.
Angewandte
Communications
catalytic reduction of duroquinone by NADH/complex 1
entries 5 and 6 in Figure 3), with a maximum TON of 28.1
(
and a maximum TOF of 5.1. These values are about half those
for the reduction of menadione (entry 3). The presence of
three additional electron-donating methyl groups makes
duroquinone more difficult to reduce, which is in line with
[
12]
reported half-wave potentials.
As with menadione, one
mole of NADH reduces two moles of duroquinone (entry 6).
5
We also studied the reduction of quinones by NADH/[(h -
2
+
C Me C H )Ir(phen)(H O)] (3). The reaction pathways
5
4
6
5
2
were similar to those of complex 1 (Figure 2, and Figure S2
in the Supporting Information), showing that the phenyl
substituent on the Cp* has little effect on the reaction.
Since NADH is effectively a two-electron (hydride)
donor, it is surprising that the reduction of quinone appears
to involve two quantitative one-electron donor steps to give
the semiquinone product. Although one-step hydride transfer
from NADH and analogues to quinones (NADH + Q!
+
ꢀ
NAD + QH ), and multi-step hydride transfer (electron
ꢀ
+
ꢀ
transfer followed by proton/electron transfer, e + H + e )
have been previously described,
[
13]
no mechanism for the
reduction of quinone by metal-based hydrides has been
reported.
DFT calculations (see the Supporting Information for
details) were used to characterize various possible stationary
points to provide insight into the likely mechanism of the
iridium-catalyzed reduction of these quinones. A possible
mechanism for the catalytic reduction of quinone to semi-
quinone by NADH/complex 1 is shown in Scheme 3a. In the
first step, a hydride ion is transferred from NADH to
complex 1 to form the iridium–hydride complex 2 and
Scheme 3. Two possible mechanisms for the catalytic reduction of
duroquinone by complex 1. a) Reduction through two sequential one-
electron transfers. Figure S3 in the Supporting Information shows
II
7
a plot of the singly occupied molecular orbital of the Ir d complex.
b) Reduction through a single two-electron transfer. The pairs of
numbers associated with each step are potential-energy/free-energy
ꢀ
1
couples (in kcalmol ). The semiquinone has a pK of around 5 and is
a
therefore negatively charged at pH 7.2, whereas the quinol is protonat-
[
14]
ed (pK higher than 11).
+
a
NAD . One-electron transfer to the quinone together with
proton transfer to the phosphate buffer then generates the
ꢀ
II
II
deprotonated semiquinone radical (QC ) and a transient Ir
the transient Ir complex and the experimentally-detected
semiquinone. The alternative dihydroquinone pathway (Sche-
II
center. Next, an electron is transferred from Ir to a second
III
quinone molecule, resulting in further formation of semi-
me 3b), in which only Ir species are involved, appears not to
be viable theoretically.
ꢀ
III
quinone radical anion (QC ) and regeneration of Ir . The
assumed formation of semiquinone radical anions is based on
In conclusion, organometallic cyclopentadienyl–iridium
complexes offer the prospect of carrying out catalytic
reductions of quinones without an enzyme through hydride
transfer from NADH. These reactions produce semiquinones
rather than the two-electron reduced products, the dihydro-
quinones. DFT calculations suggest that the reactions occur
through a novel mechanism that involves an unusual transient
[
14]
their relatively low pK value (ca. 5). Subsequent coordi-
a
III
nation of a water molecule to the Ir center completes the
catalytic cycle. This oxidation state (II) is unusual for iridium
II [15]
and there are only a few reports of Ir .
The results of DFT calculations on an alternative two-
electron reduction pathway, which would give rise to the fully
reduced dihydroquinone, are shown in Scheme 3b. The
mechanism involves a one-step hydride transfer from com-
II
Ir state, in which the iridium center plays a key role in
promoting this one-electron pathway. This appears to be the
plex 2 to the quinone via an intermediate with an Irꢀ first report of a catalytic reduction of a quinone by an
C(quinone) bond. In this case, the quinol is released and
protons are taken up from the buffer because of the higher
organometallic complex, and may have promising potential
for the design of catalytic metallodrugs and for activation of
electron transfer in biological systems. Such organometallic
complexes may therefore be valuable for the modulation of
the redox status of cells (a potential drug target), as enzyme
mimics, and for biocoupled hydrogenation reactions.
[
16]
pK value of the dihydroquinol.
a
In both cases, the regeneration of the aqua complex is the
critical step. In Scheme 3a, this step appears favored on the
potential-energy surface, but disfavored on the free-energy
surface, and in Scheme 3b, this steps appears to be strongly
disfavored on both surfaces. Thus, notwithstanding the
Received: January 28, 2013
Published online: March 7, 2013
+
ꢀ
difficulties of modeling H /e transfers and the need to
invoke the phosphate buffer to balance the various reaction
steps, the DFT calculations generally support two consecutive
one-electron transfers (pathway in Scheme 3a), generating
Keywords: hydride transfer · iridium · NADH · quinones ·
.
radical reactions
4
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 4194 –4197