Published on Web 03/26/2005
Substrate Oxidation by Copper-Dioxygen Adducts: Mechanistic Considerations Jason Shearer,† Christiana Xin Zhang,† Lev N. Zakharov,‡ Arnold L. Rheingold,‡,¶ and Kenneth D. Karlin*,† Contribution from the Department of Chemistry, Johns Hopkins UniVersity, 3400 North Charles Street, Baltimore, Maryland 21218, and Department of Chemistry, UniVersity of Delaware, Newark, Delaware 19716 Received August 9, 2004; E-mail:
[email protected] Abstract: A series of copper-dioxygen adducts [{CuII(MePY2)R}2(O2)](B(C6F5)4)2 (1R), systematically varying in their electronic properties via ligand pyridyl donor substituents (R ) H, MeO, and Me2N), oxidize a variety of substrates with varying C-H or O-H bond dissociation enthalpies. Detailed mechanistic studies have been carried out, including investigation of 1R thermodynamic redox properties, 1R tetrahydrofuran (THF) and N,N′-dimethylaniline (DMA) oxidation kinetics (including analyses of substrate dicopper binding equilibria), and application of mechanistic probes (N-cyclopropyl-N-methylaniline (CMA) and (p-methoxyphenyl)-2,2-dimethylpropanol (MDP)), which can distinguish if proton-coupled electron-transfer (PCET) processes proceed through concerted electron-transfer proton-transfer (ETPT) or consecutive electrontransfer proton-transfer (ET/PT) pathways. The results are consistent with those of previous complementary studies; at low thermodynamic driving force for substrate oxidation, an ET/PT is operable, but once ET (i.e., substrate one-electron oxidation) becomes prohibitively uphill, the ETPT pathway occurs. Possible differences in coordination structures about 1Me2N/1MeO compared to those of 1H are also used to rationalize some of the observations.
Introduction
Copper-mediated oxidations are prominent in chemical and catalytic processes,1-9 while tyrosinase (Tyr),2,10 catechol oxidase (CO),2,11 dopamine-β-hydroxylase (DBH),3,12 and peptidylglycine R-hydroxylating monooxygenase (PHM)13-15 are widely studied copper-containing monooxygenases/oxidases. Tyr and CO are structurally related, containing a peroxo-bridged †
Johns Hopkins University. University of Delaware. ¶ Current address: Chemistry Department, University of California, San Diego, La Jolla, CA 92093. ‡
(1) Kitajima, N.; Moro-oka, Y. Chem. ReV. 1994, 94, 737-757. (2) Solomon, E. I.; Sundaram, U. M.; Machonkin, T. E. Chem. ReV. 1996, 96, 2563-2605. (3) Klinman, J. P. Chem. ReV. 1996, 96, 2541-2561. (4) Kopf, M.-A.; Karlin, K. D. In Biomimetic Oxidations; Meunier, B., Ed.; Imperial College Press: London, 2000; Chapter 7, pp 309-362. (5) Solomon, E. I.; Chen, P.; Metz, M.; Lee, S.-K.; Palmer, A. E. Angew. Chem., Int. Ed. 2001, 40, 4570-4590. (6) Que, L., Jr.; Tolman, W. B. Angew. Chem., Int. Ed. 2002, 41, 1114-1137. (7) Quant Hatcher, L.; Karlin, K. D. J. Biol. Inorg. Chem. 2004, 9, 669-683. (8) Mirica, L. M.; Ottenwaelder, X.; Stack, T. D. P. Chem. ReV. 2004, 104, 1013-1045. (9) Lewis, E. A.; Tolman, W. B. Chem. ReV. 2004, 104, 1047-1076. (10) Decker, H.; Dillinger, R.; Tuczek, F. Angew. Chem., Int. Ed. 2000, 39, 1591-1595. (11) Gerdemann, C.; Eicken, C.; Krebs, B. Acc. Chem. Res. 2002, 35, 183191. (12) Evans, J. P.; Ahn, K.; Klinman, J. P. J. Biol. Chem. 2003, 278, 4969149698. (13) Chen, P.; Bell, J.; Eipper, B. A.; Solomon, E. I. Biochemistry 2004, 43, 5735-5747. (14) (a) Chen, P.; Solomon, E. I. J. Am Chem. Soc. 2004, 126, 4991-5000. (b) Chen, P.; Solomon, E. I. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 1310513110. (15) Prigge, S. T.; Eipper, B.; Mains, R.; Amzel, L. M. Science 2004, 304, 864867. 10.1021/ja045191a CCC: $30.25 © 2005 American Chemical Society
magnetically coupled dinuclear CuII2 active site (Scheme 1).2,5,11 CO performs the catalytic conversion of ortho-catechols to ortho-quinones, while Tyr will both ortho-hydroxylate phenols and convert ortho-catechols to ortho-quinones (Scheme 1).7,16 Tyr facilitates phenol hydroxylations by first coordinating a phenol (or phenolate) to one of the copper centers followed by an electrophilic attack of the phenol ring by the peroxo moiety.2,10,17-19 In CO substrate dehydrogenation, concerted two-electron (two-proton) oxidation and radical-type protoncoupled electron-transfer (PCET) reaction mechanisms have been proposed.1,11,20 DBH and PHM proceed through initial hydrogen atom (H•) abstraction reactions, which have been proposed to occur from either a mononuclear CuII-O2-• or a CuII-OOH active-site oxidant.12-15 To aid in understanding the fundamental properties of the oxidative process in these metalloenzymes, as well as to potentially guide the design of oxidation reagents or catalysts, copper-dioxygen reactivity studies have received considerable attention.7-9,21,22 The use of copper complexes and dioxygen in organic oxidations is well established,22-27 but the emphasis (16) Sanchez-Ferrer, A.; Rodriguez-Lopez, J. N.; Garcia-Canovas, F.; GarciaCarmona, F. Biochim. Biophys. Acta 1995, 1247, 1-11. (17) Pidcock, E.; Obias, H. V.; Zhang, C. X.; Karlin, K. D.; Solomon, E. I. J. Am. Chem. Soc. 1998, 120, 7841-7847. (18) Itoh, S.; Kumei, H.; Taki, M.; Nagatomo, S.; Kitagawa, T.; Fukuzumi, S. J. Am. Chem. Soc. 2001, 123, 6708-6709. (19) Yamazaki, S.-i.; Itoh, S. J. Am Chem. Soc. 2003, 125, 13034-13035. (20) Klabunde, T.; Eicken, C.; Sacchettini, J. C.; Krebs, B. Nat. Struct. Biol. 1998, 5, 1084-1090. (21) Stack, T. D. P. Dalton Trans. 2003, 1881-1889. (22) Karlin, K. D.; Gultneh, Y. Prog. Inorg. Chem. 1987, 35, 219-327. J. AM. CHEM. SOC. 2005, 127, 5469-5483
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ARTICLES Scheme 1
on detailed mechanistic studies employing discrete copperdioxygen adducts is more recent.7,9 Oxidative N-dealkylation reactions of copper ligands are common,9 with those involving intramolecular ligand oxidations of CuIII2-bis-µ-oxo complexes by far being the best represented.28-31 From both theoretical32,33 and experimental (kinetic) arguments,28-31 it has been suggested that such reactions occur through an initial rate-limiting concerted proton-coupled electron-transfer (PCET) reaction (an ETPT reaction, often referred to as hydrogen atom abstraction (HAT), Scheme 2), as opposed to a consecutiVely occurring PCET (an ET/PT reaction, Scheme 2).34,35
dimers) through ET/PT-type pathways.39 Furthermore, for both phenolate oxygenation by a CuII2-(η2:η2-µ-peroxo) complex to give o-catechols40 and phenol oxidation promoted by a trinuclear Cu-dioxygen species,41 it is suggested that substrate coordination to the metal center is important for subsequent substrate oxidative transformations. Recently, we reported the synthesis, properties, and reactivity of a series of Cu2(O2) complexes, [{CuII(MePY2)R}2(O22-)]2+ (R ) H, MeO, and Me2N, 1R; Scheme 3), that contain copper Scheme 3
Scheme 2
Intermolecular exogenous substrate oxidations by Cu2-O2 species are less well documented.18,30,36-38 In studies by Itoh, it has been suggested that both CuII2-(η2:η2-µ-peroxo) and CuIII2-bis-µ-oxo complexes oxidize phenols (to coupled phenol (23) Oxidation in Organic Chemistry; Trahanovsky, W. S., Ed.; Academic Press: New York, 1973; Vol. Part B, Chapter 1. (24) Sprecher, C. A.; Zuberbu¨hler, A. D. Angew. Chem., Int. Ed. Engl. 1977, 16, 189. (25) Gampp, H.; Zuberbu¨hler, A. D. Met. Ions Biol. Syst. 1981, 12, 133-189. (26) Zuberbu¨hler, A. D. In Copper Coordination Chemistry: Biochemical and Inorganic PerspectiVes; Karlin, K. D., Zubieta, J., Eds.; Adenine: Guilderland, NY, 1983; pp 237-258. (27) Reglier, M.; Amadei, E.; Alilou, E. H.; Eydoux, F.; Pierrot, M.; Waegell, B. Bioinorg. Chem. Copper 1993, 348-362. (28) Mahapatra, S.; Young, V. G., Jr.; Kaderli, S.; Zuberbu¨hler, A. D.; Tolman, W. B. Angew. Chem., Int. Ed. Engl. 1997, 36, 130-133. (29) Mahadevan, V.; Hou, Z.; Cole, A. P.; Root, D. E.; Lal, T. K.; Solomon, E. I.; Stack, T. D. P. J. Am. Chem. Soc. 1997, 119, 11996-11997. (30) Taki, M.; Itoh, S.; Fukuzumi, S. J. Am. Chem. Soc. 2001, 123, 62036204. (31) Mahapatra, S.; Halfen, J. A.; Tolman, W. B. J. Am. Chem. Soc. 1996, 118, 11575-11586. (32) Cramer, C. J.; Kinsinger, C. R.; Pak, Y. THEOCHEM 2003, 632, 111120. (33) Cramer, C. J.; Pak, Y. Theor. Chem. Acc. 2001, 105, 477-480. (34) Cukier, R. I. J. Phys. Chem. B 2002, 106, 10089-10100. (35) Since the specifics of these reactions are unknown from a theoretical standpoint (i.e., we do not know if the electron and proton are going to the same (a hydrogen atom transfer (HAT)) or different (a concerted PCET) acceptor orbitals), we prefer to use Cukier’s more general nomenclature (ref 34) for thermodynamically coupled proton/electron-transfer reactions. Here, “ETPT” means that the ET and PT occur in one kinetically irresolvable step, while “ET/PT” designates that the ET and PT processes can be broken down into two kinetically resolvable steps, with the ET event occurring prior to proton transfer (PT). (36) Fukuzumi, S.; Ohtsu, H.; Ohkubo, K.; Itoh, S.; Imahori, H. Coord. Chem. ReV. 2002, 226, 71-80. (37) Mahadevan, V.; Henson, M. J.; Solomon, E. I.; Stack, T. D. P. J. Am. Chem. Soc. 2000, 122, 10249-10250. (38) Mahadevan, V.; DuBois, J. L.; Hedman, B.; Hodgson, K. O.; Stack, T. D. P. J. Am. Chem. Soc. 1999, 121, 5583-5584. 5470 J. AM. CHEM. SOC.
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ligated by para-substituted bispyridyl(ethylamine) ligands, (MePY2)R.42-44 These complexes are capable of oxidizing a variety of substrates in good yields, making them excellent (39) Osako, T.; Ohkubo, K.; Taki, M.; Tachi, Y.; Fukuzumi, S.; Itoh, S. J. Am. Chem. Soc. 2003, 125, 11027-11033. (40) Itoh, S.; Kumei, H.; Nagatomo, S.; Kitagawa, T.; Fukuzumi, S. J. Am. Chem. Soc. 2001, 123, 2165-2175. (41) Taki, M.; Teramae, S.; Nagatomo, S.; Tachi, Y.; Kitagawa, T.; Itoh, S.; Fukuzumi, S. J. Am. Chem. Soc. 2002, 124, 6367-6377.
Substrate Oxidation by Copper−Dioxygen Adducts
candidates for detailed mechanistic studies of Cu2-O2-mediated exogenous substrate oxidations.42 An initial study was published concerning PCET reactions between 1R and para-substituted N,N-dimethylanilines (R′-DMAs), which undergo N-dealkylations yielding [{CuII(MePY2)R}2(OH)2]2+ (2R), para-substituted methylanilines, and formaldehyde (Scheme 3).44 On the basis of linear-free energy and deuterium kinetic isotope effect (KIE) studies, we determined that both ET/PT and ETPT pathways are possible for these oxidations, with ET being rate limiting in the ET/PT case. For 1H, we suggested that all R′-DMA oxidations occurred through an ET/PT pathway, while there was a switch-over in the mechanism for R′-DMA oxidation by 1MeO and 1Me2N. Since the R′-DMA substrate is made more difficult to oxidize by one electron, the mechanism changes from ET/ PT to ETPT. In the present study, we disclose a much more detailed investigation on the mechanism of PCET reactions facilitated by 1R. Given that both KIEs and linear free-energy correlations can be difficult to interpret, we decided to further explore the nature of PCET reactions by 1R (i.e., ETPT versus ET/PT) using two mechanistic probes. Mechanistic probes are substrates that give unambiguous and different products depending on reaction pathways. The probes chosen for this study are N-cyclopropylN-methylaniline (CMA)45 and (p-methoxyphenyl)-2,2-dimethylpropanol (MDP).46 Here, the differential stabilities of radical (H• loss) versus radical cation (e- loss) intermediates formed following initial probe oxidation can allow us to differentiate between reaction pathways. To delineate the scope of 1R reactivity, we also present the reaction patterns of 1R toward substrates possessing both similar (i.e., 2,5-dimethyltetrahydrofuran (Me2THF), toluene, diethyl ether (Et2O)) and significantly weaker bond dissociation enthalpies (BDEs) (i.e., 9,10-dihydroanthracene (DHA) and 2,2,6,6-tetramethylpiperidin-1-ol (TEMPO-H)) compared to those of DMAs. Electrochemical and thermodynamic information for the 1R series is also presented to further aid us in gaining mechanistic insight for these oxidations. Furthermore, evidence for a pre-equilibrium involving substrate coordination to the metal center prior to oxidation is provided. Overall, the present study provides not only new insights but also a more detailed mechanistic picture concerning the mechanism of substrate oxidations by copper-dioxygen adducts. Experimental Section General Methods. All reactions were performed under an atmosphere of argon using standard Schlenk techniques. CuI complexes, [CuI(MePY2)H]B(C6F5)4, [CuI(MePY2)MeO]B(C6F5)4, and [CuI(MePY2)Me2N]B(C6F5)4, were prepared according to previously published procedures.42,44 Mechanistic probes, N-methyl-N-cyclopropylaniline (CMA),47 (p-methoxyphenyl)-2,2-dimethylpropanol (MDP),48 and TEMPO-H,49 as well as cyclopropylaniline (CA),50 (p-methoxyphenyl)-2,2dimethylpropanone (MDK),51 and N-methylquinolinium (MQ+) sul(42) (a) Zhang, C. X.; Liang, H.-C.; Kim, E.-i.; Shearer, J.; Helton, M. E.; Kim, E.; Kaderli, S.; Incarvito, C. D.; Zuberbu¨hler, A. D.; Rheingold, A. L.; Karlin, K. D. J. Am Chem. Soc. 2003, 125, 634-635. (b) Liang, H.-C.; Karlin, K. D.; Dyson, R.; Kaderli, S.; Jung, B.; Zuberbu¨hler, A. D. Inorg. Chem. 2000, 39, 5884-5894. (43) Henson, M. J.; Vance, M. A.; Zhang, C. X.; Liang, H.-C.; Karlin, K. D.; Solomon, E. I. J. Am. Chem. Soc. 2003, 125, 5186-5192. (44) Shearer, J.; Zhang, C. X.; Hatcher, L. Q.; Karlin, K. D. J. Am. Chem. Soc. 2003, 125, 12670-12671. (45) Shaffer, C. L.; Harriman, S.; Koen, Y. M.; Hanzlik, R. P. J. Am. Chem. Soc. 2002, 124, 8268-8274. (46) Baciocchi, E.; Bietti, M.; Lanzalunga, O. Acc. Chem. Res. 2000, 33, 243251.
ARTICLES fate,52 were all prepared through literature methods. NH4(B(C6F5)4) and NBu4(B(C6F5)4) were prepared by the method of Geiger; NR4Br underwent a metathesis reaction with Li(B(C6F5)4)‚Et2O (Boulder Scientific, Boulder, CO) in EtOH/H2O.53 Ferrocene, dimethylferrocene, ethylferrocene, decamethylferrocene, [FeII(phen)2(phen-NO2)](ClO4)2, N-methylaniline (MA), para-methoxybenzaldehyde (BA), 9,10-dihydroanthracene (DHA), and N,N-dimethylaniline (DMA) were all obtained through commercial sources and purified prior to use according to standard procedures.54 Solvents were purified using a commercially available double alumina column solvent purification system (Innovative Technologies, Inc.) and were degassed prior to use. All other reagents were used as received. Electronic absorption spectra were recorded on a Hewlett-Packard 8453 UV-vis spectrometer in a quartz optical Dewar using Schlenk cuvettes with a 1 cm path length. The methanol bath inside the Dewar was maintained at the desired temperature (within (0.1 °C) by cooling with a Neslab ULT-95 low-temperature circulating cooler. NMR spectra were recorded on a Bruker AMX 300 FTNMR spectrometer. EPR spectra were recorded in quartz EPR tubes on a Bruker EMX CWEPR spectrometer. The cavity was maintained at 65 K with the use of a He cryostat. Stopped-flow kinetic traces were recorded on a Hi-Tech SF-40 variable-temperature stopped-flow unit (1 × 0.2 cm quartz cell) equipped with a J&M-Tidas spectrometer. N,N-Dimethylaniline and Tetrahydrofuran (DMA and THF) Reaction Kinetic Analysis. Solutions of [{CuII(MePY2)R}2(O2)](B(C6F5)4)2 (1R) in CH2Cl2 ([1R] ranged between 4.0 × 10-5 and 6.5 × 10-5 M) were prepared by bubbling solutions of [CuI(MePY2)R]B(C6F5) in CH2Cl2 with dioxygen at low temperatures (-85 to -65 °C). UV-vis reaction monitoring was carried out using an apparatus with a quartz cuvette at one end of a long (14 in.) glass tube and airfree handling stopcocks and ground-glass joints at the other of which 10 in. is completely immersed in a cold methanol bath. After complete formation of 1R, as noted by the Abs at 355 nm (or 360 nm for 1Me2N), the solutions were purged of excess dioxygen with argon. A solution of DMA (500 µL) in CH2Cl2 was then slowly layered over the top of the reaction mixture by adding it down the side of the tube so that no solution mixing was obtained. After a brief period to allow for temperature equilibration, the reaction was initiated by mixing the solutions together with a gentle stream of argon, and then the reaction was monitored by UV-vis spectroscopy. For the higher-temperature reactions (-80 to -65 °C) involving DMA and 1Me2N, stopped-flow methods were used to follow the course of the reaction. Here, an O2saturated solution of CH2Cl2 was injected into a CH2Cl2 solution of [CuI(MePY2)Me2N]B(C6F5) and DMA, and the reaction was monitored. First-order rate constants for all DMA oxidation reactions were then extracted either manually using the change in Abs at 355 nm (360 nm for 1Me2N) or automatically using either SpecFit/32 (Spectrum Software Associates, Marborough, MA)55 or an in-house series of procedures written for Igor Pro 4.0 (Wavemetrics, Lake Oswego, OR). All three methods gave identical first-order rate constants (kobs). Data were collected at several different DMA concentrations (0.8-30 mM) over the temperature range of -65 to -85 °C. Plots of kobs-1 versus [DMA]-1 were then fit to a Lineweaver-Burk-type plot (eq 1):
kobs-1 ) kox-1 + (Keqkox)-1[DMA]-1
(1)
(47) Shaffer, C. L.; Morton, M. D.; Hanzlik, R. P. J. Am. Chem. Soc. 2001, 123, 349-350. (48) Baciocchi, E.; Bietti, M.; Putignani, L.; Steenken, S. J. Am. Chem. Soc. 1996, 118, 5952-5960. (49) Mader, E. A.; Larsen, A. S.; Mayer, J. M. J. Am. Chem. Soc. 2004, 126, 8066-8067. (50) Cui, W.; Loeppky, R. N. Tetrahedron 2001, 57, 2953-2956. (51) Smyth, T. P.; Corby, B. W. J. Org. Chem. 1998, 63, 8946-8951. (52) Hammond, P. R. U.S. Patent Appl. 566,924, November 9, 1984. (53) LeSuer, R. J.; Geiger, W. E. Angew. Chem., Int. Ed. 2000, 39, 248-250. (54) Armarego, C. Purification of Laboratory Chemicals, 5th ed.; Butterworth Heinemann: New York, 2003. (55) Gampp, H.; Maeder, M.; Meyer, C. J.; Zuberbu¨hler, A. D. Talanta 1985, 32, 95-110. J. AM. CHEM. SOC.
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ARTICLES Table 1. Product Yields in the Oxidation of Mechanistic Probes CMA and MDP (see Schemes 7, 8, and 10) by 1R in CH2Cl2 at -80 °C as Assessed by GC/MS Analysis 1H (%)
1MeO (%)
1Me2N (%)
PMAa MA CA MQ+ total yield of CMAb
Oxidation of CMA 20(5) 30(5) 48(2) 55(1) 6(1) 2(1)
