Selective C8-Metalation of Purine Nucleosides via Oxidative Addition

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Selective C8-Metalation of Purine Nucleosides via Oxidative Addition Florian Kampert, Dirk Brackemeyer, Tristan Tsai Yuan Tan, and F. Ekkehardt Hahn* Institut für Anorganische und Analytische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstraße 28-30, 48149 Münster, Germany

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S Supporting Information *

ABSTRACT: 8-Bromo-2′-deoxy-3′,5′-di-O-acetylguanosine (1), 8-bromo-2′,3′,5′-tri-O-acetylguanosine (2), 8-bromo-2′-deoxy3′,5′-di-O-acetyladenosine (3), and 8-bromo-2′,3′,5′-tri-O-acetyladenosine (4) react with [Pd(PPh3)4] via a C8−Br oxidative addition to give the C8-palladated azolato complexes [5]−[8] featuring an unprotonated N7 ring nitrogen atom. The complexes feature diastereotopic trans-disposed triphenylphosphine ligands, which allowed the determination of 2JPP for complexes of the type trans-[PdL2(PPh3)2] (2JPP = 442 Hz for [7]). In addition, two complex molecules of [7] form a trans-Watson−Crick/Hoogsteen AA base pair in the solid state. N7-protonation of the guanosinederived complexes [5] and [6] with HBF4·Et2O and of adenosinederived complexes [7] and [8] using lutidinium triflate yields complexes [9]BF4 and [10]BF4 and complexes [11]OTf and [12]OTf bearing protic NH,NR-NHC ligands derived from guanosine and adenosine, respectively. rom humble beginnings, the field of bioorganometallic chemistry has developed rapidly over the last 20 years. Apart of its early focus on the determination of biological structure and function, it has later reached out into domains of catalysis, medicinal chemistry, and bioanalysis.1 One of the most fundamental achievements was the discovery of the cytostatic properties of cisplatin and related compounds and the development of anticancer drugs from these compounds.2 Significant interactions between metal atoms and nucleic acids, in both biological systems and artificial compounds, were observed in the search for anticancer agents. Meanwhile, the metal binding sites in purine nucleobases, the building blocks of RNA and DNA, have been well established and a large number of coordination compounds between metals and nucleobases have been reported.3 However, metal complexes of purine nucleobases exhibiting an endocyclic carbon atom bound to a metal atom are rare and seldom feature additional unblocked Werner-type coordination sites.4 For the preparation of such compounds, the purine derivative is normally deprotonated at an endocyclic carbon atom and the resulting carbanion is competing with the Lewis basic nitrogen atoms of the purine scaffold for binding to the added metal ion. Starting with a first report by Bergman and Ellman,5a a series of publications have described the C2-metalation of N-donortethered neutral azoles (imidazoles and benzimidazoles). It is believed that this reaction proceeds by an initial coordination of the donor D,6 followed by oxidative addition of the C2−H bond and reductive elimination of a proton from the metal center with protonation of the ring nitrogen atom (Scheme 1, top).5b,7b This type of reaction has been observed with

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© XXXX American Chemical Society

Scheme 1. Synthesis of Complexes with N,NR-, NH,NR-, and NH,NH-NHC Ligands via Oxidative Addition of C−H and C−X Bonds (D = Donor, X = Halogen)

complexes of Rh,5 Ir,6 Ru,7 and Os8 in low oxidation states to facilitate the oxidative addition. The use of donor-tethered azoles thus leads to complexes of type I bearing a CNHC^D chelate ligand featuring a protic NHC (pNHC)9 donor (Scheme 1, top). Received: September 18, 2018

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DOI: 10.1021/acs.organomet.8b00685 Organometallics XXXX, XXX, XXX−XXX

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[5]−[8] bearing an anionic, nucleoside-derived NHC (or azolato) ligand in yields of 66−80%. Formation of complexes [5]−[8] was initially indicated by HRMS-ESI spectrometry (positive ions), where the peaks of the highest intensity were found at m/z 1062.1227 (calcd for [5 + H]+ 1062.2225), m/z 1120.1281 (calcd for [6 + H]+ 1120.1281), m/z 1046.1267 (calcd for [7 + H]+ 1046.1276), and m/z 1104.1337 (calcd for [8 + H]+ 1104.1332), respectively. The 13C{1H} NMR spectra feature the resonances of the azolato carbon atom C8 for the guanosine-derived palladium complexes [5] at δ 149.8 ppm and for [6] at δ 150.3 ppm. These chemical shifts compare well to the equivalent resonance for related azolato complexes obtained from 8chlorocaffeine.12 The resonances of the C8 carbon atoms for the adenosine-derived palladium complexes [7] and [8] both appear at δ 159.3 ppm, about 9 ppm downfield in comparison to the guanosine-derived azolato complexes. Intuitively, one would expect the C8 resonances for the electron-poorer guanosine-derived diaminoheterocycles more downfield than those of the adenosine-derived ligands. However, the diaminoheterocycles in complexes [5]−[8] are best described as azolato ligands rather than N7-deprotonated NHCs and the effects caused by the unsubstitutued ring nitrogen atom are not yet well understood. Thus, various factors, recently discussed in a review,14 may be responsible for the differences in the 13C NMR chemical shifts of the C8 carbon atoms in complexes [5]−[8]. Azolato complexes of palladium(II) obtained by oxidative addition from 2-chloro-N-alkylbenzimidazoles have a tendency to form dinuclear species. These result from an attack of the unsubstituted ring nitrogen atom of one azolato ligand at the metal center of a second complex molecule with substitution of one phosphine ligand.10b This reaction is typical for the kinetically more labile palladium(II) complexes and is less common for the more substitution inert platinum(II) complexes. However, no such dinuclear complexes were observed during the preparation of [5]−[8], most likely due to the steric congestion at the metal centers in these complexes and the reduced electron density at the unsubstituted N7 ring nitrogen atom caused by the electron-withdrawing effect of the sugar attached to the N9 ring nitrogen atom. A detailed inspection of the 31P{1H} NMR spectrum of [7] shows two doublet resonances which exhibit an extreme roof effect with coupling constants of 2JPP = 442 Hz between the trans-coordinated phosphorus atoms (Figure 1; red and blue dots mark one doublet each). The restricted rotation about the Pd−C bond (see the molecular structure in Figure 2) and the presence of stereocenters in the sugar moiety result in two

Alternatively, 2-halogenoazoles also react under oxidative addition of the C2−X bond to low-valent transition metals with no need for an N-tethered donor. N-alkyl-2-halogenoazoles10 as well as unsubstituted 2-halogenoazoles11 can be used for the oxidative addition to complexes containing zerovalent group 10 transition metals. For the N-alkyl-2halogenobenzimidazole, the initial reaction product, the azolato complex10b II reacts with a proton acid to give complex III bearing a protic NH,NR-NHC ligand, while the reaction of unsubstituted 2-halogenobenzimidazole in the presence of NH4BF4 directly yields complex IV, bearing the protic NH,NH-NHC ligand (Scheme 1, center). Recently, both C−X12 and the C−H13 oxidative additions have been used for the C8-metalation of purine nucleobases. The oxidative addition of the respective C8−halogen bonds of 8-bromo-9-methyladenine and 8-chlorocaffeine to Pt0 led to the formation of the first PtII complexes containing an azolato ligand derived from a purine scaffold (Scheme 1, bottom; complex V obtained from 8-bromo-9-methyladenine). Both isolated complexes with an azolato (or anionic N,NRsubstituted NHC) ligand derived from purine bases could subsequently be converted into NHC complexes bearing protic NH,NR-NHC ligands (e.g., VI).12 Furthermore, a N9− phosphine tethered adenine derivative was shown to react with suitable transition-metal precursors to give IrIII and RuII complexes bearing an NH,NR-NHC^PR2 chelate ligand.13 Herein, we present the preparation of various C8brominated purine nucleosides (derived from guanosine and adenosine) and the site-selective C8-metalation of these derivatives by oxidative addition of the C8−Br bond to [Pd(PPh3)4]. The NHC ligand precursor 1 was prepared by C8bromination of 2′-deoxyguanosine with N-bromosuccinimide followed by O-acylation with acetic anhydride (Scheme 2; see Scheme 2. Synthesis of PdII Complexes [5]−[8] Bearing Azolato Ligands Derived from Guanosine and Adenosine

the Supporting Information for experimental details). Similarly, ligand precursor 2 was prepared by C8-bromination of guanosine with Br2/H2O followed by O-acylation. The NHC precursors 3 and 4 were obtained similarly to 1 and 2 by C8bromination and O-acylation of 2′-deoxyadenosine or adenosine, respectively (see the Supporting Information for experimental details). The NHC precursors 1−4 mimic the nucleosides guanosine and adenosine, while the O-acylation makes them soluble in aprotic solvents such as THF. They react with [Pd(PPh3)4] in tetrahydrofuran at 80 °C to give the palladium(II) complexes

Figure 1. 31P{1H} spectrum of [7] in DMSO-d6. B


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Organometallics

conformation, which might be enforced by the bulky triphenylphosphine ligands attached to the metal center. The glycosidic bond and the associated torsion angle are aligned in the anti conformation (χ = 92.0(5)°). The conformation of the adenosine-derived azolato ligand allows the formation of the rare trans-Watson−Crick/Hoogsteen AA base pairing observed in the solid state.15 (see Figure S1 in the Supporting Information). As was shown with azolato complexes obtained from the oxidative addition of the C2−X bond of 2-halogenoazoles10,11 and the C8−X bond of purines12 to low-valent transition-metal complexes, protonation of the unsubstituted ring nitrogen atom N7 in azolato complexes [5]−[8] is also possible, leading (depending on the acid used) to complexes [9]BF4, [10]BF4, [11]OTf, and [12]OTf (Scheme 3). While the N protonation Scheme 3. N7-Protonation of the PdII Complexes [9]BF4− [12]OTf

Figure 2. Molecular structure of complex [7] in [7]·3C2H6OS (50% probability ellipsoids). Only one of the two essentially identical molecules in the unit cell is depicted, and hydrogen atoms have been omitted for clarity. Selected bond lengths (Å) and bond angles (deg) for [7]: Pd−Br 2.5103(5), Pd−P1 2.3186(12), Pd−P2 2.3304(13), Pd−C8 1.986(4), N7−C8 1.322(6), N9−C8 1.405(6); Br−Pd−P1 90.75(3), Br−Pd−P2 90.85(3), Br−Pd−C8 177.03(13), P1−Pd−P2 176.42(5), P1−Pd−C8 87.57(13), P2−Pd−C8 90.70(13), N7−C8− N9 112.3(4), C8−N7−C5 104.4(4), C8−N9−C4 106.2(4).

chemically nonequivalent phosphorus atoms in trans positions at the palladium center. To our knowledge, this is the first example of a palladium(II) complex bearing two diastereotopic triphenylphosphine ligands in trans coordination. This allows for the first time the determination of the 2JPP coupling constant in a trans-diphosphine palladium(II) complex (2JPP = 442 Hz). An AB spin system was also observed for the phosphorus atoms in complexes [5], [6], and [8]−[12] (see the Supporting Information), but the respective coupling constants could not always be determined, possibly due to an even more extreme roof effect. Single crystals of [7]·3DMSO were obtained by cooling of a concentrated DMSO solution of [7]. The X-ray diffraction analysis with these crystals revealed that the compound crystallizes, as expected for a chiral molecule, in an acentric space group (triclinic P1). Two essentially identical formula units reside in the unit cell. One of these is shown in Figure 2. The palladium atom in [7] is coordinated in a slightly distorted square planar fashion (sum of the four cis-L−M−L′ angles 359.9(4)°). The plane of the adenine ligand is oriented perpendicular to the coordination plane of the metal atom, as has been observed in related mononuclear PdII and PtII complexes.10−12 The N7−C8−N9 angle of 112.3(4)° in [7] is larger than the N−CNHC−N angle in benzimidazolin-2ylidene complexes (∼106°)9,10b but similar to the equivalent angles reported for the (azolato) N,NR-NHCs in V (111.7(2)°)12 and II (111.4(2)10b (see Scheme 1). In accord with previous observations,10b,12 the endocyclic C−N−C angle in the five-membered diazaheterocycle is small for the unsubstituted ring nitrogen atom N7 (104.40(4)°) and larger for the alkylated ring nitrogen atom N9 (106.2(4)°). In addition, and in contrast with classical NR,NR-NHC ligands, the C8−N bond distances in [7] feature different lengths with the shorter value observed for the bond to the unsubstituted ring nitrogen atom (N7−C8 1.322(6) Å and N9−C8 1.405(6) Å). The sugar (3′,5′-diacetyl-1′,2′-dideoxy-β-D-ribofuranose) attached at the N9 nitrogen atom exhibits the C2′-endo

of C2-coordinated benzimidazolato ligands requires only the presence of a weak acid such as NH4BF4,10,11 a stronger acid such as HBF4 has to be used for the N7 protonation of the guanosine-derived azolato ligands in [5] and [6]. The N7protonation of [7] and [8] proceeds with the weaker acid lutidinium triflate. Complexes [9]BF4, [10]BF4, [11]OTf, and [12]OTf have been fully characterized by 1H, 13C{1H}, and 31P{1H} NMR spectroscopy. The 1H NMR spectra feature the characteristic broad singlet for the N7−H proton at about 13 ppm. In accord with previous observations,10b,12 the N7 protonation leads to a downfield shift of about 10 ppm of the resonances for the carbene carbon atom C8. Crystals of ([10]BF4)2·4.5DMF·Et2O and [12]OTf were analyzed by X-ray diffraction. In both cases the palladium atom is coordinated in an almost ideal square-planar fashion typical for d8-metal complexes (Figure 3). As was observed for [7], steric congestion forces the NHC plane in an orientation perpendicular to the palladium coordination plane. The C8− Pd bond length in complex [12]+ is unaffected by the protonation of N7 and is identical within experimental error to the Pd−C8 bond length in [7]. The N7−C8−N9 bond angles in [10]+ and [12]+ (107.2(5) and 106.9(2)°) fall in the range observed for protic benzimidazolin-2-ylidene ligands (106.7(2)°)10b and are much smaller than the equivalent angle in the azolato complex [7] (112.3(4)°). The metric parameters observed in cations [10]+ and [12]+ are thus very close to those for complexes of classical protic NH,NR-NHC ligands. The complex cations [10]+ and [12]+ also show a smaller torsion angle χ in comparison to the neutral complex [7] to accommodate a third acetate group and reduce steric C


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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.8b00685. Experimental details and NMR spectra for all compounds (PDF) Accession Codes

CCDC 1868116−1868118 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 [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

*E-mail for F.E.H.: [email protected]. ORCID

F. Ekkehardt Hahn: 0000-0002-2807-7232 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors gratefully acknowledge financial support from the Deutsche Forschungsgemeinschaft (SFB 858 and IRTG 2027).

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Figure 3. Molecular structures of complex cations [10] in ([10]BF4)2·4.5DMF·Et2O (top) and [12]+ in [12]OTf (bottom). Solvent molecules, counterions, and hydrogen atoms (except for NHs) have been omitted for clarity (50% probability ellipsoids). The phenyl rings of the triphenylphosphine ligands are shown in wireframe to achieve a better graphical visualization. Selected bond lengths (Å) and bond angles (deg) for [10]+: Pd−Br 2.4667(6), Pd−P1 2.3331(13), Pd−P2 2.3478(13), Pd−C8 1.972(5), N7−C8 1.331(7), N9−C8 1.386(7); Br−Pd−P1 91.76(4), Br−Pd−P2 92.08(4), Br−Pd−C8 172.58(16), P1−Pd−P2 170.23(5), P1−Pd− C8 88.41(15), P2−Pd−C8 88.94(15), N7−C8−N9 107.2(5), C8− N7−C5 109.8(4), C8−N9−C4 109.0(4). Selected bond lengths (Å) and bond angles (deg) for [12]+: Pd−Br 2.4502(3), Pd−P1 2.3379(7), Pd−P2 2.3300(7), Pd−C8 1.977(2), N7−C8 1.329(3), N9−C8 1.372(3); Br−Pd−P1 89.84(2), Br−Pd−P2 90.84(2), Br− Pd−C8 176.90(7), P1−Pd−P2 175.06(3), P1−Pd−C8 87.78(7), P2−Pd−C8 91.69(7), N7−C8−N9 106.9(2), C8−N7−C5 110.7(2), C8−N9−C4 109.2(2).

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REFERENCES

(1) (a) Jaouen, G.; Vessières, A.; Top, S. Metal Carbonyl Fragments as a New Class of Markers in Molecular Biology. J. Am. Chem. Soc. 1985, 107, 4778−4780. (b) Hillard, E. A.; Jaouen, G. Bioorganometallics: Future Trends in Drug Discovery, Analytical Chemistry, and Catalysis. Organometallics 2011, 30, 20−27. (c) Monney, A.; Albrecht, M. Transition metal bioconjugates with an organometallic link between the metal and the biomolecular scaffold. Coord. Chem. Rev. 2013, 257, 2420−2433. (d) Bioorganometallic Chemistry: Applications in Drug Discovery, Biocatalysis, and Imaging; Jaouen, G., Salmain, M., Eds.; Wiley-VCH: Weinheim, 2015. (2) (a) Clarke, M. F.; Zhu, F.; Frasca, D. R. Non-Platinum Chemotherapeutic Metallopharmaceuticals. Chem. Rev. 1999, 99, 2511−2533. (b) Wang, F.; Xu, J.; Habtemariam, A.; Bella, J.; Sadler, P. J. Competition between Glutathione and Guanine for a Ruthenium(II) Arene Anticancer Complex: Detection of a Sulfenato Intermediate. J. Am. Chem. Soc. 2005, 127, 17734−17743. (c) Zorbas, H.; Keppler, B. K. Cisplatin Damage: Are DNA Repair Proteins Saviors or Traitors in the Cell? ChemBioChem 2005, 6, 1157−1166. (d) Jung, Y.; Lippard, S. J. Direct Cellular Response to PlatinumInduced DNA Damage. Chem. Rev. 2007, 107, 1387−1407. (e) Reißner, T.; Schneider, S.; Schorr, S.; Carell, T. Crystal Structure of a Cisplatin-(1,3-GTG) Cross-Link within DNA Polymerase η. Angew. Chem., Int. Ed. 2010, 49, 3077−3080. (f) Sava, G.; Bergamo, A.; Dyson, P. J. Metal-based antitumor drugs in the post-genomic era: what comes next? Dalton Trans. 2011, 40, 9069−9075. (3) (a) Lippert, B. Multiplicity of metal ion binding patterns to nucleobases. Coord. Chem. Rev. 2000, 200−202, 487−516. (b) Lynam, J. M. Nucleobase-containing transition metal complexes as building blocks for biological markers and supramolecular structures. Dalton Trans. 2008, 4067−4078. (c) Galindo, M. A.; Houlton, A. Chelate-tethered nucleobases: New architectures and insights in metal ion-nucleobase chemistry. Inorg. Chim. Acta 2009, 362, 625−633. (d) Metal Complex-DNA Interactions; Hadjiliadis, N., Sletten, E., Eds.; Wiley-VCH: Weinheim, 2009. (e) Beobide, G.; Castillo, O.; Luque, A.; Pérez-Yáñez, S. Porous materials based on

repulsion. Both [10]+ and [12]+ exhibit the C2′-endo-sugar puckering with syn conformation around the glycosidic bond in the solid state. We have prepared the four modified RNA and DNA building blocks 1−4 which readily react with [Pd(PPh3)4] via oxidative addition of the C8−Br bond give neutral azolato complexes [5]−[8]. The azolato ligands in these complexes can be protonated at the N7 ring nitrogen atoms to give the complexes with protic NH,NR-NHC ligands derived from nucleosides. Since the metal complexes bearing C8-metalated nucleoside are easily prepared, chiral, and rather stable, they might find applications in asymmetric catalysis. Incorporation of the C8-halogenated nucleosides into RNA or DNA followed by C8-metalation appears possible and is the subject of current investigations. D


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Organometallics metal-nucleobase systerms sustained by coordination bonds and base pairing interactions. CrystEngComm 2015, 17, 3051−3059. (4) (a) Clarke, M. J.; Taube, H. Nitrogen-Bound and Carbon-Bound Xanthine Complexes of Ruthenium Amines. J. Am. Chem. Soc. 1975, 97, 1397−1403. (b) Beck, W.; Kottmair, N. Neue Ü bergangsmetallkomplexe mit Nuclein-Basen und Nucleosiden. Chem. Ber. 1976, 109, 970−993. (c) Johnson, A.; O’Connell, L. A.; Clarke, M. J. N7 and C8 coordinated purine complexes of [(NH3)5OsIII]. Crystal structures of 7-[9MeHyp(NH3)5Os]Cl3·H2O and 8-[1,3,7Me3Xan(NH3)5Os]Cl3·2H2O. Inorg. Chim. Acta 1993, 210, 151−157. (d) Gundersen, L.-L. Synthesis of a Binuclear 6-Purinylpalladiu(II) Complex and its Possible Role in Stille Couplings of 6-Chloropurines. Acta Chem. Scand. 1996, 50, 462−465. (e) Romerosa, A.; SuarezVarela, J.; Hidalgo, M. A.; Avila-Rosón, J. C.; Colacio, E. Synthesis and Molecular Structure of the First Metal Complex of an Analogue of Guanine with PdII-C(8) Binding. Inorg. Chem. 1997, 36, 3784− 3786. (f) Price, C.; Elsegood, M. R. J.; Clegg, W.; Rees, N. H.; Houlton, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 1762−1764. (g) Price, C.; Shipman, M. A.; Rees, N. H.; Elsegood, M. R. J.; Edwards, A. J.; Clegg, W.; Houlton, A. Macrochelation, Cyclometallation and G-Quartet Formation: N3- and C8-Bound PdII Complexes of Adenine and Guanine. Chem. - Eur. J. 2001, 7, 1194−1201. (h) Price, C.; Shipman, M. A.; Gummerson, S. L.; Houlton, A.; Clegg, W.; Elsegood, M. R. J. Ruthenium-carbon bond formation via cyclometallation of a nucleobase. J. Chem. Soc., Dalton Trans. 2001, 353−354. (i) Buncel, E.; Norris, A. R.; Racz, W. J.; Taylor, S. E. Metal Ion-C(8) Binding in Purine Nucleosides. Ready Formation of Carbon-bound Inosine and Guanosine Complexes of Methylmercury(II). J. Chem. Soc., Chem. Commun. 1979, 562−563. (5) (a) Tan, K. L.; Bergman, R. G.; Ellman, J. A. Intermediacy of an N-Heterocyclic Carbene Complex in the Catalytic C-H Activation of a Substituted Benzimidazole. J. Am. Chem. Soc. 2002, 124, 3202− 3203. (b) Naziruddin, R. A.; Hepp, A.; Pape, T.; Hahn, F. E. Synthesis of Rhodium(I) Complexes Bearing Bidentate NH,NH-NHC/ Phosphine Ligands. Organometallics 2011, 30, 5859−5866. (6) (a) Miranda-Soto, V.; Grotjahn, D. B.; DiPasquale, G. G.; Rheingold, A. L. T. Imidazolyl-2-yl Complexes of Cp*Ir as Bifunctional Ambident Reactants. J. Am. Chem. Soc. 2008, 130, 13200−13201. (b) Cepa, S.; Schulte to Brinke, C.; Roelfes, F.; Hahn, F. E. Hydrogen Activation by an Iridium(III) Complex Bearing a Bidentate Protic NH,NR-NHC^Phosphine Ligand. Organometallics 2015, 34, 5454−5460. (7) (a) Araki, K.; Kuwata, S.; Ikariya, T. Isolation and Interconversion of Protic N-Heterocyclic Carbene and Imidazolyl Complexes: Application to Catalytic Dehydrative Condensation of N(2-Pyridyl)benzimidazole and Allyl Alcohol. Organometallics 2008, 27, 2176−2178. (b) Hahn, F. E.; Naziruddin, A. R.; Hepp, A.; Pape, T. Synthesis, Characterization, and H-Bonding Abilities of Ruthenium(II) Complexes Bearing Bidentate NR,NH-Carbene/Phosphine Ligands. Organometallics 2010, 29, 5283−5288. (c) Miranda-Soto, V.; Grotjahn, D. B.; Cooksy, A. L.; Golen, J. A.; Moore, C. E.; Rheingold, A. L. A Labile and Catalytically Active Imidazol-2-yl Fragment. Angew. Chem., Int. Ed. 2011, 50, 631−635. (d) Toda, T.; Kuwata, S.; Ikariya, T. Unsymmetrical Pincer-Type Ruthenium Complexes Containing β-Protic Pyrazole and N-Heterocyclic Carbene Arms: Comparison of Brønsted Acidity of NH Groups in Second Coordination Sphere. Chem. - Eur. J. 2014, 20, 9539−9542. (e) Flowers, S. E.; Cossairt, B. Mono- and Dimetalation of a Tridentate Bisimidazol-Phosphine Ligand. Organometallics 2014, 33, 4341−4344. (8) Eguillor, B.; Esteruelas, M. A.; García-Raboso, J.; Oliván, M.; Oñate, E.; Pastor, I. M.; Peñafiel, I.; Yus, M. Osmium NHC Complexes from Alcohol-Functionalize Imidazoles and Imidazolium Salts. Organometallics 2011, 30, 1658−1667. (9) Kuwata, S.; Hahn, F. E. Complexes Bearing Protic NHeterocyclic Carbene Ligands. Chem. Rev. 2018, 118, 9642−9677. (10) (a) Kösterke, T.; Pape, T.; Hahn, F. E. Synthesis of NHC Complexes by Oxidative Addition of 2-Chloro-N-methylbenzimidazole. J. Am. Chem. Soc. 2011, 133, 2112−2115. (b) Kösterke, T.;

Kösters, J.; Würthwein, E.-U.; Mück-Lichtenfeld, C.; Schulte to Brinke, C.; Lahoz, F.; Hahn, F. E. Synthesis of Complexes Containing an Anionic NHC Ligand with an Unsubstituted Ring-Nitrogen Atom. Chem. - Eur. J. 2012, 18, 14594−14598. (c) Kösterke, T.; Pape, T.; Hahn, F. E. Synthesis of complexes bearing NH,NMe-substituted NHCs by oxidative addition of 2-halogenato-N-methylbenzimidazoles to Ni0. Chem. Commun. 2011, 47, 10773−10775. (11) (a) Das, R.; Daniliuc, C. G.; Hahn, F. E. Oxidative Addition of 2-Halogenoazoles - Direct Synthesis of Palladium(II) Complexes Bearing Protic NH,NH-Functionalized NHC Ligands. Angew. Chem., Int. Ed. 2014, 53, 1163−1166. (b) Das, R.; Hepp, A.; Daniliuc, C. G.; Hahn, F. E. Synthesis of Complexes with Protoic NH,NH-NHC Ligands via Oxidative Addition of 2-Halogenoazoles to Zero-Valent Transition Metals. Organometallics 2014, 33, 6975−6987. (12) Brackemeyer, D.; Hervé, A.; Schulte to Brinke, C.; Jahnke, M. C.; Hahn, F. E. A Versatile Methodology for the Regioselective C8Metalation of Purine Bases. J. Am. Chem. Soc. 2014, 136, 7841−7844. (13) Brackemeyer, D.; Schulte to Brinke, C.; Roelfes, F.; Hahn, F. E. Regioselective C8-metalation of N-phosphine tethered adenine derivatives via C8-H activation. Dalton Trans. 2017, 46, 4510−4513. (14) Huynh, H. V. Electronic Properties of N-Heterocyclic Carbenes and Their Empirical Determination. Chem. Rev. 2018, 118, 9457− 9492. (15) Leontis, N. B.; Stombaugh, J.; Westhof, E. The non-WatsonCrick base pairs and their associated isostericity matrices. Nucleic Acids Res. 2002, 30, 3497−3531.

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Selective C8-Metalation of Purine Nucleosides via Oxidative Addition

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