C O M M U N I C A T I O N S
Table 1. Percentage of 18O Incorporation into Alcohol Products by
feature of these nonheme iron catalysts. Thus, the alkyl radical can
in principle rebound with either OH group, the outcome of which
determines the %H218O incorporation. Given that these values range
from 40% for cyclohexane-d12 to 79% for cis-DMCH, the energy
difference between the two possible rebound trajectories is <2 kcal
mol-1, which is consistent with DFT calculations.8 Thus, the
labeling results indicate that 2°-alkyl radicals do not discriminate
between the two OH groups, but 3°-alkyl radicals favor rebound
with the OH group derived from water. Perusal of the structure of
1 (Figure 1) suggests steric effects may provide a possible rationale
for this preference since the hemisphere surrounding O1 is less
sterically congested.
Fe(L) Catalysts in the Presence of 1000 equiv of H218O
substrate
Me2PyTACN
TPA4b
cyclohexane
cyclohexane-d12
cyclooctane
cis-DMCH (3° C-H)
adamantane (3° C-H)
2,3-dimethylbutane
42
40
44
79
74
76
29
35
23
6
6
Scheme 2
In conclusion, 1 is an efficient alkane hydroxylation catalyst that
can incorporate surprisingly large amounts of water into products
via an unusual rebound-like mechanism. A similar mechanism may
be operating in the hydroxylation of indane to 1-indanol by toluene
or naphthalene dioxygenase to account for the high level of H218O
incorporation (68%) found.9 In addition, the R-ketoglutarate-
dependent halogenases represent an established biological example
in which C-H bond cleavage initiated by an FedO moiety is
consummated by rebound not with the incipient OH group but with
the adjacent halide ligand.10 Thus, 1 may serve as a model for this
unusual enzymatic chemistry, which suggests that a broader
mechanistic landscape than in heme systems applies to nonheme
sites.
Surprisingly, even higher levels of H218O incorporation (76 (
3%) were obtained for alcohol products in the oxidation of alkanes
with tertiary C-H bonds, such as adamantane, cis-DMCH, and 2,3-
dimethylbutane. Furthermore, this unexpectedly large value was
found to be independent of substrate concentration (25-1000 mM).
This observation strongly implicates the HO-FeVdO species as
the only oxidant capable of alkane oxidation in the case of 1.
The labeling results for 1 differ significantly from those reported
for Fe(TPA) (Table 1). For the latter catalyst, label incorporation
from H218O into substrates with 2° C-H bonds decreased with the
C-H bond strength and labeling of 2°-ol products was much higher
than for 3°-ol products. These results suggested that C-H bond
cleavage and oxo-hydroxo tautomerism were competitive processes,
as also found for iron porphyrin complexes.4b,5,6 However, this was
not the case for 1 since higher water incorporation was observed
in the oxidation of the weaker 3° C-H bonds, and this level of
incorporation was independent of cis-DMCH concentration. To
rationalize the high level of label incorporation, we considered the
possibility that a carbocation intermediate was formed and subse-
quently trapped by water, but discarded it because of the high
retention of configuration observed for cis-DMCH hydroxylation.
We also considered the possibility that the HO-FeVdO oxidant
became doubly labeled by rapid, multiple intermolecular exchanges
with H218O, but rejected it on the basis of a H218O-labeling
experiment where cyclohexane and cis-DMCH were oxidized in
competition with each other. cis-DMCH reacted much faster than
cyclohexane, and so should have a shorter lived oxidant. Neverthe-
less, the 3°-ol thus formed contained 74% label from water, while
cyclohexanol contained only 38%. Thus, the difference in label
incorporation cannot be determined by how much 18O is present in
the common FeV oxidant, and a modified mechanistic scenario is
required for 1.
Acknowledgment. Financial support from MCYT of Spain
(CTQ2006-05367/BQU to M.C.) and from US-DOE (DE-FG02-
03ER15455 to L.Q.) is gratefully acknowledged. A.C., L.G., and
M.G. thank MEC for Ph.D. grants.
Supporting Information Available: Experimental procedures for
the preparation of 1 and for the oxidation reactions and the cif file for
1. This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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In Scheme 2, we propose a scenario in which the structure of
the substrate can play a role in determining the course of C-O
bond formation. For 1, the two FeV(O)(OH) isomers (A and B) in
equilibrium via oxo-hydroxo tautomerism are distinct since the
ligands trans to the oxo and hydroxo groups are not chemically
equivalent and the orientations of the pyridine ligand relative to
the FedO bond are different. No matter which isomer abstracts
the H atom from substrate, a common FeIV(OH)2 species is formed.
The cis configuration of the two hydroxo groups differs from the
trans configuration required in heme complexes and is a unique
(8) DFT calculations were done using cyclohexane as a substrate. Geometries
were optimized at the B3LYP level in junction of the LANL2DZ basis
set with associated ECP for Fe. The energies were further refined by single-
point calculations using the SDD basis set with associated ECP for Fe
and 6-311G(d,p) basis sets on the other atoms as implemented in the
Gaussian 03 program.
(9) Wackett, L. P.; Kwart, L. D.; Gibson, D. T. Biochemistry 1988, 27, 1360-
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(10) Galonic, D. P.; Barr, E. W.; Walsh, C. T.; Bollinger, J. M., Jr.; Krebs, C.
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