Mechanistic investigations of the iridium(III)-catalyzed aerobic oxidation of primary and secondary alcohols

Article abstract of DOI:10.1021/ja8049595

The commercially available catalysts [(Cp*IrCl₂)₂] is employed with O₂ as the terminal oxidant in the presence of catalytic amounts of Et₃N for the aerobic oxidation of primary and secondary alcohols. A new mechanism for the Ir-catalyzed aerobic oxidation is also presented that suggests that the transition metal maintains its +3 oxidation state throughout the entire catalytic cycle. Copyright

Full text of DOI:10.1021/ja8049595

Published on Web 10/09/2008
Mechanistic Investigations of the Iridium(III)-Catalyzed Aerobic Oxidation of
Primary and Secondary Alcohols
Bi Jiang, Yuee Feng, and Elon A. Ison*
Department of Chemistry, North Carolina State UniVersity, 2620 Yarbrough DriVe,
Raleigh, North Carolina 27695-8204
Received June 27, 2008; E-mail: eaison@ncsu.edu
Catalytic aerobic oxidations remain appealing because of the low
cost and availability of molecular oxygen. Recently, the chemistry
Table 1. Dependence of Oxidation of 4-Methoxybenzyl Alcohol on
1
O2
a
b
of “chemical oxidases” has seen renewed interest especially in the
reaction conditions
% conversion
TON
2
area of Pd-catalyzed oxidations. These discoveries have regenerated
O2 (1 atm)
Air (1atm)
N2 (1 atm)
96
24
12
38
9.6
4.8
interest in the design of new metal systems that undergo similar
green oxidations”. A problem in some Pd-catalyzed oxidations is
“
the decomposition of the homogeneous catalyst into inactive bulk
metal. This decomposition pathway competes with the slow addition
of dioxygen to Pd(0).
a
Conditions: Run using 2.5 mol % 1, substrate (2M), Et3N (2M),
b
1
1
2 h, 80 °C, C7D8. Determined by H NMR spectroscopy.
3
One way to alleviate this problem is to rationally design catalytic
systems that employ transition metals that readily activate dioxygen.
Oxidative addition reactions of d Ir(I) complexes are well-known
of 1 with 4-methoxybenzyl alcohol under three different conditions:
(a) 1 atm of O , (b) 1 atm of air, and (c) 1 atm of N , (Table 1).
2
2
8
These data clearly show that O is essential for catalytic turnover
2
in organometallic chemistry. Further, the activation of O
iridium(I) complexes has been demonstrated. Despite this fact,
catalytic oxidations that employ Ir are scarce. One notable exception
2
by
for these catalysts.
4
The scope of reactivity was then investigated using 1 as a catalyst
in toluene at 80 °C (Supporting Information, Table S1). There is a
clear electronic dependence on the reactivity of parasubstituted
benzyl alcohols (entries S1-S6) with the reaction favoring electron
donating substituents. Aliphatic and secondary alcohols (entries
S7-S8) are all successfully oxidized under the reaction conditions.
Dioxygen uptake measurements were performed and reveal a
substrate/dioxygen stoichiometry of 2.8(7):1. The dioxygen stoi-
chiometry suggests that hydrogen peroxide does not accumulate
during the catalytic reaction as observed in other palladium-
5
is the Oppenauer-type oxidations developed by Yamaguchi et al.
In this reaction, secondary alcohols are oxidized to ketones, while
acetone is sacrificially reduced. In the proposed mechanism for this
reaction acetone inserts into an Ir(III) hydride to form an alkoxide
ligand that subsequently undergoes alcohol exchange to yield
isopropyl alcohol and regenerate the catalytically active Ir complex.
We rationalized that this strategy could potentially be used in
2
aerobic oxidations, where O instead of acetone, serves as a
hydrogen acceptor. Recently the groups of Ikariya et al. and
7
catalyzed oxidation reactions. Attempts to use hydrogen peroxide
Rauchfuss et al. independently reported on the reactivity of Ir
directly as an oxidant resulted instead in the rapid disproportionation
of H O under the reaction conditions.
6
2
hydrides with O . Here we report that simple Ir complexes catalyze
2
2
the oxidation of primary and secondary alcohols. In these reactions
is directly reduced to H O according to equation 1.
The progress of the aerobic oxidation of benzyl alcohol with O2
catalyzed by 1 (eq 1) was investigated by monitoring the change
in oxygen pressure within a sealed, temperature-controlled Parr
reaction vessel equipped with a high-accuracy pressure transducer,
and a digital recorder. From the kinetic data, the reaction exhibited
O
2
2
2
first-order dependencies on [catalyst] and [O ], saturation kinetics
on [benzyl alcohol], and no dependence on [triethyl amine] (Figure
1).
We also report initial mechanistic analyses of this reaction and
comment on the implications for similar transition-metal-catalyzed
aerobic oxidations. The highlights of our system are the following:
(
1) it offers mechanistic insight on activation of oxygen by transition
metal complexes, (2) the reaction illustrates a new role for catalysis
by Ir, and (3) the reaction utilizes the environmentally benign O
2
as a stoichiometric oxidant. This last feature is very attractive
because it limits the amount of organic waste typically generated
by traditional organic oxidants and does not lead to environmentally
hazardous byproducts typically associated with stoichiometric
transition metal oxidants. Also notable is the simplicity of our
catalytic system; all aerobic oxidations are performed with the
2
The aerobic oxidation of benzyl alcohol (R,R-d ) catalyzed by 1
allowed us to obtain a kinetic isotope effect for the catalytic reaction
of 0.9(1). Further the aerobic oxidation of a mixture of benzyl
alcohol (R,R-d
deuterium scrambling and the formation of benzyl alcohol (R-d
as well as benzaldehyde (R-d ) and benzaldehyde (Scheme 1). The
2
) and benzyl alcohol resulted in the complete
1
),
commercially available Ir(III) complex, [Cp*IrCl
ally utilized in C-H activation and catalytic hydrogenations, and
transfer hydrogenations) at 1 atm O , and catalytic amounts of Et N.
One of our main hypotheses was that O is needed for direct
catalytic turnover. We tested this by examining the catalytic reaction
2 2
] , (1), (tradition-
1
kinetic isotope effect and isotopic labeling data strongly suggests
the presence of Ir hydrides as key species in the catalytic cycle.
To investigate the catalytic viability of these species we
investigated the oxidation of 4-methoxybenzyl alcohol with 1 under
2
3
2
1
4462 9 J. AM. CHEM. SOC. 2008, 130, 14462–14464
10.1021/ja8049595 CCC: $40.75  2008 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. (a) Time profile for the aerobic oxidation of benzyl alcohol (1 M) with O2 (14.5 psig), Et3N (25.1 mM), and 1 (12.6 mM) in toluene at 353 K.
(
b) Dependence of kobs on [benzyl alcohol] for the oxidation of benzyl alcohol with O2 (14.5 psig), Et3N (25.1 mM), [1] (12.6 mM). Data are fit with
8 2
nonlinear least-squares fitting to an equation describing saturation in [benzyl alcohol], R ) 0.996. (c) Dependence on [1]: O2 (14. 5 psig), Et3N (25.1 mM),
[
2
benzyl alcohol], (1 M) R ) 0.997. (d) Dependence on [Et3N]: O2 (14. 5 psig), [1] (12.6 mM), benzyl alcohol (1 M) in toluene at 353 K.
Scheme 1
after 12 h. In contrast, the aerobic oxidation of benzyl alcohol
catalyzed by 2 resulted in a similar TON (14) after 12 h for the
catalytic reaction. Further, the kinetic competency 2 is comparable
1
0
to 1 under similar catalytic conditions.
These results strongly implicate the Ir-hydride 2 as a key
intermediate in the catalytic cycle for the aerobic oxidation of
alcohols. The dihydride 3 is a minor species that is not part of the
catalytic cycle. The treatment of 2 with benzaldehyde and Et
3
NHCl
in C under nitrogen at 80 °C results in the formation benzyl
7
D
8
alcohol and 1. The reaction rapidly reaches equilibrium in 2 h with
the ratio of benzyl alcohol/benzaldehyde (1:1.3). The data suggest
that in the absence of oxygen, 2 readily reduces benzaldehyde. A
plausible mechanism and rate equation that is consistent with the
Scheme 2
1
0
data presented is depicted in Scheme 3 and eq 3.
Scheme 3
7 8 2
nitrogen. Treatment of a C D solution of 1 under N with excess
4
-methoxybenzyl alcohol (1-16 equiv) results in the formation of
two new hydride species Ir-H (δ -13.5, -13.8 ppm) in a 6:1 ratio
(
[
Scheme 2). The new species were assigned as the complexes
(Cp*Ir Cl) HCl], 2, and [Cp*IrHCl] , 3. The concentration of 3
2
2
increased as the concentration of 4-methoxybenzyl alcohol is
increased. Also, in the presence of excess alcohol, 2 is slowly (24
h) converted to 3. Complexes 2 and 3 have been previously
9
synthesized from 1 by Maitlis and co-workers. We examined the
-dP(O2)
Rate )
)
viability of these species as intermediates by examining their
reactivity and their kinetic competency in the oxidation of benzyl
alcohol.
dt
K k k [RCH OH][(Cp * IrCl ) ] [O ]
1
2
3
2
2 2 T
2
(3)
k-2[RCHO][Et NHCl] + K k [RCH OH][Et N]
3
1
2
2
3
3 2 7 8
Treatment of 3 with Et NHCl and O in C D results in the
decomposition to several unidentified species. Further, the aerobic
The formation of 2 is rapid relative to the overall time scale of
oxidation of benzyl alcohol catalyzed by 3 resulted in a TON of 2
the catalytic reaction. This is confirmed by the observation that
J. AM. CHEM. SOC. 9 VOL. 130, NO. 44, 2008 14463

C O M M U N I C A T I O N S
1
when 1 is treated with benzyl alcohol no change in the H NMR
or UV spectrum of 1 is observed at room temperature. However,
maintains its (+3) oxidation state throughout the entire catalytic
cycle. Evidence in support of the mechanism presented includes
when this mixture is treated with Et
benzaldehyde is immediately formed along with 2. Also notable,
is the fact that there is no catalytic activity in the absence of Et N.
Thus the role of Et N in the catalytic reaction is to promote
-hydride elimination of the coordinated alcohol and the formation
of 2. The observation that under nitrogen and in the presence of
Et NHCl benzaldehyde is reduced by 2 suggests that the product
3
N, a stoichiometric amount of
2
(1) demonstration that O is needed for catalytic turnover, (2) kinetic
data from oxygen uptake experiments consistent with the proposed
mechanism, (3) kinetic isotope and isotopic labeling data that
implicate Ir hydrides as key intermediates in the catalytic reaction,
(4) identification of the Ir hydride 2 as a key and kinetically
competent intermediate in the catalytic cycle, and (5) identification
3
3
ꢀ
3
2
of the reaction of 2 with O as the turnover limiting step in the
forming step in Scheme 3 is reversible. Also the observed formation
of benzaldyde (12% conversion) in Table 1 in the absence of oxygen
results from the stoichiometric oxidation of benzyl alcohol by 1
prior to catalytic turnover. During the catalytic reaction, 2 is
observed as the resting state of the catalytic system. Thus the role
reaction and the identification of 2 as the resting state of the catalytic
system. The results presented will aid in the development of more
efficient systems for aerobic oxidations with Ir and other transition
metals.
Acknowledgment. This work was supported by North Carolina
State University, ACS-PRF, and the ORAU Ralph E. Powe Junior
Faculty Enhancement Award.
of O
2
in this catalytic reaction is to promote catalytic turnoVer;
that is, dioxygen acts as a hydrogen atom acceptor similar to recent
“
chemical oxidases”.
The absence of a kinetic isotope effect, the identification of 2 as
Supporting Information Available: Experimental details and
kinetic data. This material is available free of charge via the Internet
at http://pubs.acs.org.
the catalyst resting state, and the first order dependence of [O
2
] are
consistent with the reaction of O with 2 as the turnover limiting
2
step. The first-order dependence on [catalyst] is not consistent with
the monomerization of 2. Nor is the data consistent with the
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1
1
reduction of Ir(III) to Ir(I). Heating a C
7 8
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(
the reaction of an Ir hydride with O
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2
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2
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2
12
to produce transition metal hydroperoxide complexes. Studies on
(
2 2
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2
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that can avoid lower valent oxidation states altogether (in this case
Ir(I)).
To summarize we have presented a novel catalytic system for
the aerobic oxidation of primary and secondary alcohols. For these
reactions we employ the commercially available catalysts
(
1
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(10) See Supporting Information for derivation.
11) This is in stark contrast to a similar aerobic oxidation reported by
(
+
Gabrielsson
and
co-workers
with
[Cp*Ir(Cl)(bpy)] ,
and
+
[Cp*Ir(H)(bpym)] . The authors in this case propose the formation of Ir(I).
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(
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[
(Cp*IrCl
catalytic amounts of Et
aerobic oxidation is also presented that suggests the transition metal
2
)
2
] with O
2
as the terminal oxidant in the presence of
2
904–2907.
3
N. A new mechanism for the Ir-catalyzed
JA8049595
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4464 J. AM. CHEM. SOC. 9 VOL. 130, NO. 44, 2008