Convenient and efficient Pd-catalyzed regioselective oxyfunctionalization of terminal olefins by using molecular oxygen as sole reoxidant

Article abstract of DOI:10.1002/anie.200502886

(Chemical Equation Presented) Just the one: The combination of palladium dichloride and N,N-dimethylacetamide (DMA) constitutes a highly efficient and reusable catalytic system, which uses molecular oxygen as the sole reoxidant for liquid-phase Wacker oxidation and acetoxylation of terminal olefins to the corresponding methyl ketones and linear allylic acetates, respectively (see scheme). 2006 Wiley-VCH Verlag GmbH Co. KGaA.

Full text of DOI:10.1002/anie.200502886

Angewandte
Chemie
Synthetic Methods
DOI: 10.1002/anie.200502886
Convenient and Efficient Pd-Catalyzed
Regioselective Oxyfunctionalization of Terminal
Olefins by Using Molecular Oxygen as Sole
Reoxidant**
Takato Mitsudome, Takuya Umetani, Naoya Nosaka,
Kohsuke Mori, Tomoo Mizugaki, Kohki Ebitani, and
Kiyotomi Kaneda*
The evolution of selective oxidation routes that use molecular
oxygen (O2) is one of the ultimate goals of present-day
chemical research.[1] In particular,the Pd-catalyzed Wacker
oxidation and acetoxylation of terminal olefins have received
[*] T. Mitsudome, T. Umetani, N. Nosaka, Dr. K. Mori, Dr. T. Mizugaki,
K. Ebitani, Prof. K. Kaneda
Graduate School of Engineering Science
Osaka University, 1-3 Machikaneyama
Toyonaka, Osaka 560-8531 (Japan)
Fax: (+81)6-6850-6260
E-mail: kaneda@cheng.es.osaka-u.ac.jp
[**] This investigation was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan (16206078). We thank the centerof
excellence (21COE; program “Creation of Integrated Ecochemistry”,
Osaka University) and Dr. Uruga (Spring-8) for X-ray absorption
fine-structure (XAFS) measurements.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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[a]
Table 1: Wackeroxidation of 1-decene undervairous conditions,
and
much attention because of useful protocols for direct oxy-
functionalization at the C1 and C2 positions.[2] These pro-
cesses,however,require cocatalysts,such as copper, [3] hetero-
polyacids,[4] or benzoquinone,[5] or reducing agents[6] to
facilitate the reoxidation of the Pd0 species by O2 and prevent
its precipitation into inactive metals. Current research has
focused on the development of promising methodologies that
do not rely on these cocatalysts because of practical and
environmental concerns.[7] However,few examples of oxy-
functionalization systems using O2 as the sole reoxidant have
appeared,and these Pd-catalyzed oxidation reactions often
suffer from low activities and a limited substrate scope.[8,9] We
disclose that PdCl2 in combination with DMA as the solvent is
an extremely simple and highly efficient catalytic system for
the Wacker oxidation of terminal olefins. This catalytic system
allows for an efficient dioxygen-coupled turnover without the
need for additional cocatalysts or reducing reagents; it is
tolerant toward long-chain and functionalized olefins and is
also applicable to Wacker-type intramolecular cyclization.
Furthermore,it facilitates acetoxylation of the terminal
olefins,thus affording selectively linear allylic acetates. An
oxygen atom can be selectively incorporated at the C1 or C2
position of terminal olefins by using an appropriate nucleo-
phile,namely,H 2O or AcOH (Scheme 1). The work-up
procedure is also straightforward,and the solution containing
the catalyst can be recycled without any loss of activity and
selectivity.
the peak potentials forreduction ( Ered) and oxidation (Eox) obtained by
cyclic voltammetry.
Entry Catalyst
Solvent Yield [%][b] Ered [V vs.
Eox [V vs.
SCE]
SCE]
1
PdCl2
DMA
NMP
DMPA
DMF
EtOH trace
MeCN trace
84
74
33
À0.70
À0.69
À0.57
À0.50
À0.10
À0.40
–
À0.26
À0.20
À0.13
À0.12
0.19
0.10
–
2
PdCl2
3
PdCl2
4
PdCl2
trace
5
PdCl2
6
PdCl2
7
Pd(OAc)2
DMA
trace
trace
8
[PdCl2(NH3)4] DMA
PdCl2 DMA
–
–
–
9[c]
85 (83)
–
[a] Reaction conditions: 1-decene (0.5 mmol), Pd catalyst (0.005 mmol),
solvent (5 mL), H2O (0.3 mL), 1 atm of O2, 6 h, 808C. [b] Values in
parenthesis are yields of the isolated product. [c] 1-Decene (20 mmol),
PdCl2 (0.1 mmol), DMA (60 mL), H2O (10 mL), 10 atm of O2, 10 h.
SCE=saturated calomel electrode, NMP=N-methylpyrrolidone, DMA=
N,N-diemthylacetamide, DMPA=N,N-dimethylpropionamide.
with cocatalysts,such as PdSO 4/per(2,6-di-o-methyl)-b-cyclo-
dextrin/H9PV6Mo6O40/CuSO4 (TOF and TON: 7.7 hÀ1 and
46),[4a] Pd(OAc)2/carbon/molybdovanadophosphate/NH4Cl/
MeSO4 (TOF and TON: 3.3 hÀ1 and 16),[4b] PdCl2/a-cyclo-
dextrin/CuCl2 (1.9 hÀ1 and 19),[3e] and PdCl2/b-cyclodextrin/
CuCl2 (0.3 hÀ1 and 15).[3d]
Awide range of terminal olefins were oxidized to form the
corresponding methyl ketones in high yields (Table 2).[11] For
example,the oxidation of long-chain olefins 1-hexadecene
and 1-eicosene occurred efficiently to give the ketones in 85
and 81% yields,respectively (Table 2,entries 5 and 6). In
Scheme 1. Selectively incorporation of an oxygen atom at the C1 or C2
position of terminal olefins.
contrast,oxidation of 1-eicosene with PdCl /CuCl2 in poly-
2
ethyleneglycol[3c] and Pd(OAc)2/hydroquinone/Fe(phthalo-
cyanine) in DMF[5] resulted in less than 10% yields of 2-
eicosenone. In the case of 1,7-octadiene, the use of the PdCl2–
DMA catalytic system afforded the corresponding diketone
in 81% yield (Table 2,entry 7). The system was also found to
be applicable to the oxidation of functionalized terminal
olefins possessing cyano and hydroxyl groups. 5-Hexeneni-
trile and 9-octene-1-ol afforded the corresponding ketones
selectively,with suppression of hydration and alcohol oxida-
tion (Table 2,entries 9 and 10).
The reaction conditions were optimized for the Wacker
oxidation of 1-decene (1a) using various Pd complexes and
solvents under an atmospheric pressure of O2 (Table 1). The
combination of PdCl2 and DMA exhibited the highest
catalytic activity,thus affording 2-decanone ( 2a) in 84%
yield after 6 h without formation of olefinic isomers (Table 1,
entry 1).[10] No Pd precipitation was observed during the
ii
above reaction,and the retention of monomeric Pd species
was confirmed after the reaction by Pd K-edge X-ray
absorption fine-structure (XAFS) spectroscopic analysis.[11]
The use of NMP and DMPA in place of DMA gave moderate
yields (Table 1,entries 2 and 3),whereas dimethylformamide
(DMF),ethanol,and acetonitrile were significantly less
effective (Table 1,entries 4–6). The choice of Pd source was
found to influence catalytic efficiency: only PdCl2 could
function as a catalyst (Table 1,entry 1 vs. entries 7 and 8).
Compound 1a (20 mmol,2.8 g) was successfully converted
into 2a (83% yield of isolated product,2.6 g) with a turnover
frequency (TOF) of 17 hÀ1 and a turnover number (TON) of
up to 170 (Table 1,entry 9). These values are considerably
greater than those reported for other catalytic systems of Pd
A further advantage of this catalytic system is the facile
separation of the oxidized products from the reaction
mixture. Addition of n-heptane to the reaction mixture
upon completion of the reaction followed by decantation of
the n-heptane phase containing the oxidized products allows
the active Pd species in the residual DMA solution to be
recycled. We conducted further oxidations by the addition of
successive portions of the olefin to the Pd–DMA phase
followed by stirring under identical reaction conditions. The
second and third oxidation cycles of 1a proceeded at rates
similar to that of the original reaction,thus affording 2a in
yields of more than 80% with 99% selectivity. The total TON
reached 250 after the third recycling process. This separation
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Chemie
Table 2: Wackeroxidation of various olefins catalyzed by the PdCl 2–DMA system.[a]
with 93% selectivity,accompanied
by a 6% yield of branched allylic
acetate,without the formation of
olefinic isomers or Wacker prod-
ucts (Table 3,entry 1). Both the
activity and regioselectivity of the
acetoxylation are significantly
superior to those reported for a
Entry
Substrate
t [h]
Conv. [%]
Product
Yield [%][b]
82 (78)
1
2
3
85
82
3
81 (75)
3
3
86
85 (83)
Pd(OAc)2–dimethyl
sulfoxide
4[c]
5[c]
6[c]
3
3
3
88
88
82
88 (85)
85 (82)
81 (76)
(DMSO) system,which required a
large amount of benzoquinone as a
redox reagent.[14,15] To the best of
our knowledge,this is the first
demonstration of a cocatalyst-free
regioselective acetoxylation of ter-
minal olefins to linear allylic ace-
tates using O2 as a terminal oxi-
dant.
7[d]
40
100
81 (78)
19
As well as long-chain aliphatic
olefins,acetoxylation proceeded
efficiently to give the correspond-
ing linear allylic acetates,even for
those olefins with sensitive func-
tional groups,such as ester,nitrile,
and acetal groups (Table 3,
entries 2–8). This method is a pow-
erful candidate for the a-oxyfunc-
tionalization of versatile terminal
olefins,such as hydroboration–oxi-
dation[16] and oxidation using
chromyl chloride.[17]
Cyclic-voltammetric analysis of
PdCl2 in various solvents was car-
ried out to elucidate the positive
effect of DMA on the Wacker
oxidation. These spectra showed
single irreversible reduction and
8[d]
9[d]
40
40
24
97
84
89
96 (92)
80 (75)
89 (85)
10[d]
11[d]
3
86
74 (66)
12[d]
13[d]
24
40
96
94
91 (88)
87 (85)
[a] Reaction conditions: substrate (1 mmol), PdCl2 (0.005 mmol), DMA (3 mL), H2O (0.5 mL), 6 atm of
O2, 808C. [b] Yields were determined by GC analysis; values in parenthesis are the yields of the isolated
products. [c] DMA (5 mL). [d] Substrate (0.5 mmol). Conv.=conversion
method is strikingly simple in comparison to the previously
reported methods using fluoro solvents[12] and ionic liquids.[13]
This catalytic system was also found to be applicable to
Wacker-type intramolecular cyclizations,even in the presence
of a catalytic amount of sodium acetate.[9] 2-Allylphenol and
2-cyclopentene-1-acetic acid were smoothly converted into 2-
methylbenzofuran and 3,3a,4,6a-tetrahydro-2H-cyclopen-
ta[b]furan-2-one,respectively,in high yields (Scheme 2).
When AcOH is used as a nucleophile instead of H2O,
regioselective acetoxylation of terminal olefins to the corre-
sponding linear allylic acetates takes place without the use of
a cocatalyst (Table 3). For example, 1a predominantly under-
went acetoxylation to provide 2-decenyl ester in 80% yield
oxidation peaks: the oxidation peak of the electrogenerated
Pd0 species appeared at a more negative potential value in
DMA (Eox = À0.26 V) than in other solvents (Table 1,
entries 1–6). Interestingly,yields of 2a increase with increas-
ing negative Eox values of DMA,NMP,and DMPA (Table 1,
entries 1–3),which supports the contention that DMA acts as
the most efficient solvent for promoting the reoxidation of the
Pd0 species.[11,18] In a separate experiment,XAFS analysis
showed that Pd sponge was readily oxidized to a homoge-
neous Pdii species in a solution of DMA in the presence of two
equivalents of HCl under atmospheric O2 at 808C.[11] Wacker
oxidation proceeded to afford 2a in 76% yield in 8 h upon
addition of 1a to this solution of Pd. Kinetic studies revealed
that the initial reaction rate of 1a (R0) was dependent on O2
pressure (pO2) and the concentration of the catalyst ([Pd])
+
.
and independent of the concentration of 1a, H2O,and H
Taking into account the mechanism proposed by Stahl and co-
workers for Pd-catalyzed aerobic oxidation,we propose a
possible reaction cycle for the present Wacker oxidation in
which the rate-determining reoxidation step of Pd0 kcat
competes with its decomposition into inactive Pd0 metal kdec
(Scheme 3).[19] The R0 value for the Wacker oxidation of 1a
Scheme 2. Intramolecular Wacker-type cyclization by PdCl2 in DMA.
Angew. Chem. Int. Ed. 2006, 45, 481 –485
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Communications
Table 3: Acetoxylation of various olefins by PdCl2 using molecularoxygen. [a]
Keywords: acetoxylation · alkenes · oxygen ·
palladium · Wackeroxidation
.
Entry Substrate
Conv. [%] Major product
Linear/
E/Z[c]
Yield [%][d]
branched[b]
1
86
93
65
13:1
10:1
10:1
7:1
1:1
2:1
6:1
86 (85)
90 (82)
43 (40)
20 (18)[f]
2
3[e]
[1] a) R. A. Sheldon,J. K. Kochi, Metal-Cata-
lyzed Oxidations of Organic Compounds,
Academic Press,New York, 1981; b) M.
Hudlucky, Oxidations in Organic Chemistry,
American Chemical Society,Washington,
DC, 1990 (ACS Monograph Series); c) P. T.
Anastas,L. B. Bartlett,M. M. Kirchhoff,
T. C. Williamson, Catal. Today 2000, 55,11;
d) Modern Oxidation Methods (Ed.: J. E.
Bäckvall),Wiley-VCH,Weinheim, 2004.
[2] a) B. Škermark,K. Zetterberg, Handbook
of Organopalladium Chemistry for Organic
Synthesis, Vol. 2 (Ed.: E. Negishi),Wiley,
New York, 2002,p. 1875; b) P. M. Henry,
Handbook of Organopalladium Chemistry
for Organic Synthesis, Vol. 2 (Ed.: E.
4[e]
5[e]
95
85
8:1
9:1
8:1
90 (85)
80 (76)
10:1
6[e]
7[e]
8
56
85
85
45:1
20:1
17:1
–
56 (50)[g]
>99:1 79 (75)
>99:1 85 (84)
[a] Reaction conditions: substrate (1 mmol), PdCl2 (0.01 mmol), NaOAc (0.2 mmol), 4-ꢀ molecular
Negishi),Wiley,New York,
2002,p. 2119;
sieves (0.2 g), DMA (5 mL), AcOH (0.2 mL), 6 atm of O2, 40 h, 808C. [b] Ratio based on GC analysis of
c) T. Hosokawa,S.-I. Murahashi, Handbook
of Organopalladium Chemistry for Organic
Synthesis, Vol. 2 (Ed.: E. Negishi),Wiley,
New York, 2002,p. 2141; d) M. Takacs,X.-T.
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Tsuji, Palladium Reagents and Catalysts,
Wiley,Chichester, 2004; f) M. Beller,J.
Seayad,A. Tillack,H. Jiao, Angew. Chem.
1
crude product. [c] Ratio based on H NMR spectroscopic analysis of the crude product. [d] Yields of
linear+branched allylic acetates were determined by GC analysis; values in parenthesis are yields of the
isolated products. [e] Substrate (0.5 mmol). [f] (E,E)/(E,Z)/(Z,Z)=15:4:1. [g] Mixture of 1-cyclohexene
ethanol acetate/2-cyclohexylidene ethanol acetate (1:1).
2004, 116,3448; Angew. Chem. Int. Ed. 2004, 43,3368.
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Scheme 3. Proposed catalytic cycle. kcat =rate of the reoxidation step,
dec =rate of the decomposition.
k
can be expressed as follows: R0 = kcat pO2 [Pd]t,[Pd]
=
t
[Pd]0/(1+[Pd]0 kdec t) (the values of kcat and kdec at 808C in
DMA were determined to be 0.02 and 1.81mÀ1 sÀ1,respec-
tively). The value of kcat/kdec was almost 2.3 times greater than
that observed in DMF.[11] These observations clearly show
that DMA promotes the reoxidation of the Pd0 species by O2
and simultaneously suppresses competing Pd0 aggregation. It
can be said that the use of DMA results in a unique catalytic
system capable of performing the Wacker oxidation in the
absence of a cocatalyst. With respect to the above acetox-
ylation,DMA might accelerate the reoxidation of Pd 0 species
by O2.
In conclusion,the combination of PdCl 2 and DMA allows
highly effective oxygenation of terminal olefins under coca-
talyst-free conditions. The use of a different nucleophile (H2O
or AcOH) can lead to a complete switch in regioselectivity
between the C1 and C2 positions. The versatility demon-
strated by this simple catalytic system holds significant
promise for achieving new oxidation system using O2 as a
sole reoxidant.
[6] The Wacker oxidation using O2 with propan-2-ol as a reducing
reagent: a) T. Nishimura,N. Kakiuchi,T. Onoue,K. Ohe,S.
Uemura, J. Chem. Soc. Perkin Trans. 1 2000, 12,1915; with THF
as a cosolvent; b) C. N. Cornell,M. S. Sigman, J. Am. Chem. Soc.
2005, 127,2796.
[7] S. S. Stahl, Angew. Chem. 2004, 116,3480; Angew. Chem. Int. Ed.
2004, 43,3400.
[8] Examples of Pd-catalyzed Wacker oxidations using O2 as a sole
reoxidant without cocatalyst: a) M. Higuchi,S. Yamaguchi,T.
Hirao, Synlett 1996,1213; b) G.-J. ten Brink,I. W. C. E. Arends,
G. Papadogianakis,R. A. Sheldon, Chem. Commun. 1998,2359.
[9] Examples of Pd-catalyzed Wacker-type intramolecular cycliza-
tions using molecular oxygen as a sole reoxidant without a
cocatalyst: a) H. Hiemstra,J. J. Michels,W. N. Speckamp,
J.
Chem. Soc. Chem. Commun. 1994,357; b) R. M. Trend,Y. K.
Ramtohul,E. M. Ferreira,B. M. Stoltz, Angew. Chem. 2003, 115,
2998; Angew. Chem. Int. Ed. 2003, 42,2892; c) K. Muꢀiz, Adv.
Synth. Catal. 2004, 346,1425; d) G. Zeni,R. C. Larock, Chem.
Rev. 2004, 104,2285.
Received: August 13,2005
Published online: December 2,2005
[10] In our experiment,the Pd(OAc) 2–DMSO system,which was
effective for an intramolecular Wacker-type cyclization and
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Chemie
acetoxylation,failed to promote the Wacker oxidation of 1-
decene (< 1% yield in 6 h).
[11] See the Supporting Information for the experimental details.
[12] For example,see: I. Horvath,J. Rabai, Science 1994, 266,72.
[13] T. Welton, Chem. Rev. 1999, 99,2071.
[14] There has been only one report of the selective synthesis of
linear allylic acetates from terminal olefins: M. S. Chen,M. C.
White, J. Am. Chem. Soc. 2004, 126,1346; however,we
confirmed that the acetoxylation of 1-eicosene hardly occurred
with the above catalytic system.
[15] Selective synthesis of branched allylic acetates from terminal
olefins: M. S. Chen,N. Prabagaran,N. A. Labenz,M. C. White, J.
Am. Chem. Soc. 2005, 127,6970.
[16] R. C. Larock, Comprehensive Organic Transformations,2nd ed,
Wiley,New York, 1999.
[17] F. Freeman,P. J. Cameron,R. H. Dubois, J. Org. Chem. 1968, 33,
3970.
[18] J. Pytkowicz,S. Roland,P. Mangeney,G. Meyer,A. Jutand,
J.
Organomet. Chem. 2003, 678,166.
[19] B. A. Steinhoff,S. R. Fix,S. S. Stahl, J. Am. Chem. Soc. 2002, 124,
766.
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