Efficient diacetoxylation of alkenes via Pd(II)/Pd(IV) process with peracetic acid and acetic anhydride

Article abstract of DOI:10.1021/ol1001686

A palladium-catalyzed diacetoxylation of alkenes in the presence of peracetic acid and acetic anhydride was developed to produce diacetates efficiently and diastereoselectively. Due to its mild conditions, this method was suitable for a broad range of substrates encompassing conjugated and nonconjugated olefins.

Full text of DOI:10.1021/ol1001686

ORGANIC
LETTERS
2010
Vol. 12, No. 11
2450-2452
Efficient Diacetoxylation of Alkenes via
Pd(II)/Pd(IV) Process with Peracetic Acid
and Acetic Anhydride
Chan Pil Park, Joo Ho Lee, Kyung Soo Yoo, and Kyung Woon Jung*
Loker Hydrocarbon Research Institutute and Department of Chemistry, UniVersity of
Southern California, Los Angeles, California 90089-1661
kwjung@usc.edu
Received February 12, 2010
ABSTRACT
A palladium-catalyzed diacetoxylation of alkenes in the presence of peracetic acid and acetic anhydride was developed to produce diacetates
efficiently and diastereoselectively. Due to its mild conditions, this method was suitable for a broad range of substrates encompassing conjugated
and nonconjugated olefins.
The Pd-catalyzed dioxygenation of alkenes is an important
difunctionalization method in organic synthesis due to its
efficiency, safety, and economy,1 although osmium catalysts
have been widely used for dioxygenation reactions.2 Sigman
proposed a Pd(II)-catalyzed aerobic dialkoxylation of styrene
derivatives requiring an o-phenol to facilitate the formation
of a quinone methide intermediate.1b On the other hand, we
envisioned an alternative Pd(II)/Pd(IV) mechanism for di-
oxygenation and embarked on the development of efficient
processes for alkene diacetoxylation via peracetic acid as
an oxidant. During the course of our research, Dong3a and
Jiang3b reported olefin diacetoxylation catalyzed by pal-
ladium complexes in the presence of either PhI(OAc)2 or
molecular oxygen as an oxidant (eqs 1 and 2).
These olefin dioxygenations would presumably occur by
a distinct Pd(II) to Pd(IV) process, which is significantly
broad in its application toward various alkenes.4 However,
the use of PhI(OAc)2 as a stoichiometric oxidant produces a
large amount of byproduct, while the use of molecular oxygen
as an oxidant requires high pressure, temperature, and long
reaction time. Therefore, our newly developed Pd(II)/Pd(IV)
processes using peracetic acid can provide practical improve-
ments over the previously reported reaction conditions.
(1) (a) Chevrin, C.; Le Bras, J.; Henin, F.; Muzart, J. Synthesis 2005,
2615–28618. (b) Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006,
128, 1460–1463. (c) Thiery, E.; Chevrin, C.; Le Bras, J.; Harakat, D.;
Muzart, J. J. Org. Chem. 2007, 72, 1859–1862. (d) Zhang, Y.; Sigman,
M. S. J. Am. Chem. Soc. 2007, 129, 3076–3077. (e) Jensen, K. H.; Sigman,
M. S. Org. Biomol. Chem. 2008, 6, 4083–4088.
(2) (a) Finn, M. G.; Sharpless, K. B. J. Am. Chem. Soc. 1991, 113, 113–
126. (b) Crispino, G. A.; Ho, P. T.; Sharpless, K. B. Science 1993, 259,
64–66. (c) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
ReV. 1994, 94, 2483–2547. (d) Kobayashi, S.; Endo, M.; Nagayama, S.
J. Am. Chem. Soc. 1999, 121, 11229–11230. (e) Donohoe, T. J.; Blades,
K.; Winter, J. J G.; Stemp, G. Tetrahedron Lett. 2000, 41, 4701–4704. (f)
Donohoe, T. J. Synlett 2002, 8, 1223–1232. (g) Donohoe, T. J.; Harris,
R. M.; Butterworth, S.; Burrows, J. N.; Cowley, A.; Parker, J. S. J. Org.
Chem. 2006, 71, 4481–4489. (h) Christie, S. D. R.; Warrington, A. D.
Synthesis 2008, 1325–1341.
Our initial studies included the identification of appropriate
conditions and the understanding of the possible mechanism
(3) (a) Li, Y.; Song, D.; Dong, V. M. J. Am. Chem. Soc. 2008, 130,
2962–2964. (b) Wang, A.; Jiang, H.; Chen, H. J. Am. Chem. Soc. 2009,
131, 3846–3847.
(4) (a) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004,
126, 2300–2301. (b) Desai, L. V.; Sanford, M. S. Angew. Chem., Int. Ed.
2007, 46, 5737–5740.
10.1021/ol1001686  2010 American Chemical Society
Published on Web 05/10/2010

for the oxygenation using a palladium catalyst. As repre-
sentatively shown in Scheme 1, diacetoxylation was facile
to give hydroxyacetoxylation product (4) preferably along
with small amounts of diacetate 2. Upon the addition of acetic
anhydride, the chemoselectivity for the diacetoxylation
product (2) improved significantly (entries 3-6), and its yield
was proportional to the amount of acetic anhydride. Optimal
results were obtained when styrene was added to the
premixed solution of AcO2H and Ac2O at 0 °C and the
reaction mixture was slowly warmed to room temperature
(see the Supporting Informaiton).
Scheme 1
On the basis of these results, it can be suggested that
Pd(OAc)2 could be oxidized to Pd(IV)(OH)(OAc)3 without
acetic anhydride or Pd(IV)(OAc)4 with acetic anhydride.
Keeping in mind this possibility, we propose a mechanism
for the diacetoxylation of an alkene (Figure 1). The Pd(IV)
in the presence of a combination of peracetic acid and acetic
anhydride with palladium acetate, converting styrene (1) to
diacetate 2 at room temperature efficiently. To validate the
possibility of Pd(II)/ Pd(IV) process, we compared similar
conditions without peracetic acid or acetic anhydride. When
the reaction was carried out with only acetic acid, styrene
underwent acetoxylation and ꢀ-hydride elimination to furnish
the vinyl acetate 3 presumably via a Pd(0)/Pd(II) process.
However, when the reaction was performed in the presence
of peracetic acid as the oxidant at an ambient temperature,
hydroxyacetoxylated products (4) were produced, implying
a Pd(II)/Pd(IV) process instead of Pd(0)/Pd(II). In addition,
when acetic anhydride was added to the mixture of 4 under
similar conditions, conversion of 4 to 2 was not observed
by 1H NMR spectra. Therefore, diacetoxylation would require
both peracetic acid and acetic anhydride, and further
investigation was carried out.
Figure 1. Plausible Pd(II)/Pd(IV) pathway.
species II (palladium tetraacetate), generated from Pd(OAc)2
and peracetic acid/acetic anhydride, is suggested to be the
starting point of alkene acetoxylaion.5 The highly reactive
Pd(IV) species would then undergo syn-addition onto the
alkene to generate palladium intermediate IV, while
maintaining the Pd(IV) oxidation state. This is followed
quickly by reductive elimination to afford the diacetoxy-
lation product from Pd(IV) center and regenerate
Pd(OAc)2. The most notable feature of the proposed
catalysis is its ability to facilitate diacetoxylation under
mild conditions such as ambient temperature and a short
reaction time.
As shown in Table 1, we examined the correlation between
product selectivity and the ratio of peracetic acid and acetic
a
Table 1. Diacetoxylation of Styrene with Pd(OAc)2
Next, we screened various olefins using the optimal
conditions. First, we examined 3-butenoic acid as a repre-
sentative nonconjugated olefin to afford diacetate product
6, which was anticipated to cyclize to the valuable lactone
7.6 In the absence of palladium catalysts, only a trace amount
of lactone compound was observed, and most of the
unreacted 3-butenoic acid was recovered (Table 2, entry 1).
conversionc (%)
entry time (h) AcO2Hb (mmol) Ac2O (mmol)
1
4
2
1
2
3
4
5
6
4
4
4
4
4
4
0.13
0.26
0.26
0.26
0.26
0.26
0
0
1.3
2.6
5.2
7.8
41
12
4
0
0
53
78
79
62
21
6
6
10
17
38
79
94
(5) (a) Nagata, R.; Saito, I. Synlett 1990, 291–301. (b) Chen, M. J. Y.;
Kochi, J. K. J. Chem. Soc., Chem. Commun. 1977, 204–205. (c) Muzart, J.
J. Mol. Catal. A: Chemical 2007, 276, 62–72.
0
a All reactions were carried out with styrene (0.26 mmol) and Pd(OAc)2
(0.026 mmol) in acetic acid (500 µL). b 35.5 wt % in AcOH. c The conversions
were determined by 1H NMR in the presence of an internal standard.
(6) (a) Ahmed, M. M.; Berry, B. P.; Hunters, T. J.; Tomcik, D. J.;
O’Doherty, G. A. Org. Lett. 2005, 7, 745–748. (b) Wu, Y.; Guan, M. Indian
J. Chem., Sec. B: Org. Chem. Med. Chem. 1998, 37B, 844–846. (c)
Brzezinski, L. J.; Rafel, S.; Leahy, J. W. J. Am. Chem. Soc. 1997, 119,
4317–4318. (d) Tiecco, M.; Testaferri, L.; Tingoli, M. Tetrahedron 1993,
49, 5351–5358. (e) Uchiyama, H.; Kobayashi, Y.; Sato, F. Chem. Lett. 1985,
467–470.
anhydride. In the presence of only peracetic acid as an
oxidant (entries 1 and 2), dioxygenation of styrene proceeded
Org. Lett., Vol. 12, No. 11, 2010
2451

Table 2. Pd-Catalyzed Diacetoxylation of 3-Butenoic acid.a
Table 3. Pd-Catalyzed Diacetoxylation of Alkenesa
entry catalyst
oxidant
solventb
AcOH
AcOH
AcOH
time (h) yieldc (%)
1
none
AcO2H
AcO2H
12
8
trace
10
2
PdCl2
3
Pd(OAc)2 AcO2H
4
72
4
Pd(OAc)2 PhI(OAc)2 AcOH
12
4
4
trace
62
92
5d
6e
Pd(OAc)2 AcO2H
AcOH/MeCN
Pd(OAc)2 AcO2H
AcOH
a 1.0 mmol scale (0.1 M solution), 5 mol % of Pd catalyst, and 1.2
equiv of oxidant, yield by 1H NMR data spectra using an internal standard.
b In entries 1-5, H2O was evaporated to afford the cyclized product after
reaction. c Isolated yields. d AcOH/MeCN ) 1:1 (wt %). e Anhydrous acetic
acid.
When PdCl2 effected the oxidation to a small degree (entry
2), Pd(OAc)2 facilitated the oxidation and cyclization to offer
lactone 7 in a good yield (entry 3). Other oxidants such as
PhI(OAc)2 were also tested, but none of them afforded
significant efficiency (entry 4).7 By varying solvents, we
sought optimal conditions. Wet acetic acid (entry 3) and
organic solvents (entry 5) were not comparable to the use
of anhydrous acetic acid (entry 6), which converted 3-buteno-
ic acid completely to the desired lactone 7 in an excellent
yield.
Using the developed reaction conditions, we extended the
diacetoxylation protocol to a number of olefins to verify the
generality of this method. As shown in Table 3, the desired
reaction products were synthesized generally in high yields.
Terminal aliphatic olefins including 3-butenenitrile, 3-methyl-
3-butenyl acetate, and allylbenzene afforded their corre-
sponding diacetoxylation products 8, 9, and 10, respectively,
in 93%, 90%, and 86% yields (entries 1-3). In the case of
the trisubstituted cyclic alkene, 1-methyl-1-cyclohexene
underwent diacetoxylation smoothly to give the desired
diacetate product 11 in 89% yield along with high diaste-
reoselectivity (syn/anti ) 15/1) (entry 4). Disubstituted
aromatic alkenes also provided the desired vicinal oxygen-
ation products (entries 5-7), and the high syn-addition of
acetoxy group was confirmed again (entries 6 and 7) (syn/
anti ) 10/1, 12/1, respectively).3a Furthermore, the reaction
with 1-phenyl-1-cyclohexene as a trisubstituted conjugated
olefin took place efficiently to provide the desired compound
15 in 87% yield along with high diastereoselectivity (syn/
anti ) 15/1) (entry 8).
a 1.0 mmol scale (0.1 M solution), 2 mol % of Pd(OAc)2, and 1.2 equiv
of CH3CO3H. b Isolated yields. c The diastereomeric ratios were determined
by H NMR analysis. d Reaction temperature was 45 °C.
1
under ambient temperature and pressure. Mono- to trisub-
stitued alkenes were compatible with the developed method.
In addition, high stereoselectivity as well as functional group
tolerance is worthy of note. Overall, our processes are
believed to provide a convenient and practical method.
Acknowledgment. We acknowledge generous financial
support from the National Institutes of Health (Grant Nos.
RO1 GM 71495 and S10 RR025432).
In conclusion, we have successfully developed a highly
reactive palladium-catalyzed diacetoxylation for a broad
range of alkenes, including conjugated and nonconjugated,
Supporting Information Available: Experimental details
for the prepararion of compounds and spectral data of these
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(7) In Song’s report (ref 3a), use of excess PhI(OAc)2 improved the
yield and reduced ꢀ-hydride elimination.
OL1001686
2452
Org. Lett., Vol. 12, No. 11, 2010