Communication pubs.acs.org/Organometallics
Sequential Nitrene Transfers to an Organometallic Half-Sandwich Iridium Complex Christopher R. Turlington, Peter S. White, Maurice Brookhart, and Joseph L. Templeton* W. R. Kenan Laboratory, Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, United States S Supporting Information *
ABSTRACT: Nitrene transfer to an iridium(Cp*) complex with a pyridyl-amide bidentate ligand drives an unexpected outer-sphere C−H activation and amide functionalization reaction mediated by this metal center. This is a significant departure from C−N bond-forming processes in mononuclear rhodium and iridium catalysts, which require C−H activation at the metal center prior to nitrene transfer and insertion (an inner-sphere C−H insertion pathway). The mechanism likely involves a high oxidation state iridium-imido reactive species capable of hydrogen atom abstraction and a radical-based rearrangement during the formation of the ultimate iridium product.
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Nitrene transfer to these Ir(Cp*) or Rh(Cp*) catalysts could yield the respective octahedral metal(V) nitrenoid complexes, but experimental evidence for high oxidation state intermediates is difficult to obtain from the catalytic reactions. Calculations support the involvement of reactive Ir(V) or Rh(V) nitrenoid species in their respective catalytic reactions,5 but this class of compounds is considered to be difficult to access due to electronic repulsion between a filled dπ orbital on the d4 metal and a filled p orbital on the nitrogen of the nitrene moiety.6 Less than a dozen iridium-imido compounds in lower oxidation states have been isolated, and they adopt geometries to minimize filled dπ and p orbital overlap.7 Only a few rhodium complexes in the +5 oxidation state are known, but these compounds do not contain multiple bonds to heteroatoms.8 In recent work on Rh(Cp*) and Ir(Cp*) complexes, we searched for reactive intermediates in stoichiometric oxygen atom transfer reactions; such reagents provide oxygen atoms that are isoelectronic to nitrene fragments.9,10 Stoichiometric oxidation reactions could be characterized in situ by NMR spectroscopy to garner details about the identity of the oxidized metal complexes. Transfer of a single nitrene equivalent to Ir(Cp*) and Rh(Cp*) complexes with a bidentate phenylpyridine ligand (phpy) and a labile, L-type ligand has been reported and resulted in nitrene insertion into the metal− carbon bond of coordinated phpy according to the inner-sphere C−H activation mechanism.5,11 In one example, insertion of a p-toluenesulfonamido (NTs) nitrene group into bidentate phpy of the complex [Ir(Cp*)(phpy)(NC-Me)]+ (1a) formed an iridium complex with a pyridyl-amide bidentate ligand (2a), which was verified by X-ray crystallography (Scheme 2).11 Rapid insertion precluded observation of potential intermediates, but
etal-catalyzed C−H amidation and amination reactions have value in constructing C−N bonds, which are prevalent in pharmaceuticals and natural products.1 Metal complexes of iron, manganese, palladium, and copper are all capable of catalyzing this oxidative coupling using nitrene precursors.2 Two reaction pathways are typically described for catalytic amidation and amination reactions.3 One pathway is an outer-sphere C−H insertion pathway, where oxidation transiently generates a metal-imido fragment that activates a C−H bond and results in insertion. The second pathway is an inner-sphere C−H activation pathway, where C−H activation occurs at the metal prior to nitrene transfer and insertion (Scheme 1). Scheme 1. C−H Insertion and C−H Activation Pathways for Metal-Catalyzed Amidation and Amination Reactions
Recently, mononuclear Cp* complexes of iridium and rhodium have been shown to catalyze a diverse array of amidation and amination reactions utilizing the inner-sphere C−H activation pathway (Cp* = η5-pentamethylcyclopentadienyl).4 These catalysts activate a C−H bond on substrates with a directing group and then forge the critical C−N bond after oxidation with alkyl or aryl azides. Loss of N2 drives C−N bond formation at the metal center. This strategy allows for catalytic amidation and amination of C−H bonds under mild conditions with innocuous byproduct generation. © XXXX American Chemical Society
Received: August 20, 2015
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DOI: 10.1021/acs.organomet.5b00717 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics
Two mechanisms are possible for outer-sphere C−H insertion reactions. Typically oxidation to a metal-imido fragment leads to hydrogen atom transfer from a substrate C−H bond to the nitrogen atom of the imido group.2,12 Radical rebound of the amine to the carbon-based radical sets the carbon−nitrogen bond, but a rearrangement would have to occur before this step for the formation of product 3. A mechanism less frequently observed is electrophilic aromatic substitution, in which the electrophilic nitrogen atom attacks the arene to form a carbon− nitrogen bond.13 A stabilized carbocation is generated, and proton loss is required to restore aromaticity. We favor a hydrogen atom transfer pathway because this could allow for a radical rearrangement on the aryl ring before the carbon− nitrogen bond forms. Electrophilic aromatic substitution seems less likely here because C−N bond formation would generate an incorrect aryl substitution pattern (the methyl and sulfonamide groups would be para). A plausible mechanism consistent with an outer-sphere C−H insertion is presented in Scheme 4. Nitrene transfer to 2b (after
Scheme 2. Stoichiometric Nitrene Transfer Reactions
what might be the outcome of nitrene transfer to the iridium complex with a pyridyl-amide bidentate ligand? This nitrogenbound bidentate ligand is more resistant to insertion reactions than phpy. A complex with this chelating ligand could potentially be oxidized to generate an intermediate that would persist long enough to be detected spectroscopically. Accordingly, we designed a reaction to test nitrene transfer to this iridium complex and discovered that, starting from the phenylpyridine complex, both an outer-sphere C−H insertion and an innersphere C−H activation reaction occur at the same iridium center. Stirring 2.5 equiv of the nitrene transfer reagent PhINTs (p-toluenesulfonyliminoiodobenzene) with the iridium complex [Ir(Cp*)(phpy)(NC−ArF)][B(ArF)4] (1b, Cp* = η5pentamethylcyclopentadienyl, phpy = κ2-phenylpyridine, NC−ArF = 3,5-bis(trifluoromethyl)benzonitrile, B(ArF)4 = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) for 3 days at room temperature yielded a single iridium product, 3 (Scheme 3).
Scheme 4. Plausible Mechanism for Formation of Product 3
Scheme 3. Synthesis of Compound 3
nitrile dissociation) likely generates a high oxidation state iridium complex that could be formulated as an Ir(V) nitrenoid or Ir(IV) imido diradical species (with radical character on the metal and on the nitrogen atom of the imido ligand). We prefer the Ir(IV) imido representation of this high-valent reactive species. This is consistent with the observation that electronic repulsion between a filled dπ orbital on the metal and filled p orbital of the nitrene would destabilize the metal−nitrogen double bond.14 Hydrogen atom abstraction by an Ir(IV) imido species would yield a paramagnetic Ir(IV) amido intermediate with an aromatic radical on the bidentate ligand. Sulfonyl groups often shift in a radical-based rearrangement.15 If the Ir(IV) amido intermediate is sufficiently long-lived, intramolecular radical rearrangement of the sulfonyl group to the meta position (relative to the methyl) would be possible. Importantly, a stable, paramagnetic Ir(Cp*) complex in the +4 oxidation state has recently been isolated and characterized, providing evidence that an Ir(IV) intermediate may be longlived.16 Radical rebound of the amide after sulfonyl rearrangement, followed by coordination of nitrile NC−ArF, would form 3. Sequential nitrene transfer to iridium complex 1b reveals that both an outer-sphere C−H insertion reaction and an inner-sphere C−H activation pathway are possible at the same iridium center. Intramolecular hydrogen atom abstraction likely occurs after oxidation of the iridium(III) species 2b. This discovery highlights alternate reaction pathways available during atom transfer oxidations and a possible deactivation mechanism of mononuclear Ir(Cp*) and Rh(Cp*) amination and amidation catalysts.
Roughly 1 equiv of the amine, H2NTs, was generated as a byproduct. Compound 2b was an undetected intermediate, because it formed cleanly in a 1:1 reaction of PhINTs and 1b. The surprising structure of complex 3 was elucidated by X-ray diffraction on a suitable crystal of the purified product (Supporting Information). Two equivalents of nitrene had been transferred and incorporated into the iridium starting compound 1b. The 1H and 13C NMR spectra of 3 confirmed this fact, as two distinct tosyl−CH3 resonances were identified in the spectra. Compound 3 was isolated in good yield (73%), and a sample of 3 was determined to be analytically pure by elemental analysis (Supporting Information). Nitrene transfer from PhINTs to the iridium complex 2b with a pyridyl-amide bidentate ligand initiates an unexpected series of transformations. The structure of the final iridium product 3 reveals that an outer-sphere C−H insertion reaction is accessible to form amidation products. This is a significant departure from the inner-sphere C−H activation reactions with mononuclear Ir(Cp*) and Rh(Cp*) catalysts. In addition, the sulfonamide moiety of the NTs group transferred to 1b is oriented meta to its respective methyl group after the second nitrene transfer and intramolecular C−H insertion reaction to form product 3, as opposed to the original para position. This change in regiochemistry suggests a radical rearrangement. B
DOI: 10.1021/acs.organomet.5b00717 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics
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(14) Hydrogen atom transfer from an alkyl ligand to an imido moiety has been reported in a similar nitrene transfer reaction to a copper(I) complex. A copper(II) imido complex was implicated as the likely reactive species. See: Bagchi, V.; Paraskevopoulou, P.; Das, P.; Chi, L.; Wang, Q.; Choudhury, A.; Mathieson, J. S.; Cronin, L.; Pardue, D. B.; Cundari, T. R.; Mitrikas, G.; Sanakis, Y.; Stavropoulos, P. J. Am. Chem. Soc. 2014, 136, 11362−11381. (15) Fox, J. M.; Morris, C. M.; Smyth, G. D.; Whitham, G. H. J. Chem. Soc., Perkin Trans. 1 1994, 6, 731−737. (16) Brewster, T. P.; Blakemore, J. D.; Schley, N. D.; Incarvito, C. D.; Hazari, N.; Brudvig, G. W.; Crabtree, R. H. Organometallics 2011, 30, 965−973.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.5b00717. Synthesis and characterization of iridium compound 3, including a crystallographic structure report and 1H and 13 C NMR spectra (PDF) Crystallographic data (CIF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS C.R.T. acknowledges support from the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1144081, and J.L.T. acknowledges support from the National Science Foundation under Grant No. CHE1058675.
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REFERENCES
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DOI: 10.1021/acs.organomet.5b00717 Organometallics XXXX, XXX, XXX−XXX
