C O M M U N I C A T I O N S
Table 1. Products, Yields, and Rate Constants for Substrate
Oxidations Induced by 2R in Dichloromethane at -80 °C
References
a
a
a
(1) Que, L., Jr.; Tolman, W. B. Angew. Chem., Int. Ed. 2002, 41, 1114-
1137.
H
MeO
Me2N
9,10(DHA) f anthracene
THF f THF-OH
81%
67%
93%
82%
98%
84%
(2) Zhang, C. X.; Liang, H.-C.; Humphreys, K. J.; Karlin, K. D. In Catalytic
ActiVation of Dioxygen by Metal Complexes; Simandi, L., Ed.; Kluwer:
Dordrecht, The Netherlands, 2002; pp Chapter 2, pp 79-121. In press.
(3) Solomon, E. I.; Chen, P.; Metz, M.; Lee, S.-K.; Palmer, A. E. Angew.
Chem., Int. Ed. 2001, 40, 4570-4590.
(4) Karlin, K. D.; Zuberbu¨hler, A. D. In Bioinorganic Catalysis, 2nd ed.,
revised and expanded; Reedijk, J., Bouwman, E., Eds.; Marcel Dekker:
New York, 1999; pp 469-534.
2(1) × 10-5 7(1) × 10-4 3(1) × 10-2
DMA f N-methylaniline + CH2dOb 69%
PhCH2OH f PhCHdO
Ph2CHOH f Ph2CdO
MeOH f CH2)O
83%
88%
92%
38%
96%
72%
79%
31%
quant.
quant.
37%
5(1) × 10-5 9(1) × 10-4 1(1) × 10-1
(5) Liang, H.-C.; Zhang, C. X.; Henson, M. J.; Sommer, R. D.; Hatwell, K.
R.; Kaderli, S.; Zuberbuehler, A. D.; Rheingold, A. L.; Solomon, E. I.;
Karlin, K. D. J. Am. Chem. Soc. 2002, 124, 4170-4171.
(6) Tolman, W. B. Acc. Chem. Res. 1997, 30, 227-237.
(7) Mahadevan, V.; Henson, M. J.; Solomon, E. I.; Stack, T. D. P. J. Am.
Chem. Soc. 2000, 122, 10249-10250.
a Top values are yields determined by GC, and bottom values are pseudo-
first-order reaction rate constants given in s-1 b Based on the amount of
.
N-methylaniline produced.
(8) See Supporting Information.
low yields and side products). The oxidation of THF has never
been observed with a copper species, but with 2R this reaction is
both high-yielding (Table 1) and results in mainly THF-OH
formation.20 When THF is oxidized with 18O-incorporated 2R, over
80% of the THF-OH formed contains an 18OH moiety, indicating
that the hydroxylation of THF involves the transfer of oxygen from
the dicopper complex to the substrate. There is a dramatic
substituent effect; yields of THF-OH increase and oxidation rates
are enhanced by ∼1500-fold (Table 1) as the ligand 4-pyridyl group
is made more electron-donating.34
N,N′-Dimethylaniline (DMA) was also examined as a substrate
for 2R. Extensive work has been accomplished using DMA as a
substrate for oxidation events in cytochrome P450 metallo-
enzymes,21-23 and models.24 Intramolecular oxidative N-dealkyla-
tions have been observed in CuII2-O2 species (i.e., ligand
degradation),25-27 but DMA has never been used as a potential
substrate for CunOn complexes. Solutions of 2R all readily oxida-
tively N-dealkylate DMA, forming methylaniline, formaldehyde,
and 3R in excellent yields, with 2Me2N being the significantly more
efficient oxidant (Table 1).
(9) Sanyal, I.; Mahroof-Tahir, M.; Nasir, S.; Ghosh, P.; Cohen, B. I.; Gultneh,
Y.; Cruse, R.; Farooq, A.; Karlin, K. D.; Liu, S.; Zubieta, J. Inorg. Chem.
1992, 31, 4322-4332.
(10) Karlin, K. D.; Haka, M. S.; Cruse, R. W.; Meyer, G. J.; Farooq, A.;
Gultneh, Y.; Hayes, J. C.; Zubieta, J. J. Am. Chem. Soc. 1988, 110, 1196-
1207.
(11) Obias, H. V.; Lin, Y.; Murthy, N. N.; Pidcock, E.; Solomon, E. I.; Ralle,
M.; Blackburn, N. J.; Neuhold, Y.-M.; Zuberbu¨hler, A. D.; Karlin, K. D.
J. Am. Chem. Soc. 1998, 120, 12960-12961.
(12) Henson, M., J.; Vance, M. A.; Zhang, C. X.; Liang, H.-C.; Karlin, K. D.;
Solomon, E. I., submitted for publication. Making the 4-pyridyl group
more electron-donating slightly increase the amount of bis-µ-oxo-CuIII
present in solution.
2
(13) Liang, H.-C.; Karlin, K. D.; Dyson, R.; Kaderli, S.; Jung, B.; Zuberbu¨hler,
A. D. Inorg. Chem. 2000, 39, 5884-5894.
(14) Karlin, K. D.; Kaderli, S.; Zuberbu¨hler, A. D. Acc. Chem. Res. 1997, 30,
139-147.
(15) X-ray structures have been obtained for R ) H, MeO, and Me2N. General
oxidation procedure: 10 equiv of substrate in a CH2Cl2 solution of 2R at
-80 °C overnight, followed by quenching with pentane.
(16) MacDonnell, F. M.; Fackler, N. L. P.; Stern, C.; O’Halloran, T. V. J.
Am. Chem. Soc. 1994, 116, 7431-2.
(17) Kelm, H.; Kru¨ger, H.-J. Angew. Chem., Int. Ed. 2001, 40, 2344-2348.
(18) Reetz, M. T.; Toellner, K. Tetrahedron Lett. 1995, 36, 9461-4.
(19) LeCloux, D. D.; Barrios, A. M.; Lippard, S. J. Bioorg. Med. Chem. 1999,
7, 763-772.
(20) Only small amounts of γ-butrylactone (<1% yields by GC) are obtained
from the reaction of 2R and THF, indicating that oxidation of THF-OH is
not a major oxidation pathway in the formation of 3R from solutions of
THF.
Benzyl alcohol and benzhydrol, which have previously been
utilized in CuII -On substrate oxidation chemistry,28-32 are both
n
readily oxidized by 2R to benzaldehyde and benzophenone,
respectively. Surprisingly, the relatively inert alcohol methanol31
is also oxidized by dichloromethane solutions of 2R. Only the
2-electron oxidation products are obtained (aldehydes and ketones),
with no further oxidation products observed. The general trends in
reactivity of 2R follows that noted above; as R is made more
electron-donating, yields substantially improve, and oxidation rates
increase by ∼2000× going from R ) H to R ) Me2N (Table 1).
In summary, we have shown for the first time clear ligand
electronic influences on the formation and subsequent reactivity
of dioxygen adducts of copper(I) complexes with tridentate ligands.
In particular, 2Me2N exhibits exceptionally high reactivity toward
newly examined and interesting exogenous substrates such as THF
and DMA. It will be of interest to determine the origin of the
enhanced reactivity for 2Me2N relative to those of 2MeO and 2H.12,33
(21) Bhakta, M. N.; Wimalasena, K. J. Am. Chem. Soc. 2002, 124, 1844-
1845.
(22) Shaffer, C. L.; Harriman, S.; Koen, Y. M.; Hanzlik, R. P. J. Am. Chem.
Soc. 2002, 124, 8268-8274.
(23) Manchester, J. I.; Dinnocenzo, J. P.; Higgins, L. A.; Jones, J. P. J. Am.
Chem. Soc. 1997, 119, 5069-5070.
(24) Baciocchi, E.; Lanzalunga, O.; Lapi, A.; Manduchi, L. J. Am. Chem. Soc.
1998, 120, 5783-5787.
(25) Mahapatra, S.; Halfen, J. A.; Tolman, W. B. J. Am. Chem. Soc. 1996,
118, 11575-11586.
(26) Zhang, C. X.; Liang, H.-C.; Kim, E.-i.; Gan, Q.-F.; Tyekla´r, Z.; Karlin,
K. D.; Lam, K.-C.; Rheingold, A. L.; Kaderli, S.; Zuberbu¨hler, A. D.
Chem. Commun. 2001, 631-632.
(27) Taki, M.; Teramae, S.; Nagatomo, S.; Tachi, Y.; Kitagawa, T.; Itoh, S.;
Fukuzumi, S. J. Am. Chem. Soc. 2002, 124, 6367-6377.
(28) Jazdzewski, B. A.; Tolman, W. B. Coord. Chem. ReV. 2000, 200-202,
633-685.
(29) Mahadevan, V.; Klein Gebbink, R. J. M.; Stack, T. D. P. Curr. Opin.
Chem. Biol. 2000, 4, 228-234.
(30) Itoh, S.; Taki, M.; Fukuzumi, S. Coord. Chem. ReV. 2000, 198, 3-20.
(31) Chaudhuri, P.; Hess, M.; Mueller, J.; Hildenbrand, K.; Bill, E.; Weyher-
mueller, T.; Wieghardt, K. J. Am. Chem. Soc. 1999, 121, 9599-9610.
(32) Mirica, L. M.; Vance, M.; Rudd, D. J.; Hedman, B.; Hodgson, K. O.;
Solomon, E. I.; Stack, T. D. P. J. Am. Chem. Soc. 2002, 124, 9332-
9333.
Acknowledgment. Financial support of this research was
provided by the National Institutes of Health (K.D.K., GM28962;
M.E.H., postdoctoral fellowship GM20805) and the Swiss National
Science Foundation (A.D.Z.).
(33) The increased amount of bis-µ-oxo-CuIII2 in solution (ref 12) alone cannot
account for the >3 order of magnitude increase in oxidation rates.
(34) It appears that trace water is required for this reaction, to proceed to final
bis-hydroxo complex 3R (Scheme 1), and primary isotope effects are
observed (for THF vs THF-d8), indicating that the reaction is proceeding
via a rate-limiting oxidative C-H bond cleavage. Studies are in progress.
Supporting Information Available: Contains a detailed Experi-
mental Section, UV/vis spectra of 2H, 2MeO, and 2Me2N, and kinetics
plots (PDF). Crystallographic data for 1Me2N and 1MeO (CIF). This
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