Discovery of and mechanistic insight into a ligand-modulated palladium-catalyzed wacker oxidation of styrenes using TBHP

Article abstract of DOI:10.1021/ja043203m

We describe the discovery of a new N-heterocyclic carbene-modulated Pd catalyst for the Wacker oxidation that does not require molecular oxygen but instead uses TBHP as a reagent in this oxidation. The catalyst activity and selectivity for the oxidation of styrene derivatives to methyl ketones are among the best reported. Preliminary mechanistic studies of the catalytic system were performed and show that the origin of the carbonyl oxygen is TBHP and that the hydrogens in the product all originate from the starting olefin. Copyright

Full text of DOI:10.1021/ja043203m

Published on Web 02/10/2005
Discovery of and Mechanistic Insight into a Ligand-Modulated
Palladium-Catalyzed Wacker Oxidation of Styrenes Using TBHP
Candace N. Cornell and Matthew S. Sigman*
Department of Chemistry, UniVersity of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-8500
Received November 11, 2004; E-mail: sigman@chem.utah.edu
The oxidation of terminal olefins to methyl ketones with Pd(II)
complexes, known as the Wacker oxidation, is a well-established
synthetic transformation used in the production of acetaldehyde on
1
an industrial scale. Classically, this reaction requires catalytic Pd-
2
(II) and stoichiometric CuCl under aerobic conditions. Chlorinated
byproducts and palladium decomposition limit the exploitation of
the Wacker oxidation.1 Many modifications have been developed
allowing for oxidation of more complex targets, but most still utilize
a
1c
the addition of a copper cocatalyst. Copper additives severely limit
the use of ligands with Pd. Ligand modulation of Pd catalysis has
proven to be vital in the development of more effective and
asymmetric catalysts for the mechanistically related aerobic alcohol
oxidation.2 Consequently, we were interested in developing a
catalytic system for the Wacker oxidation that would alleviate the
3
need for copper additives. We report herein the discovery and
preliminary mechanistic considerations of a promising new N-
heterocyclic carbene-modulated Pd-catalyzed Wacker oxidation that
uses tert-butylhydroperoxide (TBHP).
2 2
The effectiveness of Pd(IiPr)(OAc) ‚(H O) (1) in aerobic alcohol
oxidations led us to test this catalyst for the Wacker oxidation of
styrene. Styrene derivatives are generally problematic substrates
for these oxidations due to polymerization or oxidative cleavage
to benzaldehyde and/or benzoic acid.1b,4 Oxidation of styrene with
Figure 1. In situ FTIR monitoring the disappearance of styrene via C-H
-
1
out of plane deformation at 702.9 cm and formation of γ-butyrolactone
-
1
via the CO stretch at 1779.5 cm
.
2
.5 mol % 1 at 0.3 M in THF leads primarily to acetophenone
8
M substrate in MeOH at 35 °C. Several styrene derivatives were
tested to explore the initial scope of this method (Table 1). High
selectivity for the oxidation of primary aryl olefins to ketones
(>95%) is demonstrated with minimal observed aldehyde formation.
Different substitution patterns on the aryl ring lead to similar yields
(entries 2 and 3). A sterically hindered olefin converts more slowly
to the methyl ketone but, again successful oxidation is observed
(entry 5). Electronics play a minimal role where 3-nitrostyrene only
requires a slight increase in catalyst loading for competent oxidation
with 95% conversion at 24 h (Figure 1). Monitoring the reaction
via in situ FTIR spectroscopy reveals a ca. 10 h induction period,
which was presumed due to the formation of an active catalyst
species. To explore if the active catalyst was cationic in nature, a
range of counterions was evaluated. Less basic counterions show
a significant decrease in induction period. Optimization of the
reaction solvent illustrated the unusual nature of this oxidation in
which THF proved to be the only competent reaction solvent. Of
note, no oxidation was observed in 2,2,5,5-tetramethyl-THF. On
further examination of the in situ FTIR data, two other carbonyl
stretches were observed and attributed to γ-butyrolactone and
succinic dialdehyde, products of THF oxidation. Additionally, the
THF oxidation rate is qualitatively similar to that of the Wacker
oxidation.
One plausible explanation of these data is that a cationic Pd
complex catalyzes an aerobic oxidation of THF to 2-tetrahydrofuryl
hydroperoxide. The peroxide can then act as a reagent or an oxidant
in the Wacker process. This type of coupled oxidation has been
5
6
7
(
entry 7). The high versatility of the system is showcased where
trans-stilbene, an internal olefin, is oxidized in an aprotic, nonpolar
solvent though significant levels of oxidative cleavage to benzal-
dehyde are observed (entry 8).9
,10
A question this system provokes is, why are peroxides needed
for this transformation while a related catalyst utilizes O for alcohol
2
oxidation? To begin probing this question, mechanistic studies were
undertaken. Kinetic studies reveal an overall zero-order reaction
with a first-order dependence on [Pd(IiPr)(OTf) ] (0.3-6.0 mol %)
2
4c
previously observed by Alper and co-workers. To test if a peroxide
is involved in the catalysis, styrene was submitted to catalytic Pd-
and a zero-order dependence on both [styrene] (0.3-0.9 M) and
[TBHP] (3-12 equiv).11 Use of anhydrous TBHP in MeOH led
12
(
IiPr)(OTs)
2
and 5 equiv of TBHP in toluene under anaerobic condi-
2
to an inverse first-order dependence on [H O] (0.5-12 M). The
tions. Complete conversion of styrene to >97% acetophenone was
observed without an induction period. This is especially noteworthy
since other Wacker oxidations of styrenes, which do not utilize a
ligand on Pd, lead to considerable levels of oxidative cleavage.4
Optimization led to the following conditions: 0.75 mol % [Pd-
resulting empirical rate law supports rate-limiting dissociation of
water from a palladium catalyst.13 The X-ray crystallographic
2
analysis of Pd(IiPr)(OTf) of the ground-state structure shows dative
bonds from three molecules of water to Pd (Figure 2). This supports
a mechanism wherein water dissociation is necessary prior to
substrate binding.
2 2
(IiPr)Cl ] (2), 3.2 mol % AgOTf, 5.5 equiv of TBHP(aq), and 0.5
2796
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J. AM. CHEM. SOC. 2005, 127, 2796-2797
10.1021/ja043203m CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
phenone. Incomplete 16O incorporation can be attributed to the fast
rate of isotopic washing under the reaction conditions.
Table 1. Wacker Oxidation of Styrene Derivatives
1
5
To determine if a 1,2-hydride shift mechanism is plausible, R-D-
styrene (>95% R-D) was submitted to the Wacker oxidation.
Utilizing 2.0 mol % Pd(IiPr)(OTf) afforded 81% incorporation of
2
the deuterium label. This showcases that the dominant pathway
conserves the hydrogens and is consistent with a 1,2-hydride shift
mechanism wherein an enol is not formed. Furthermore, a double
entry
R
R
′
time (h)
% conversiona
A:B
1
2
3
4
5
6
7
8
9
Ph
H
H
H
H
H
H
H
24
48
32
16
24
48
24
48
48
>99 (75)
>99 (79)
>99 (83)
>99 (86)
95 (71)
>130:1
36:1
labeling experiment was performed with 18OH
and R-D-styrene.
2-methylphenyl
3-methylphenyl
4-methylphenyl
2,4,6-trimethylphenyl
3-chlorophenyl
3-nitrophenyl
Ph
2
22:1
22:1
The results of this experiment are similar to the individual labeling
studies and confirm two parallel pathways for decomposition that
are insensitive to the nature of the nucleophile.15 It is important to
note that a hydride shift mechanism need not proceed via Pd(0),
thus avoiding the common decomposition pathways associated with
related processes.
>150:1
>150:1
>150:1
>98 (80)
b
90 (79)
c
42:35d
Ph
Me
(42)
Ph
97e
2.3:1
Overall, we have discovered a Pd-catalyzed ligand-modulated
Wacker oxidation of styrene derivatives, including internal olefins,
using mild conditions with a simple oxidant. Isotopic labeling
experiments support a dominant pathway wherein TBHP acts as
the oxygen source in the addition to the olefin followed by a hydride
shift process wherein the protons on styrene are incorporated into
product. On the basis of these findings, we are currently considering
new approaches to Pd-catalyzed olefin functionalization reactions
that do not rely on â-hydride elimination processes.
a
b
Isolated yield in parentheses. Conditions: 2.25 mol % 2, 12 mol %,
c
AgOTf. Conditions: 0.3 M in PhMe, 1.25 mol % 2, 4 mol % AgOTf,
d
3
5-50 °C. Two benzaldehydes are formed per oxidative cleavage. e A is
a 53:47 mixture of carbonyl regioisomers measured vs internal standard.
Acknowledgment. This work was supported by the NIH
(NIGMS-GM63540). Pd salts were a gift from Johnson Matthey.
Atta Arif performed the X-ray crystallographic analysis. M.S.S.
thanks the Dreyfus foundation and Pfizer for their support.
Supporting Information Available: Catalyst optimization, experi-
mental procedures, and kinetic data (PDF, CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
References
Figure 2. X-ray crystal structure of Pd(IiPr)(OH2)3‚(OTf)2‚(H2O)2. Two
(1) (a) Smidt, J. Chem. Ind. 1962, 54-62. (b) Tsuji, J. Synthesis 1984, 5,
369-384. Acetophenone yield ) 63%. (c) For a recent review, see:
Takacs, J. M.; Jiang, X.-T. Curr. Org. Chem. 2003, 7, 369-396.
OTf counterions and two H2O molecules are excluded for clarity.
Scheme 1. Commonly Proposed Mechanistic Pathways for Olefin
Oxidation
(2) (a) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 33, 3400-3420. (b) Mueller,
J. A.; Goller, C. P.; Sigman, M. S. J. Am. Chem. Soc. 2004, 126, 9724-
9734.
(
3) (a) Nishimura, T.; Kakiuchi, N.; Onoue, T.; Ohe, K.; Uemura, S. J. Chem.
Soc., Perkin Trans. 1 2000, 12, 1915-1918. (b) ten Brink, G. J.; Arends,
I. W.; Papdogianakis, G.; Sheldon, R. A. Chem. Commun. 1998, 21, 2359-
2360.
(
4) For an example using ionic liquids at high pressure, see: (a) Namboodiri,
V. V.; Varma, R. S.; Sahle-Demessie, E.; Pillai, U. R. Green Chem. 2002,
4
, 170-173. Acetophenone yield ) 79%. Using surfactants, see: (b)
Alandis, N.; Rico-Lattes, I.; Lattes, A. New J. Chem. 1994, 18, 1147-
1149. Yield ) 83%. Using TBHP, see: (c) Sommovigo, M.; Alper, H. J.
Considering direct kinetic evidence for nucleopalladation is not
feasible, isotopic labeling studies were used to probe the nature of
the nucleophile and subsequent decomposition to acetophenone.
Two limiting mechanistic scenarios have been proposed for this
transformation: addition of water to the olefin followed by a
2 2
Mol. Catal. 1994, 88, 151-158. Yield ) 30%. Using H O and phase-
transfer catalysis, see: (d) Barak, G.; Sasson, Y. J. Chem. Soc., Chem.
Commun. 1987, 1266-1267. Yield ) 56%.
(
(
5) Uozumi, Y.; Kato, K.; Hayashi, T. J. Org. Chem. 1998, 63, 5071-5075.
6) In situ formation of cationic palladium with 1.5 mol % [Pd(IiPr)Cl
2
]
2
+
)
-
6
BF
2
mol % AgX, 0.3 M in MeOH at 55 °C, balloon pressure of O . X
â-hydride elimination-type process or the mechanism originally
4
, OTs, OTf leads to >99% conversion of styrene in 24 h via GC,
proposed by Mimoun,14 wherein formation of a palladacycle via
decreasing the induction to <2 h.
3
(7) Solvents screened include THF, DME, CH CN, DMF, 2-butanone, tBuOH,
insertion of the olefin into a peroxo-Pd species is followed by a
3
PhCF , and 2,2,5,5-tetramethyltetrahydrofuran.
1,2-hydride shift-type mechanism (Scheme 1). The palladacycle
2
(8) H O2(aq) as a peroxide source resulted in poor product selectivity and high
levels of Pd decomposition.
mechanistic scenario has been used to account for the observed
formation of oxidatively cleaved products in the Wacker oxidation
(
9) Internal olefins often cannot be oxidized under standard PdCl
2 2
/CuCl
Wacker conditions (see ref 1).
4c
(10) Similar ratios of methyl ketone to oxidative cleavage are seen for styrene
under these conditions.
of styrenes. Previous isotopic labeling studies of ethylene oxidation
under classic Wacker conditions also support Mimoun’s 1,2-hydride
shift proposal.1
(
11) To avoid catalyst decomposition, >3 equiv of TBHP are necessary.
a
(12) Sharpless, K. B.; Verhoeven, T. R. Aldrichimica Acta 1979, 12, 63-71.
-1
0
0
(
(
2
13) Rate ) kobs[catalyst][H O] [substrate] [TBHP] .
To determine if TBHP or H
2
O is the oxygen source in the
14) (a) Mimoun, H.; Charpentier, R.; Mitschler, A.; Fischer, J.; Weiss, R. J.
Am. Chem. Soc. 1980, 102, 1047-1054. (b) Roussel, M.; Mimoun, H. J.
Org. Chem. 1980, 45, 5387-5390.
carbonyl, the Wacker oxidation of styrene using 1.1 equiv of
1
8
OH
2
under otherwise anhydrous conditions was examined. Only
0% 18O incorporation at 15 m (1.3% product) is observed, which
(15) See Supporting Information for details.
2
is consistent with TBHP as the primary oxygen source in aceto-
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J. AM. CHEM. SOC.
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