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. 2020 Jun 29;5(27):16951–16958. doi: 10.1021/acsomega.0c02290

Synthesis of IrIII Hydrido Complexes by Oxidative Addition of Halogenated Theophylline and Adenine Derivatives

Jonas Blumenberg 1, Florian Kampert 1, Alexander Hepp 1, F Ekkehardt Hahn 1,*
PMCID: PMC7366355  PMID: 32685865

Abstract

graphic file with name ao0c02290_0010.jpg

The IrIII hydrido complexes [1] and [2] have been synthesized by the regioselective oxidative addition of the N7–H bond of 8-halogenotheophyllines to [IrCl(coe)2]2 in the presence of PPh3. The use of dppf in this reaction yielded the bimetallic IrIII/FeII hydrido complexes [3] and [4]. X-ray diffraction studies confirmed that complexes [1]–[4] feature a theophyllinato ligand coordinated to the metal center in the rarely observed, chelating fashion via the N7 and O1 atoms. In addition, 8-bromoadenine reacts with [IrCl(coe)2]2 in the presence of PPh3 to form the IrIII hydrido complex [5] which features one anionic 8-bromoadeninato and one neutral 8-bromoadenine ligand linked by an intramolecular hydrogen bond. Complex [5] was characterized by high-resolution mass spectrometry and an X-ray diffraction analysis but could not be analyzed by nuclear magnetic resonance spectroscopy because of its low solubility.

Introduction

The oxidative addition of the C–X bond of halogenated azoles to low-valent transition metals, in the presence of a proton source, normally and regioselectively yields the complexes bearing C-metalated protic NHC ligands.1−3 Both C2-halogenated imidazoles4 and benzimidazoles5,6 have been used in this reaction with Ni0, Pd0, and Pt0 complexes. Depending on the starting material (unsubstituted 2-halogenoazoles or N-alkyl-2-halogenoazoles), complexes with diprotic NH, NH–NHC ligands5−6 or monoprotic NH, NR–NHC ligands7−9 (both of type I, Scheme 1, top) have been prepared.

Scheme 1. Oxidative Addition of Halogenated Azoles to M0 Transition-Metal Complexes.

Scheme 1

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Recent studies, however, revealed a different regioselectivity in the reaction of 2-chlorobenzimidazole or various 8-halogenotheophylline derivatives with [Ni0(cod)2]. In the presence of PEt3 and at low temperature, the NiII-hydrido-azolato complexes of type II were obtained with the C–halogeno bond still intact.10 This unusual N-metalation of halogenoazole derivatives was only observed in the oxidative addition to Ni0 at low temperature. If [Pd(PPh3)4] instead of Ni0 was used as a metal precursor, the oxidative addition of 8-halogenotheophyllines yielded the expected complexes of type III with a C-metalated azolato ligand, which upon addition of a proton acid react to give the complexes with the diprotic, unsymmetric NH, NH–NHC ligands IV.11

Based on these results, we became interested in a more detailed investigation of the oxidative addition of azole-type NHC precursors to metals in a higher oxidation state. The C2–X (X = halogen) oxidative addition of neutral halogenoazoles to IrI has not been investigated yet. However, the related oxidative addition of the C2–H bond of phosphine-tethered azoles to [RhCl(coe)2]2 has been described to yield NH, NR–NHC^phosphine chelate complexes of type V (Scheme 2, top).12 In addition, the C–Cl oxidative addition of various halogenothiazoles and oxazoles to iridium(I) is also known.13,14 Finally, the oxidative addition of the C2–H bond of donor-tethered azoles to IrIII complexes has been described (Scheme 2, bottom).15,16 Because of the alkylation of the azole ring nitrogen atom, these reactions lead to azole C-metalation.

Scheme 2. Reaction of Donor-Tethered Azoles with RhI and IrIII Complexes.

Scheme 2

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The reactions depicted in Scheme 2 proceed via coordination of the phosphine followed by oxidative addition of the C2–H bond of the azole to give a hydrido complex. This complex is not stable and reductively eliminates a proton which protonates the unsubstituted ring nitrogen atom of the azole.3,16 Thus, the oxidation state of the metal in complexes V and VI is not different from that of the starting materials.17

Here, we describe the oxidative addition of 8-halogenotheophyllines to iridium(I) complexes which proceeds regioselectively via N7-metalation of the five-membered diaminoheterocycle. The reaction product also features coordination of the C6-oxygen atom, thus leading to the rare coordination of theophylline as a bidentate chelate ligand. In addition, we describe the reaction of 8-bromoadenine with iridium(I) which also proceeds via an N–H oxidative addition to give a novel type of IrIII hydrido complex.

Results and Discussion

8-Halogenotheophyllines react with [IrCl(coe)2]2 in the presence of two equivalents PPh3 under substitution of the coe ligands and oxidative addition of the N7–H bond to form the IrIII hydrido complexes [1] and [2] in good yields of 82 or 72%, respectively. The complexes are soluble in polar aprotic organic solvents such as tetrahydrofuran (THF) and chloroform. They are stable against air and moisture for a short time but generally need to be stored under an inert gas atmosphere.

The formation of complexes [1] and [2] was initially indicated by high-resolution mass spectrometry–electrospray ionization (HRMS–ESI) spectrometry, showing the strongest peaks at m/z = 931.1697 (calcd for [[1] – Cl]+ 931.1704) and 1081.0645 (calcd for [[2] + Na]+ 1081.0646). The proton nuclear magnetic resonance (1H NMR) spectra of the complexes feature the characteristic resonances of the hydrido ligand at δ = −28.94 ppm for [1] and at δ = −28.83 ppm for [2]. These signals appear as doublets of doublets because of coupling to the two chemically different phosphorus atoms (Scheme 3). The resonance for the C6 carbon atom was detected in the 13C{1H} NMR spectra at δ = 162.2 ppm for [1] and at δ = 162.4 ppm for [2]. These resonances are shifted downfield by about 5 ppm relative to the C6=O resonance for free theophylline or of complexes bearing a monodentate N7-deprotonated theophylline ligand.18−21 We assume that the C6=O coordination to the iridium atom lowers the electron density at the oxygen atom, thereby causing the observed downfield shift of the C6 resonance. The 31P NMR spectra of [1] and [2] feature, as expected, each two resonances for the chemically different phosphorus atoms. These were recorded as dd or v-t (v-t = virtual triplet) resonances because of 2JPH and 2JPP coupling.

Scheme 3. N7–H Oxidative Addition of 8-Halogeno Theophyllines to [IrCl(coe)2]2/PPh3.

Scheme 3

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Single crystals of [1]·1.2toluene·0.3benzene were obtained by cooling a solution of [1] in toluene/benzene/CHCl3 to −30 °C. For a plot of the molecular structure of [1] and a listing of metric parameters, see the Supporting Information. Single crystals of [2]·2CHCl3 were grown by cooling a CHCl3/THF solution of [2] to −30 °C. The molecular structure analysis confirms the proposed chelating N7^O1 coordination mode of the theophyllinato ligand in [2] (Figure 1). This type of bidentate coordination has been observed occasionally for selected copper(II),20−23 platinum(II),24 and titanium(III)25 complexes. All of these complexes, however, have been obtained by N7-deprotonation of theophylline derivatives and subsequent reaction with a metal salt. Contrary to this, complexes [1] and [2] were obtained by theophylline N7–H oxidative addition to an iridium(I) complex.

Figure 1.

Figure 1

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Molecular structure of complex [2] in [2]·2CHCl3 (50% probability ellipsoids). Hydrogen atoms except for H1 have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Ir–Cl 2.3939(11), Ir–P1 2.2741(12), Ir–P2 2.2879(12), Ir–O1 2.373(3), Ir–N7 2.106(4), Ir–H1 1.43(8), N7–C8 1.334(6), N9–C8 1.364(6); Cl–Ir–P1 171.52(4), Cl–Ir–P2 86.73(4), Cl–Ir–O1 84.55(9), Cl–Ir–N7 83.93(11), Cl–Ir–H1 95(3), P1–Ir–P2 100.10(4), P1–Ir–O1 88.85(9), P1–Ir–N7 89.55(12), P1–Ir–H1 90(3), P2–Ir–O1 104.39(9), P2–Ir–N7 169.92(12), P2–Ir–H1 86(3), O1–Ir–N7 78.52(13), O1–Ir–H1 170(3), N7–Ir–H1 91(3), and N7–C8–N9 116.2(4).

The iridium atom in [2] is coordinated in a distorted octahedral fashion with the hydrido ligand located in the trans-position to the theophyllinato oxygen atom O1.26 As expected, the bite angle of the chelate ligand O1–Ir–N7 (78.52(13)°) deviates most strongly from 90°. The angle N7–C8–N9 within the azolato moiety of 116.2(4)° is substantially larger than that previously observed for C-metalated azolato rings.5−7,27,28 The C8–I bond, which was the expected site for an oxidative addition of the 8-iodotheophyllines, is still intact in [2]. Complex [1] adopts the same geometry as [2] and exhibits very similar metric parameters (see the Supporting Information).

Next, the reactivity of 8-halogenotheophyllines toward [IrCl(coe)2]2/dppf (dppf = 1,1′-bis(diphenylphosphino)-ferrocene) was investigated. This reaction also proceeds with the oxidative addition of the N7–H bond and the formation of the heterobimetallic FeII/IrIII hydrido complexes [3] and [4] in good yields of 83 and 76% (Scheme 4). The complexes are soluble in polar aprotic organic solvents and moderately stable against air and moisture. Storage for longer periods requires an inert gas atmosphere.

Scheme 4. N7–H Oxidative Addition of 8-Halogeno Theopyhllines to [IrCl(coe)2]2/dppf.

Scheme 4

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First indications for the formation of [3] and [4] came again from HRMS–ESI spectrometry showing the strongest peaks at m/z = 997.0664 (calcd for [[3] + H]+ 997.0659) and 1110.9833 (calcd for [[4] + Na]+ 1110.9840), respectively. The 1H NMR spectra feature the characteristic resonances for the hydrido ligands at δ = −28.70 ppm (dd, 2JHP = 21.1 Hz, 2JHP = 18.2 Hz) for [3] and at δ = −28.65 ppm (dd, 2JHP = 21.3 Hz, 2JHP = 18.2 Hz) for [4] with the characteristic coupling to the two chemically different phosphorous atoms. Coordination of the C6=O carbonyl group was assumed based on the downfield shift of about 5 ppm of the resonance for C6 in [3] (δ = 162.3 ppm) and [4] (δ = 162.5 ppm) compared to the C6 resonance in free theophyllines.18 Again, two phosphorus resonances were observed in the 31P NMR spectra as dd or v-t signals because of 2JPH and 2JPP coupling.

Single crystals of [3]·2THF and [4]·2THF were grown by cooling THF/Et2O solutions of [3] or [4] to −30 °C. Both compounds have been characterized by X-ray diffraction analyses. The molecular structures are very similar and only the molecular structure of [4] (Figure 2) will be discussed here (for a plot of the molecular structure of [3] and a listing of metric parameters, see the Supporting Information).

Figure 2.

Figure 2

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Molecular structure of complex [4] in [4]·2THF (50% probability ellipsoids). Hydrogen atoms except for H1 have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Ir–Cl 2.3892(6), Ir–P1 2.2699(6), Ir–P2 2.2588(6), Ir–O1 2.3961(15), Ir–N7 2.099(2), Ir–H1 1.40(2), N7–C8 1.340(3), N9–C8 1.364(3); Cl–Ir–P1 85.80(2), Cl–Ir–P2 174.78(2), Cl–Ir–O1 87.11(4), Cl–Ir–N7 84.41(5), Cl–Ir–H1 92.6(10), P1–Ir–P2 99.15(2), P1–Ir–O1 103.60(4), P1–Ir–N7 169.89(5), P1–Ir–H1 84.1(10), P2–Ir–O1 90.08(4), P2–Ir–N7 90.71(5), P2–Ir–H1 89.5(10), O1–Ir–N7 78.44(6), O1–Ir–H1 172.2(10), N7–Ir–H1 93.7(10), and N7–C8–N9 116.0(2).

Complex [4] features a distorted octahedral coordination geometry around the iridium atom. As was observed for complexes [1] and [2], the theophyllinato donor in [3] and [4] is also coordinated as a bidentate N7^O1 chelate ligand to the iridium atom. The C8–I bond remains intact during the N7–H oxidative addition.

Complexes [1]–[4] constitute additional examples for the preferred oxidative addition of 8-halogenotheophyllines to transition metals proceeding under the reaction of the N7–H bond while the C8–halogen bond remains intact. Previously, we reported the N7–H oxidative addition in the reaction of 8-halogenotheophyllines with [Ni(cod)2]/PEt3 (Scheme 1, middle)10 and the C8–halogen oxidative addition in the same reaction with [Pd(PPh3)4] (Scheme 1, bottom).11 These reactions are most likely thermodynamically controlled.10 The factors determining the outcome of the reaction of 8-halogenotheophyllines with IrI complexes are not yet clear, but it appears that the formation of the N7^O1 chelate rings favors the N7–H oxidative addition over the reaction at the C8–X bond. However, additional factors such as the strength of the C8–Ir versus the N7–Ir bond may also play an important role. For cases where the N7–H oxidative addition was previously observed (complex II in Scheme 1), a metal with a smaller radius than IrIII, namely, NiII, was used. This situation might prevent the formation of the N7^O chelate ligand in complexes of type II.

Finally, the oxidative addition of 8-bromoadenine to [IrCl(coe)2]2/PPh3 was studied. This reaction in THF at 60 °C and recrystallization from CHCl3 for 3 d at low temperature yielded the unusual iridium(III) hydrido complex [5]·4CHCl3 in 53% yield. Compound [5]·4CHCl3 proved very poorly soluble in all tested solvents and solvent mixtures containing THF, CHCl3, toluene, methanol, acetonitrile, dimethylformamide, dimethyl sulfoxide, and water. It already precipitated during the synthesis from a THF solution. Only a small amount of the complex could be redissolved in CHCl3 for recrystallization (Scheme 5). The metal center of [5] bears an adeninato and an adenine ligand both coordinating to the metal center via the N3 ring nitrogen atom.

Scheme 5. Oxidative Addition of 8-Bromoadenine to [IrCl(coe)2]2/PPh3.

Scheme 5

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The formation of [5] was indicated by HRMS–ESI spectrometry showing strong peaks at m/z = 753.1214 (calcd for [IrClH(PPh3)2]+ 753.1212) and 966.0857 (calcd for [[5] – C5H3N5Br]+ 966.0851). Because of its low solubility, NMR spectra of [5] could not be recorded. However, the isolated crystals of [5]·4CHCl3 were suitable for an X-ray diffraction analysis, and the molecular structure of complex [5], determined by X-ray diffraction, is depicted in Figure 3.

Figure 3.

Figure 3

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Molecular structure of complex [5] in [5]·4CHCl3 (50% probability ellipsoids). Hydrogen atoms except H1 and H9A have been omitted for clarity. Selected bond lengths (Å) and angles (deg): Ir–Cl 2.5062(6), Ir–P1 2.2840(7), Ir–P2 2.2975(7), Ir–N3A 2.146(2), Ir–N3B 2.138(2), Ir–H 1.22(3), N7A–C8A 1.308(4), N9A–C8A 1.368(4), N7B–C8B 1.325(3), N9B–C8B 1.353(3); Cl–Ir–P1 90.33(2), Cl–Ir–P2 99.78(2), Cl–Ir–N3A 90.25(6), Cl–Ir–N3B 91.43(6), Cl–Ir–H1 177.4(15), P1–Ir–P2 100.25(3), P1–Ir–N3A 172.96(6), P1–Ir–N3B 89.47(6), P1–Ir–H1 90.45(15), P2–Ir–N3A 86.56(6), P2–Ir–N3B 165.04(6), P2–Ir–H1 82.5(15), N3A–Ir–N3B 83.50(8), N3A–Ir–H1 88.8(15), N3B–Ir–H1 86.1(15), N7A–C8A–N9A 115.8(2), and N7B–C8B–N9B 119.4(2).

The iridium atom in [5] is coordinated in a distorted octahedral fashion. The two adenine-derived ligands coordinate via their N3 nitrogen atoms to IrIII together with two PPh3, a chlorido and a hydrido donor. One of the two adenine-derived ligands is the best described as a neutral 8-bromoadenin, whereas the other is an anionic 8-bromoadeninato donor. The two adenine units are connected via an intramolecular hydrogen bond (N9B···H9A 1.98(4) Å). The anionic adeninato ligand and the N9-protonated adenine ligand can be clearly distinguished based on the metric parameters observed in the respective five-membered diaminoheterocycles. In accordance with expectations, the C4B–N9B–C8B angle in the deprotonated adeninato ligand of 101.2(2)° is significantly smaller than the equivalent angle in the protonated adenine ligand (C4A–N9A–C8A, 104.9(2)°).

The ligand types identified in complex [5] enable the development of a proposal for its formation. In the absence of the complete set of spectroscopic data, due to poor solubility, this mechanistic proposal at this time is solely based on the observed experimental outcome.

Given the fact that [5] features a hydrido ligand and an IrIII center, an oxidative addition of the N9–H bond of an adenine molecule to iridium(I) must have occurred. This oxidative addition would yield intermediate A, as shown in Scheme 6. Orthometalation of one of the triphenylphosphine ligands29 could also lead to a hydrido complex but no indications for such a reaction have been found in complex [5].

Scheme 6. Proposal for the Formation of [5].

Scheme 6

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Next, a second, neutral adenine molecule can coordinate to the IrIII center, either via its N7 or N3 ring nitrogen atom. A chelating N7^NH2 coordination of the second adenine molecule is rather unlikely, as it would require two free coordination sites in A. Monodentate coordination of the second bromoadenine ligand via N7 is also less likely for steric reasons. Coordination of the second adenine molecule via the N3 nitrogen atom to give intermediate B is thus most likely. For the formation of the final reaction product [5], the initially N9-bound adeninato ligand has to rearrange from N9 to N3 bonding to allow for the formation of the observed intramolecular N9A–H9A···N9B hydrogen bond in [5].

Conclusions

The reaction of 8-halogenotheophyllines with [IrCl(coe)2]2 in the presence of phosphines (PPh3 or dppf) proceeds by a regioselective oxidative addition of the N7–H bond to yield the IrIII hydrido–theophyllinato complexes [1]–[4]. The known alternative oxidative addition of the C8–halogen bond has not been observed. In complexes [1]–[4], the theophyllinato ligand coordinates as a rarely observed bidentate N7^O1 chelate ligand. The chelating coordination of the N7^O1 donor might be the driving force for the preferred N7–H oxidative addition which would not be possible upon C8–halogen oxidative addition. Complex [5], involving at least one oxidative addition of the N9–H bond of adenine, has also been prepared. An intramolecular N9–H···N9 hydrogen bond appears to be the driving force for the formation of [5]. Further studies regarding the regioselectivity of the oxidative addition of theophyllines to transition metals are in progress.

Experimental Section

General Procedures

All manipulations were carried out under an argon atmosphere unless stated otherwise. 1H and 13C{1H} NMR spectra were measured on a Bruker AVANCE I 400, Bruker AVANCE III 400, or Bruker AVANCE Neo 500SB spectrometer. Chemical shifts (δ) are expressed in ppm relative to SiMe4 using the residual protonated solvent signal as an internal standard. For the assignments of the NMR resonances, see the numbering at the molecular plots. Coupling constants are expressed in Hz. Mass spectra were obtained with an Orbitrap LTQ XL spectrometer (Thermo Scientific). 8-Iodotheophylline30 and 8-bromoadenine31 were prepared as described in the literature.

Synthesis of [1]

graphic file with name ao0c02290_0011.jpgA solution of [IrCl(coe)2]2 (30 mg, 0.033 mmol) in THF (10 mL) was treated with PPh3 (35 mg, 0.132 mmol). The resulting mixture was stirred for 10 min at 25 °C. Over this period, the color of the solution changes from orange to orange-red. Subsequently, 8-chlorotheophylline (14 mg, 0.065 mmol) was added and the reaction mixture was heated to 60 °C for 16 h. Over this period, a slightly yellow-colored solution formed. The volume was reduced to about 0.5 mL under reduced pressure, and n-hexane (10 mL) was added which caused the formation of a precipitate. This solid was isolated by filtration, washed with n-hexane (3 × 10 mL) and Et2O (3 × 10 mL), and dried in vacuo. Complex [1] was isolated as a colorless solid. Yield: 51 mg (0.053 mmol, 82%). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.50 (m, 6H, Ph-bortho), 7.26 (m, 12H, Ph-aortho + Ph-apara + Ph-bpara), 7.16 (m, 6H, Ph-bmeta), 7.06 (m, 6H, Ph-ameta), 3.46 (s, 3H, H10), 3.33 (s, 3H, H11), −28.94 (dd, 2JHP = 21.3 Hz, 2JHP = 16.7 Hz, 1H, Ir–H). 13C{1H} NMR (101 MHz, CDCl3): δ (ppm) 162.2 (C6), 152.1 (C2), 148.7 (d, 4JCP = 3.8 Hz, C4) 2P, 143.8 (d, 3JCP = 3.6 Hz, C8) 2P, 134.7 (d, 2JCP = 9.6 Hz, Ph-bortho), 133.9 (d, 2JCP = 10.0 Hz, Ph-aortho), 131.5 (d, 1JCP = 60.0 Hz, Ph-bipso), 130.2 (d, 4JCP = 2.5 Hz, Ph-apara), 130.0 (d, 4JCP = 2.5 Hz, Ph-bpara), 129.5 (d, 1JCP = 59.0 Hz, Ph-aipso), 127.6 (d, 3JCP = 10.7 Hz, Ph-bmeta), 127.5 (d, 3JCP = 10.7 Hz, Ph-ameta), 120.0 (C5), 30.0 (C11), 27.6 (C10). 31P NMR (162 MHz, CDCl3): δ (ppm) 5.5 (v-t, 2JPH = 2JPP = 16.7 Hz, PPh3-a), −2.6 (dd, 2JPH = 21.3 Hz, 2JPP = 16.7 Hz, PPh3-b). HRMS (ESI, positive ions): m/z (%) 931.1697 (100, calcd for [[1] – Cl]+ 931.1704), 989.1288 (10, calcd for [[1] + Na]+ 989.1284).

Synthesis of [2]

graphic file with name ao0c02290_0012.jpgA solution of [IrCl(coe)2]2 (30 mg, 0.033 mmol) in THF (10 mL) was treated with PPh3 (35 mg, 0.132 mmol). The resulting solution was stirred for 10 min at 25 °C. Over this period, the color of the solution changes from orange to orange-red. Subsequently, 8-iodotheophylline (20 mg, 0.065 mmol) was added and the mixture was heated to 60 °C for 16 h. Over this period, a slightly yellow-colored solution formed. The volume was reduced to about 0.5 mL under reduced pressure, and n-hexane (10 mL) was added which caused the formation of a precipitate. This solid was isolated by filtration, washed with n-hexane (3 × 10 mL) and Et2O (3 × 10 mL), and dried in vacuo. Complex [2] was isolated as a colorless solid. Yield: 50 mg (0.047 mmol, 72%). 1H NMR (500 MHz, CDCl3): δ (ppm) 7.49 (m, 6H, Ph-bortho), 7.31 (m, 6H, Ph-aortho), 7.26 (m, 3H, Ph-bpara), 7.23 (m, 3H, Ph-apara), 7.17 (m, 6H, Ph-bmeta), 7.06 (m, 6H, Ph-ameta), 3.44 (s, 3H, H10), 3.34 (s, 3H, H11), −28.83 (dd, 2JHP = 21.7 Hz, 2JHP = 16.5 Hz, 1H, Ir–H). 13C{1H} NMR (126 MHz, CDCl3): δ (ppm) 162.4 (C6), 151.9 (C2), 150.1 (d, 4JCP = 3.8 Hz, C4) 2P, 134.7 (d, 2JCP = 9.6 Hz, Ph-bortho), 134.1 (d, 2JCP = 9.9 Hz, Ph-aortho), 131.6 (d, 1JCP = 59.7 Hz, Ph-bipso), 130.2 (d, 4JCP = 2.4 Hz, Ph-apara), 130.0 (d, 4JCP = 2.4 Hz, Ph-bpara), 129.5 (d, 1JCP = 59.0 Hz, Ph-aipso), 127.7 (d, 3JCP = 10.6 Hz, Ph-bmeta), 127.4 (d, 3JCP = 10.6 Hz, Ph-ameta), 122.4 (d, 3JCP = 0.9 Hz, C5) 2P, 103.9 (d, 3JCP = 3.9 Hz, C8) 2P, 30.1 (C11), 27.6 (C10). 31P NMR (202 MHz, CDCl3): δ (ppm) 5.4 (v-t, 2JPH = 2JPP = 16.5 Hz, PPh3-a), −2.0 (dd, 2JPH = 21.7 Hz, 2JPP = 16.5 Hz, PPh3-b). HRMS (ESI, positive ions): m/z (%) 1023.1070 (15, calcd for [[2] – Cl]+ 1023.1068), 1059.0828 (55, calcd for [[2] + H]+ 1059.0827), 1081.0645 (100, calcd for [[2] + Na]+ 1081.0646).

Synthesis of [3]

graphic file with name ao0c02290_0013.jpgA solution of [IrCl(coe)2]2 (30 mg, 0.033 mmol) and dppf (37 mg, 0.067 mmol) in THF (10 mL) was treated with 8-chlorotheophylline (14 mg, 0.065 mmol). The obtained suspension was heated to 60 °C for 16 h. Over this period, an orange-colored solution formed. The volume of this solution was reduced to about 1 mL under reduced pressure, and n-hexane (10 mL) was added. This led to precipitation of a solid which was isolated by filtration, washed with n-hexane (3 × 10 mL) and Et2O (3 × 10 mL), and dried in vacuo. Complex [3] was isolated as a yellow solid. Yield: 55 mg (0.055 mmol, 83%). 1H NMR (400 MHz, CDCl3): δ (ppm) 8.06 (m, 2H, Ph-bortho1), 7.99 (m, 2H, Ph-bortho2), 7.46 (m, 9H, Ph-aortho1 + Ph-apara1 + Ph-bmeta1 + Ph-bpara1 + Ph-bmeta2 + Ph-bpara2), 7.26 (m, 2H, Ph-ameta1), 7.17 (m, 3H, Ph-aortho2 + Ph-apara2), 7.02 (m, 2H, Ph-ameta2), 5.23 (s, 1H, Cp-aα), 4.59 (s, 1H, Cp-aβ), 4.43 (s, 2H, Cp-aα′ + Cp-aβ′), 4.16 (s, 1H, Cp-bβ), 4.15 (s, 1H, Cp-bβ′), 3.84 (s, 1H, Cp-bα′), 3.81 (s, 1H, Cp-bα), 3.45 (s, 3H, H10), 3.33 (s, 3H, H11), −28.70 (dd, 2JHP = 21.1 Hz, 2JHP = 18.2 Hz, 1H, Ir–H). 13C{1H} NMR (101 MHz, CDCl3): δ (ppm) 162.3 (d, 4JCP = 1.2 Hz, C6) 2P, 152.1 (C2), 148.6 (d, 4JCP = 3.9 Hz, C4) 2P, 144.1 (d, 3JCP = 3.7 Hz, C8) 2P, 134.6 (d, 2JCP = 10.3 Hz, Ph-bortho2), 134.5 (d, 2JCP = 11.0 Hz, Ph-bortho1), 134.4 (d, 1JCP = 65.8 Hz, Ph-bipso2), 134.1 (d, 2JCP = 11.0 Hz, Ph-aortho1), 134.1 (Ph-apara1), 132.9 (d, 2JCP = 10.0 Hz, Ph-aortho2), 131.4 (d, 1JCP = 58.4 Hz, Ph-bipso1), 131.3 (d, 1JCP = 58.4 Hz, Ph-aipso2), 131.0 (d, 1JCP = 64.0 Hz, Ph-aipso1), 130.5 (d, 4JCP = 2.3 Hz, Ph-bpara1), 130.5 (d, 4JCP = 2.3 Hz, Ph-bpara2), 129.8 (d, 4JCP = 3.0 Hz, Ph-apara2), 128.0 (d, 3JCP = 10.7 Hz, Ph-bmeta2), 127.9 (d, 3JCP = 10.9 Hz, Ph-ameta1), 127.7 (d, 3JCP = 11.0 Hz, Ph-bmeta1), 127.1 (d, 3JCP = 10.5 Hz, Ph-ameta2), 119.7 (d, 3JCP = 1.2 Hz, C5), 77.3 (dd, 1JCP = 64.5 Hz, 3JCP = 2.7 Hz, Cp-bipso), 75.6 (d, 2JCP = 12.6 Hz, Cp-aα + Cp-bα), 75.6 (d, 2JCP = 13.7 Hz, Cp-aα′), 75.0 (d, 3JCP = 8.5 Hz, Cp-aβ), 74.5 (d, 2JCP = 10.0 Hz, Cp-bα′), 73.5 (dd, 1JCP = 69.0 Hz, 3JCP = 1.6 Hz, Cp-aipso), 73.4 (d, 3JCP = 7.2 Hz, Cp-aβ′), 72.6 (d, 3JCP = 7.1 Hz, Cp-bβ′), 71.6 (d, 3JCP = 6.4 Hz, Cp-bβ), 30.0 (C11), 27.7 (C10). 31P NMR (162 MHz, CDCl3): δ (ppm) 5.9 (dd, 2JPP = 13.0 Hz, 2JPH = 21.1 Hz, PPh2-a), −6.9 (v-t, 2JPP = 2JPH = 18.2 Hz, PPh2-b). HRMS (ESI, positive ions): m/z (%) 961.0898 (5, calcd for [[3] – Cl]+ 961.0898), 997.0664 (10, calcd for [[3] + H]+ 997.0659), 1019.0481 (10, calcd for [[3] + Na]+ 1019.0478).

Synthesis of [4]

graphic file with name ao0c02290_0014.jpgA solution of [IrCl(coe)2]2 (30 mg, 0.033 mmol) and dppf (37 mg, 0.067 mmol) in THF (10 mL) was treated with 8-iodotheophylline (20 mg, 0.065 mmol). The obtained suspension was heated to 60 °C for 16 h. Over this period, an orange-colored solution formed. The volume of this solution was reduced to about 1 mL under reduced pressure, and n-hexane (10 mL) was added. This led to precipitation of a solid which was isolated by filtration, washed with n-hexane (3 × 10 mL) and Et2O (3 × 10 mL), and dried in vacuo. Complex [4] was isolated as a yellow solid. Yield: 54 mg (0.050 mmol, 76%). 1H NMR (500 MHz, CDCl3): δ (ppm) 8.05 (m, 2H, Ph-bortho1), 8.01 (m, 2H, Ph-bortho2), 7.53 (m, 2H, Ph-aortho1), 7.46 (m, 4H, Ph-bpara1 + Ph-bmeta2 + Ph-bpara2), 7.45 (m, 1H, Ph-apara1), 7.44 (m, 2H, Ph-bmeta1), 7.29 (m, 2H, Ph-ameta1), 7.16 (m, 2H, Ph-aortho2), 7.12 (m, 1H, Ph-apara), 6.98 (m, 2H, Ph-ameta2), 5.32 (s, 1H, Cp-aα), 4.61 (s, 1H, Cp-aβ), 4.42 (s, 1H, Cp-aβ′), 4.39 (s, 1H, Cp-aα′), 4.16 (s, 1H, Cp-bβ), 4.15 (s, 1H, Cp-bβ′), 3.86 (s, 1H, Cp-bα′), 3.75 (s, 1H, Cp-bα), 3.45 (s, 3H, H10), 3.33 (s, 3H, H11), −28.65 (dd, 2JHP = 21.3 Hz, 2JHP = 18.0 Hz, 1H, Ir–H). 13C{1H} NMR (126 MHz, CDCl3): δ (ppm) 162.5 (C6), 151.9 (C2), 149.9 (d, 4JCP = 3.9 Hz, C4) 2P, 134.7 (d, 2JCP = 9.6 Hz, Ph-bortho2), 134.7 (d, 1JCP = 46.0 Hz, Ph-bipso2), 134.5 (br, Ph-aortho1), 134.4 (d, 2JCP = 10.2 Hz, Ph-bortho1), 132.9 (br, Ph-aortho2), 131.5 (br, Ph-apara1), 131.5 (d, 1JCP = 58.4 Hz, Ph-aipso2), 131.3 (d, 1JCP = 58.0 Hz, Ph-bipso1), 130.5 (d, 1JCP = 63.7 Hz, Ph-aipso1), 130.5 (d, 4JCP = 2.3 Hz, Ph-bpara1), 130.4 (d, 4JCP = 2.3 Hz, Ph-bpara2), 129.6 (br, Ph-apara2), 128.0 (d, 3JCP = 10.4 Hz, Ph-bmeta2), 127.9 (d, 3JCP = 10.8 Hz, Ph-ameta1), 127.7 (d, 3JCP = 11.2 Hz, Ph-bmeta1), 126.9 (d, 3JCP = 10.3 Hz, Ph-ameta2), 122.1 (C5), 104.1 (d, 3JCP = 4.3 Hz, C8) 2P, 77.3 (dd, 1JCP = 64.5 Hz, 3JCP = 2.7 Hz, Cp-bipso), 75.7 (Cp-aα + Cp-bα), 75.6 (Cp-aα′), 75.0 (d, 3JCP = 9.0 Hz, Cp-aβ), 74.3 (d, 2JCP = 9.8 Hz, Cp-bα′), 73.5 (dd, 1JCP = 69.0 Hz, 3JCP = 1.6 Hz, Cp-aipso), 73.3 (d, 3JCP = 6.8 Hz, Cp-aβ′), 72.7 (d, 3JCP = 7.1 Hz, Cp-bβ′), 71.4 (d, 3JCP = 6.4 Hz, Cp-bβ), 30.1 (C11), 27.6 (C10). 31P NMR (202 MHz, CDCl3): δ (ppm) 6.1 (dd, 2JPP = 12.7 Hz, 2JPH = 18.0 Hz, PPh2-a), −6.6 (br, PPh2-b). HRMS (ESI, positive ions): m/z (%) 1053.0260 (30, calcd for [[4] – Cl]+ 1053.0262), 1089.0017 (75, calcd for [[4] + H]+ 1089.0021), 1110.9833 (100, calcd for [[4] + Na]+ 1110.9840).

Synthesis of [5]

graphic file with name ao0c02290_0015.jpgA solution of [IrCl(coe)2]2 (30 mg, 0.033 mmol) and PPh3 (35 mg, 0.132 mmol) in THF (10 mL) was treated with 8-bromoadenine (28 mg, 0.131 mmol). The mixture was heated to 60 °C for 16 h. Over this period, a solid formed in the reaction mixture. Subsequently, the solvent was removed under reduced pressure, and the residue was washed with n-hexane (2 × 10 mL) and Et2O (2 × 10 mL). The obtained solid was then dissolved in CHCl3 (about 10 mL) and the cloudy solution was filtered again. The solution was stored at 25 °C for 3 d. Over this period, yellow crystals of composition [5]·4CHCl3 precipitated. These were isolated by filtration and dried in vacuo. Yield: 58 mg (0.035 mmol of [5]·4CHCl3, 53%). HRMS (ESI, positive ions): m/z (%) 753.1214 (100, calcd for [IrClH(PPh3)2]+ 753.1212), 966.0857 (20, calcd for [[5] – C5H3N5Br]+ 966.0851).

X-ray Crystallography

X-ray diffraction data were collected with a Bruker AXS APEXII CCD diffractometer equipped with a microsource using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). Semiemperical multiscan absorption corrections were applied to all data sets.32,33 Structure solutions were found with SHELXT (intrinsic phasing)34 and were refined with SHELXL35 against |F2| of all data using first isotropic and later anisotropic thermal parameters for all nonhydrogen atoms. Hydrogen atoms were added to the structure models on calculated positions. Crystallographic data for all compounds are summarized in the Supporting Information.

Crystal Data for [1]·1.2C7H8·0.3C6H6

Single crystals of [1]·1.2C7H8·0.3C6H6 were grown by cooling a solution of [1] in CHCl3/toluene/benzene to −30 °C. Formula C53.2H48.8N4Cl2IrO2P2, M = 1101.20 g·mol–1, colorless plate, 0.24 × 0.24 × 0.04 mm3, a = 31.4221(9), b = 18.4724(5), c = 18.3313(6) Å, β = 96.8550(10)°, V = 10,564.2(5) Å3, ρcalc = 1.385 g·cm–3, μ = 2.731 mm–1, monoclinic, space group C2/c, Z = 8, empirical absorption correction (0.57 ≤ T ≤ 0.71), T = 100(2) K, ω and φ scans, 85,631 intensities collected (5.23 ≤ 2θ ≤ 55.42°), 12,313 unique intensities (Rint = 0.0393) and 10,710 observed intensities (I ≥ 2σ(I)), and refinement of 553 parameters against |F2| of all independent intensities with hydrogen atoms on calculated positions. R = 0.0356, Rw = 0.0985, Rall = 0.0431, and Rw,all = 0.1044. The asymmetric unit contains one molecule of [1], 1.2 molecules of toluene, and 0.3 molecules of benzene.

Crystal Data for [2]·2CHCl3

Single crystals of [2]·2CHCl3 were grown by vapor-cooling a solution of [2] in CHCl3/Et2O to −30 °C. Formula C45H39N4Cl7IIrO2P2, M = 1297.07 g·mol–1, colorless plate, 0.37 × 0.29 × 0.19 mm3, a = 13.6487(2), b = 19.0356(3), c = 18.3707(3) Å, β = 96.227(1)°, V = 4744.75(13) Å3, ρcalc = 1.816 g·cm–3, μ = 3.969 mm–1, monoclinic, space group P21/c, Z = 4, empirical absorption correction (0.54 ≤ T ≤ 0.75), T = 100(2) K, ω and φ scans, 68,983 intensities collected (3.68 ≤ 2θ ≤ 55.2°), 10,990 unique intensities (Rint = 0.0172) and 10,228 observed intensities (I ≥ 2σ(I)), and refinement of 566 parameters against |F2| of all independent intensities with hydrogen atoms on calculated positions. R = 0.0379, Rw = 0.1104, Rall = 0.0408, and Rw,all = 0.1132. The asymmetric unit contains one formula unit of complex [2] and 2 molecules of CHCl3.

Crystal Data for [3]·2THF

Single crystals of [3]·2THF were grown by cooling a solution of [3] in THF/Et2O to −30 °C. Formula C49H51N4Cl2FeIrO4P2, M = 1140.82 g·mol–1, orange plate, 0.31 × 0.08 × 0.02 mm3, a = 11.7350(3), b = 12.2363(3), c = 17.4937(5) Å, α = 104.650(2), β = 107.734(2), γ = 95.338(2), V = 2275.03(11) Å3, ρcalc = 1.665 g·cm–3, μ = 3.479 mm–1, triclinic, space group P1̅, Z = 2, empirical absorption correction (0.41 ≤ T ≤ 0.93), T = 100(2) K, ω and φ scans, 31,619 intensities collected (3.50 ≤ 2θ ≤ 55.96°), 10,922 unique intensities (Rint = 0.0508) and 9806 observed intensities (I ≥ 2σ(I)), and refinement of 574 parameters against |F2| of all independent intensities with hydrogen atoms on calculated positions. R = 0.0463, Rw = 0.1106, Rall = 0.0531, and Rw,all = 0.1134. The asymmetric unit contains one formula unit of complex [3] and 2 molecules of THF.

Crystal Data for [4]·2THF

Single crystals of [4]·2THF were grown by cooling a solution of [4] in THF/Et2O to −30 °C. Formula C49H51N4ClFeIIrO4P2, M = 1232.27 g·mol–1, yellow prism, 0.23 × 0.20 × 0.08 mm3, a = 14.2092(8), b = 11.5302(14), c = 28.4666(15) Å, β = 92.113(4)°, V = 4660.7(7) Å3, ρcalc = 1.756 g·cm–3, μ = 4.001 mm–1, monoclinic, space group P21/c, Z = 4, empirical absorption correction (0.51 ≤ T ≤ 0.75), T = 100(2) K, ω and φ scans, 86,361 intensities collected (3.81 ≤ 2θ ≤ 64.51°), 15,416 unique intensities (Rint = 0.0507) and 13,179 observed intensities (I ≥ 2σ(I)), and refinement of 574 parameters against |F2| of all independent intensities with hydrogen atoms on calculated positions. R = 0.0259, Rw = 0.0349, Rall = 0.0523, and Rw,all = 0.0551. The asymmetric unit contains one formula unit of complex [4] and 2 molecules of THF.

Crystal Data for [5]·4CHCl3

Single crystals of [5]·4CHCl3 were grown by storing a CHCl3 solution of [5] for 3 d at 25 °C. Formula C50H42N10Br2Cl13IrP2, M = 1657.74 g·mol–1, colorless block, 0.40 × 0.40 × 0.20 mm3, a = 10.4686(5), b = 18.0388(8), c = 31.6485(13) Å, β = 95.9080(10)°, V = 5944.8(5) Å3, ρcalc = 1.852 g·cm–3, μ = 4.275 mm–1, monoclinic, space group P21/n, Z = 4, empirical absorption correction (0.28 ≤ T ≤ 0.48), T = 100(2) K, ω and φ scans, 110,068 intensities collected (6.85 ≤ 2θ ≤ 66.85°), 22,578 unique intensities (Rint = 0.0653) and 17,522 observed intensities (I ≥ 2σ(I)), and refinement of 731 parameters against |F2| of all independent intensities with hydrogen atoms on calculated positions. R = 0.0383, Rw = 0.0674, Rall = 0.0640, and Rw,all = 0.0737. The asymmetric unit contains one formula unit of [5] and 4 molecules of CHCl3.

Acknowledgments

The authors gratefully acknowledge financial support from the Deutsche Forschungsgemeinschaft (SFB 858 and IRTG 2017).

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c02290.

  • NMR spectra, plots, and selected metric parameters for all new compounds (PDF)

  • Crystallographic data for [1]·1.2C7H8·0.3C6H6 (CIF)

  • Crystallographic data for [2]·2CHCl3 (CIF)

  • Crystallographic data for [3]·2THF (CIF)

  • Crystallographic data for [4]·2THF (CIF)

  • Crystallographic data for [5]·4CHCl3 (CIF)

Accession Codes

CCDC 1981100–1981104 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

The authors declare no competing financial interest.

Supplementary Material

ao0c02290_si_001.pdf (676.9KB, pdf)
ao0c02290_si_002.cif (2.6MB, cif)
ao0c02290_si_003.cif (1.9MB, cif)
ao0c02290_si_004.cif (977.3KB, cif)
ao0c02290_si_005.cif (2.6MB, cif)
ao0c02290_si_006.cif (3.3MB, cif)

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao0c02290_si_001.pdf (676.9KB, pdf)
ao0c02290_si_002.cif (2.6MB, cif)
ao0c02290_si_003.cif (1.9MB, cif)
ao0c02290_si_004.cif (977.3KB, cif)
ao0c02290_si_005.cif (2.6MB, cif)
ao0c02290_si_006.cif (3.3MB, cif)

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