four phenyl ring protons appear in the region δ 7.19–7.70, while the methyl resonates at δ 2.61. The metal-hydride is observed at δ -10.87 and exhibits a large coupling (137.0 Hz) due to the trans phosphine and small couplings (~20 Hz) due to the cis phosphines. In the 13C{1H} NMR, C1 resonates farthest downfield at δ 173.0, while the phenyl ring carbons appear in the region δ 120.7–158.0. Significantly, the signal for C3 (at δ 158.0) is a widely-spaced doublet (JC-P = 81.6 Hz), indicating that it is bound to iridium and strongly coupled to a trans phosphine. The methyl group resonates at δ 25.7.

Treatment of fac-1 with one equivalent of triflic acid in THF leads to protonation at the nitrogen center and production of the iridaisoindole, fac-2 (Scheme 1), in high yield. The NMR spectra of fac-2 are very similar to those of fac-1, except for the appearance of a new broad singlet at δ 9.70, attributable to the proton on nitrogen.9 This new signal shows a strong correlation with the ring methyl signal in the 1H COSY NMR spectrum. The detailed NMR spectra of fac-2 and the other compounds reported herein are available in Supporting Material.

The X-ray crystal structure of fac-2 has been obtained and is shown in Figure 1, while key bond distances are summarized in the figure caption. The 5,6 fused ring system is highly planar with a mean deviation of only 0.043 Å. Two reasonable resonance structures, I and II (Drawing 1), can be proposed for iridaisoindole 2. Both structures appear to contribute to the bonding, as evidenced by the partial delocalization of carbon-carbon bonding within the five-membered ring (C1–C2 = 1.457(4) Å; C2–C3 = 1.423(4) Å). However, the relatively short C1-N1 distance (1.280(4) Å), along with the relatively long C1–C2 distance, suggests that II is the more important of the two contributors, perhaps because it includes a fully conjugated (aromatic) six-membered ring. In this context, it is interesting to note that organic isoindoles readily undergo tautomerization to isoindolenine structures (Drawing 2), a process which restores full conjugation to the carbocyclic ring.10

Figure 1
Molecular structure of cation fac-2, using thermal ellipsoids at the 50% level. PMe3 methyl H's and triflate anion are not shown. Selected bond distances (Å): Ir1-P1, 2.3600(8); Ir1-P2, 2.3488(8); Ir1-P3, 2.2711(8); Ir1-N1, 2.096(3); Ir1-C3, 2.084(3); ...

As shown in Scheme 2, the same methodology can be used to generate related fused ring systems. Hence, treatment of 2-cyanopyridine with methyllithium, followed by (η2-cyclooctene)(Cl)Ir(PMe3)3,7 produces the 5,6 fused ring system, fac-3, via ortho C–H bond activation (Scheme 2, top). In the 1H NMR spectrum of fac-3, the three pyridyl protons resonate in the region of δ 6.86–8.57, while the ring methyl appears at δ 3.04. The metal-hydride resonates at δ -11.00 and, as expected, is split into an apparent doublet of triplets with one very large coupling (134.1 Hz), due to the trans phosphine, and two smaller couplings (21.0 Hz) due to the cis phosphines. In the 13C{1H} NMR spectrum, the signal for C1 is the most downfield at δ 175.4, while the pyridyl carbons resonate between δ 121.3 and δ 173.5. The signal for C3 is split into a widely-spaced doublet (JC-P = 86.0 Hz), indicating that it is bonded to iridium and located trans to a phosphine. Treatment of fac-3 with one equivalent of triflic acid leads to protonation at the nitrogen of the five-membered ring and production of the iridapyrrole derivative, fac-4. The NMR spectra of fac-4 strongly resemble those of fac-3, except for the addition of a broad NH resonance at δ 10.45. The structure of fac-4 has been confirmed by X-ray crystallography and is presented in Figure 2. The key bond distances, summarized in the figure caption, are very similar to those of fac-2, suggesting that resonance structure IV (Drawing 3) is the more important contributor to the bonding, probably because it includes a fully conjugated pyridine ring.

Figure 2
Molecular structure of cation fac-4, using thermal ellipsoids at the 50% level. PMe3 methyl H's and triflate anion are not shown. Selected bond distances (Å): Ir1-P1, 2.3590(7); Ir1-P2, 2.3453(7); Ir1-P3, 2.2670(7); Ir1-N1, 2.101(2); Ir1-C3, 2.083(2); ...

Using the same synthetic approach, treatment of 2-thiophenecarbonitrile with methyllithium, followed by (η2-cyclooctene)(Cl)Ir(PMe3)3,7 produces the 5,5 fused ring system, fac-5, via ortho C–H bond activation (Scheme 2, bottom). Treatment of fac-5 with one equivalent of triflic acid again leads to protonation at nitrogen and production of iridapyrrole derivative fac-6. As with iridapyrroles fac-2 and fac-4, one can draw two reasonable resonance structures for fac-6 (Drawing 4). However, in this case we predict that resonance structure V (Drawing 4) will be a more significant contributor than are I or III (vide supra) because the alternative structure, VI, has less to gain by fully conjugating the fused thiophene ring.11 This prediction is, in fact, supported by the X-ray crystal structure of fac-6, which has been obtained for the chloride salt, and is presented in Figure 3. As reported in the figure caption, the carbon-carbon bond lengths within the five-membered iridapyrrole ring of fac-6 are virtually identical (C1–C2 = 1.394(10) Å; C2–C3 = 1.396(11) Å), implying that resonance structures V and VI contribute equally to the bonding.

Figure 3
Molecular structure of cation fac-6, using thermal ellipsoids at the 50% level. PMe3 methyl H's, chloride anion, and toluene solvent molecule are not shown. Selected bond distances (Å): Ir1-P1, 2.333(2); Ir1-P2, 2.264(2); Ir1-P3, 2.350(2); Ir1-N1, ...

As shown in Scheme 3, each of the fused iridapyrrole complexes (fac-2, fac-4, and fac-6) is reactive toward a second equivalent of triflic acid. Interestingly, three different kinds of reaction products are observed. Treatment of fac-2 with triflic acid leads to formation of mer-7, a close analogue of fac-2, in which triflate has replaced hydride in the metal’s coordination sphere. A likely mechanism for this reaction involves protonation at iridium, followed by reductive elimination of H2 and triflate attack on the resulting 16e dicationic iridium center. The mer geometry of 7 is evident from the 31P{1H} NMR spectrum, which consists of just two signals, a doublet and a triplet in a characteristic 2:1 ratio. The 1H NMR spectrum of mer-7 is similar to that of fac-2 except for the absence of a metal-hydride signal. In the 13C{1H} NMR spectrum of mer-7, the signal for C3 is no longer coupled strongly to phosphorus, indicating that the triflate ligand (not PMe3) must reside trans to C3, as drawn in Scheme 3.

In contrast, treatment of fac-4 with a second equivalent of triflic acid results in simple protonation at the pyridine nitrogen and production of fac-8 (Scheme 3, middle). The 1H NMR spectrum of fac-8 is similar to that of fac-4, except for the appearance of a new broad NH signal at δ 14.53, which we have assigned to the pyridinium proton.12 The iridapyrrole proton appears at δ 11.17, slightly downfield from its position at δ 10.45 in precursor fac-4. The assignments of these protons are confirmed by the 1H COSY NMR spectrum; the signal at δ 14.53 correlates with the signal for pyridine ring proton H6, while the signal at δ 11.17 correlates with the ring methyl group.

Finally, treatment of fac-6 with a second equivalent of triflic acid results in skeletal rearrangement of the fused ring system and production of mer-9 (Scheme 3, bottom) in which sulfur is now bonded to iridium. Like the reaction of fac-2 described above, this reaction probably involves initial protonation at iridium. But instead of reductive elimination of H2, the thiophene ring (C3-H) eliminates, rotates, and then recoordinates through sulfur. The driving force for this rearrangement is probably relief of strain within the planar 5,5 fused ring system.

The structure of mer-9 has been confirmed by X-ray crystallography and is shown in Figure 4. The ring system is highly non-planar as a result of sulfur's rehybridization to sp3. The dihedral angle between the thiophene ring and the molecule's equatorial plane (Ir1/P1/S1/N1) is 40.9°. As expected, bonding within the ring system is rather localized (see caption to Figure 4). While the solid-state structure of mer-9 is highly non-planar, it displays mirror plane symmetry in solution by NMR. Hence, the two axial phosphines are equivalent by room temperature 31P{1H} NMR, implying that inversion at sulfur is facile.13 All other features of the NMR are fully consistent with the X-ray structure.

Figure 4
Molecular structure of dication mer-9, using thermal ellipsoids at the 50% level. PMe3 methyl H's and triflate anions are not shown. Selected bond distances (Å): Ir1-P1, 2.2995(4); Ir1-P2, 2.3452(4); Ir1-P3, 2.3471(4); Ir1-N1, 2.1018(11); Ir1-S1, ...

In this communication, we have introduced a new approach to the synthesis of five-membered iridaazacycles, using aromatic nitriles as the organic building blocks and CH bond activation to close the rings. Mono-protonation of these iridaazacycles leads to the production of novel iridapyrrole derivatives containing fused rings. Di-protonation, on the other hand, results in a variety of reaction pathways, only some of which leave the fused iridapyrrole framework intact.

Supplementary Material



P.P was supported by a Thai Government Scholarship. Washington University’s High-Resolution NMR Service Facility was funded in part by NIH Support Instrument Grants (RR-02004, RR-05018, and RR-07155). The regional X-ray Facility at the University of Missouri—St. Louis was funded in part by the National Science Foundation’s MRI Program (CHE-0420497).


Supporting Information Available: Detailed syntheses and characterization of compounds 1–9; structure determination summaries and listings of final atomic coordinates, thermal parameters, bond lengths, bond angles, and torsional angles for compounds fac-2 (triflate salt), fac-4 (triflate salt), fac-6 (chloride salt) , and mer-9 (triflate salt). This material is available free of charge via the Internet at

Contributor Information

John R. Bleeke, Department of Chemistry, Washington University, One Brookings Drive, St. Louis, Missouri 63130.

Phawit Putprasert, Department of Chemistry, Washington University, One Brookings Drive, St. Louis, Missouri 63130.

Todsapon Thananatthanachon, Department of Chemistry, Washington University, One Brookings Drive, St. Louis, Missouri 63130.

Nigam P. Rath, Department of Chemistry and Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis, Missouri 63121.

References and Notes

1. Recent reviews: a) Bleeke JR. Chem. Rev. 2001;101:1205–1227. [PubMed] b) He G, Xia H, Jia G. Chin. Sci. Bull. 2004;49:1543–1553. c) Wright LJ. J. Chem. Soc., Dalton Trans. 2006:1821–1827. d) Landorf CW, Haley MM. Angew. Chem. Int. Ed. 2006;45:3914–3936. [PubMed]
2. Bleeke JR. Acc. Chem. Res. 2007;40:1035–1047. [PubMed]
3. Several examples of iridapyrroles have been obtained using a 3+2 cycloaddition route: a) Alvarado Y, Daff PJ, Pérez PJ, Poveda ML, Sáchez-Delgado R, Carmona E. Organometallics. 1996;15:2192–2194. b) Alias FM, Daff PJ, Paneque M, Poveda M, Carmona E, Pérez PJ, Salazar V, Alvarado Y, Atencio R, Sánchez-Delgado R. Chem. Eur. J. 2002;8:5132–5146. [PubMed]
4. Iridapyridines are unknown. In fact, only one example of a metallapyridine, a tantalum derivative, has been reported: Weller KJ, Filippov I, Briggs PM, Wigley DE. Organometallics. 1998;17:322.
5. Reactions involving the bulky t-butylazapentadienide reagent result in the formation of allyl-iridium products: Bleeke JR, Luaders ST, Robinson KD. Organometallics. 1994;13:1592–1600.
6. Similar N-metallated imines have been produced by Erker: Erker G, Riedel M, Koch S, Jödicke T, Würthwein E-U. J. Org. Chem. 1995;60:5284–5290.
7. Herskovitz T, Guggenberger LJ. J. Am. Chem. Soc. 1976;98:1615–1616. In solution, this species dissociates cyclooctene to produce the reactive 16e "(Cl)Ir(PMe3)3".
8. Over time, fac-1 slowly converts to its mer isomer, mer-1, a reaction that can be easily monitored by 31P NMR spectroscopy. Slow fac to mer isomerizations are also observed for analogues 3 and 5 (vide infra).
9. For organic pyrroles, the NH signal is typically a broad resonance in the region δ7-δ12: Pouchert CJ, Behnke J. The Aldrich Library of 13C and 1H FT NMR Spectra: Aldrich Chemical Company. 1993;Vol. III:1–13.
10. a) Bird CW, Cheeseman GWH. In: Comprehensive Heterocyclic Chemistry. Katritzky AR, Rees CW, editors. Vol. 4. Oxford: Pergamon Press; 1984. pp. 1–38. b) Carey FA, Sundberg R. Advanced Organic Chemistry. 4th Edition. New York: Kluwer Academic/Plenum Publishers; 2000. pp. 540–543.
11. By a variety of criteria, thiophene is judged to be less aromatic than benzene or pyridine. See: Bird CW. Tetrahedron. 1996;52:9945–9952.
12. For organic pyridiniums, the NH signal is typically very broad and very downfield (often downfield from δ15): Pouchert CJ, Behnke J. The Aldrich Library of 13C and 1H FT NMR Spectra. Vol. III. Aldrich Chemical Company; p. 237.
13. While the activation energy is rather low for inversion about sulfonium sulfur, the planar intermediate would be stabilized by overlap of the filled sulfur pπ orbital with the ring's carbon π-system: Anderson KK. In: The Chemistry of the Sulphonium Group. Part 1. Stirling CJM, editor. Vol. 1981. England: Wiley: Chichester; 1981. pp. 229–266.