Palladium-catalyzed olefin dioxygenation

Article abstract of DOI:10.1021/ja711029u

A general method for the vicinal dioxygenation of olefins was developed using cationic Pd diphosphine complexes as the catalysts and PhI(OAc)₂ as the terminal oxidant. In comparison to known Pd-catalyzed vicinal oxidations, this method is suitable for a broad range of olefins in both inter- and intramolecular reactions. An ¹⁸O-labeling experiment provides insight into the mechanism of this transformation which presumably involves Pd(II)/Pd(IV) intermediates. Copyright

Full text of DOI:10.1021/ja711029u

Published on Web 02/19/2008
Palladium-Catalyzed Olefin Dioxygenation
Yang Li, Datong Song,* and Vy M. Dong*
DaVenport Chemical Research Laboratories, Department of Chemistry, UniVersity of Toronto,
80 St. George Street, Toronto, Ontario, M5S 3H6, CANADA
Received December 18, 2007; E-mail: dsong@chem.utoronto.ca; vdong@chem.utoronto.ca
Table 1. Pd-Catalyzed Oxidation of trans-Stilbene with
Hypervalent Iodine
Palladium-catalyzed vicinal oxidation has emerged as an attrac-
tive approach for making valuable products from simple and readily
available olefins.1-4 For example, diamination1b and aminooxy-
genation2 of olefins have been achieved based on the Pd(II)/Pd-
(IV) catalyst cycle, a mechanistic design that has garnered
significant attention as a result of Sanford’s efforts.5 Despite the
prevalence of 1,2-dioxygenated motifs in various organic architec-
tures, a corresponding Pd(II)/Pd(IV) dioxygenation of alkenes has
not previously been realized. Herein, we report a novel olefin
dioxygenation catalyzed by cationic palladium diphosphine com-
plexes. In comparison to related Pd-based methods, this olefin
difunctionalization presumably occurs by a distinct Pd(II)/Pd(IV)
mechanism and is significantly broad in scope, not limited to
terminal olefins and/or alkenes bearing a directing group. Due to
the low cost and toxicity of Pd salts relative to Os complexes, this
strategy also represents a promising compliment to the well-known
Sharpless dihydroxylation (Scheme 1).
entry
catalyst
mol %
time (h)
yield (%)a,b
(syn:anti)c
1
2
3
4
5
6
7
none
Pd(OAc)2
PdCl2(MeCN)2
Pd(bpy)(OAc)2
Pd(BINAP)(OAc)2
Pd(BINAP)(TFA)2
[Pd(dppp)(H2O)2](OTf)2
none
16
16
16
16
16
16
2
0
0
0
5
5
5
5
5
2
0
24
46
72
5:1
6:1
6:1
4
a 0.25 mmol scale (0.1 M in HOAc), 1.1 equiv of PhI(OAc)2 and 3.0
equiv of H2O. b Yield by 1H NMR using internal standard. c Determined
1
by H NMR integration.
Scheme 1. Proposed Pd(II)/Pd(IV) Compliment to Os(VIII)/Os(VI)
Catalytic Dioxygenation of Alkenes
Table 2. Results of Isotopic Labeling Study with 18O-Enriched
Water
isotopic mix-3a
m/za
abundance (%)b
Our initial studies focused on identifying a palladium species
capable of catalyzing the desired vicinal oxygenation of trans-
stilbene (1) with hypervalent iodine 2 as the terminal oxidant, in
wet acetic acid (eq 1). No background oxidation was observed
(Table 1, entry 1). Furthermore, Pd(OAc)2 and PdCl2(CH3CN)2
(known catalysts in related Pd-catalyzed aminooxygenations) did
not promote the vicinal oxygenation (entries 2 and 3). Although
the use of diimine ligand 2,2-bipyridine was ineffective (entry 4),
a combination of Pd(OAc)2 with BINAP resulted in formation of
hydroxyacetate 3, albeit in low yield (entry 5). In the presence of
BINAP, Pd(TFA)2 was found to be a more active catalyst precursor
than Pd(OAc)2, affording 3 in improved yield (46%) and 6:1 syn:
anti selectivity (entry 6). Encouraged by the observation that a more
non-coordinating counterion appeared to enhance catalyst activity,
we investigated the use of cationic complex [Pd(dppp)(H2O)2](OTf)2
(4).6 Although cationic Pd species are known to catalyze a range
of transformations,7 to our knowledge, their application in Pd(II)/
Pd(IV) reaction pathways has not been explored. Remarkably, 2
mol % of this catalyst efficiently catalyzed the dioxygenation of 1
to afford hydroxyacetate 3 in good yield (72%) and shorter reaction
time (2 h at 50 °C).8
unlabeled
279.1
281.1
283.1
23.4
68.3
8.3
18O-labeled
doubly 18O-labeled
a ESI/MS, [M + Na]+. b Integration of peak area.
oxygen-18 enriched water. Treatment of trans-stilbene (1) with 20
equiv of H218O in anhydrous acetic acid afforded an isotopic mixture
of hydroxyacetates 3a. The relative amounts of unlabeled hydroxy-
acetate (23.4%), oxygen-18 labeled products (68.3%), and doubly
labeled products (8.3%) were determined using mass spectrometry.
Hydrolysis of this isotopic mixture of hydroxyacetates 3a resulted
in significant remoVal of the oxygen-18 label. This result demon-
strated that the oxygen-18 label was selectively incorporated into
the carbonyl of the acetate. Upon treatment with K2CO3 and MeOH,
unlabeled diol 5a was observed as the major product (90.3%), along
with oxygen-18 labeled diol 5b (9.7%) (eq 3).9
We were surprised by the selective formation of hydroxyacetate
product 3, in preference to the corresponding diacetate, considering
that acetic acid was the solvent. To investigate the origin of the
hydroxyl group, we performed an isotopic labeling study using 97%
On the basis of this isotopic labeling study and the syn
diastereselectivity observed, we propose the mechanism shown in
9
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J. AM. CHEM. SOC. 2008, 130, 2962-2964
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C O M M U N I C A T I O N S
Table 4. Pd-Catalyzed Dioxygenation of Di- and Trisubstituted
Olefins
Figure 1. Proposed Pd(II)/(IV)-catalyzed hydroxyacetoxylation.
Table 3. Pd-Catalyzed Diacetoxylation of Representative Terminal
Olefins
entry
R
product
temp (
°C)
time (h)
yieldb (%)
1
2
3
4
5
6
7c
Ph
4-F-Ph
4-Cl-Ph
3-Cl-Ph
CH3(CH2)7
PhCH2
11a
11b
11c
11d
11e
11f
rt
rt
rt
rt
50
50
rt
2
3
2
6
3
90
94
93
97
81
71
70
3
30
BnOCH2
11g
a 0.5 mmol scale (0.1 M in AcOH), 2 mol % of catalyst 4, 1.1 equiv of
PhI(OAc)2, and 3.0 equiv of H2O; then Ac2O, rt. b Isolated yield. c 5 mol
% of catalyst 4 and 1.5 equiv of PhI(OAc)2 were used.
Figure 1. Cationic Pd complex 4 undergoes trans-acetoxypalladation
with olefin 6 to provide organopalladium intermediate 7. In accord
with previous mechanistic proposals,1b,2 oxidation of 7 with
hypervalent iodine circumvents â-hydride elimination and generates
Pd(IV) intermediate 8. Intramolecular cyclization forms acetoxo-
nium 9 and regenerates the catalyst via an SN2-type reductive
elimination. Hydrolysis of intermediate 9 delivers the syn hydroxy-
acetate product 10.
Next, we examined the generality of this novel vicinal oxidation.
As shown in Table 3, a number of terminal olefins can be elaborated
efficiently. Dioxygenation of styrene initially affords a regioisomeric
mixture (ca 1:1) of hydroxyacetate products, in accord with our
mechanistic hypothesis. Treatment of the resulting reaction mixture
with Ac2O allowed convenient isolation of diacetate 11a in 90%
yield (entry 1). In comparison to Sigman’s dimethoxylation,3 which
is highly effective for phenol derivatives, a complementary class
of styrene derivatives is tolerated. Electron-deficient styrene deriva-
tives are functionalized without the requirement of a phenol
directing group in excellent yield (greater than 90%, entries 2-4).
Moreover, simple aliphatic alkenes, such as 1-decene, allyl benzene,
and allyl benzyl ether are diacetoxylated in good yields (entries
5-7).
a 0.5 mmol scale (0.1 M in HOAc), 2 mol % of catalyst 4, 1.1 equiv of
PhI(OAc)2 and 3.0 equiv of H2O; then Ac2O, rt. b Isolated yield. c No Ac2O
was used.
strain. Diacetates 12b and 12c were formed in excellent yields and
diastereoselectivity (93% yield, 10:1 dr, entry 2 and 95% yield,
5:1 dr, entry 3). Diacetoxylation of cinnamyl ethers provided the
syn diacetate products exclusively (76% yield, >99:1 dr, entry 4
and 66% yield, >99:1 dr, entry 5). In analogy to Stahl’s aminoac-
etoxylation of allylic ethers, this high diastereocontrol can be
attributed to a more ordered transition state structure due to pre-
coordination of the allylic oxygen to Pd.
Representative 1,1-di- and trisubstituted olefins were oxidized
to produce tertiary alcohol products in good yield and with high
regioselectivity (entries 6-8). Because tertiary alcohols 12f, 12g,
and 12h were formed exclusively, the reaction mixtures were not
treated with Ac2O upon completion. The hydrolysis of acetoxonium
ions to provide tertiary alcohols selectively is in accord with
Kusumoto’s observations.10 Single-crystal X-ray analysis of 12g
verified that the hydroxy group and the acetate are indeed delivered
in a syn fashion, as predicted by our mechanistic hypothesis (syn:
anti >99:1, 83% yield, entry 7).
As shown in Table 4, dioxygenation of 1,2-, and 1,1-disubstituted
olefins provides rapid access to products bearing vicinal stereogenic
centers with good diastereocontrol. Indene and 1,2-dihydronaph-
thalene are highly reactive presumably due to their inherent ring
Finally, we would like to report our initial findings on an
intramolecular Pd-catalyzed dioxygenations of olefins to construct
tetrahydrofurans and lactones, architectures found in many natural
products.11,12 Treatment of 1-phenyl-but-3-en-1-ol with catalyst 4
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C O M M U N I C A T I O N S
Table 5. Intramolecular Pd-Catalyzed Oxidative Tetrahydrofuran
and Lactone Ring-Forming Examples
National Science and Engineering Research Council of Canada
(NSERC). V.M.D. is grateful for support from Merck Frosst.
Professor Erik Sorensen (Princeton University) is thanked for
helpful discussion.
Note Added after ASAP Publication. The version of this
paper published February 19, 2008, contained an error in Figure
2. The version published on February 22, 2008 has the correct
information.
Supporting Information Available: Experimental procedures,
spectroscopic data for all new compounds, detailed analysis of the
isotopic labeling experiment, and crystallographic data for 12g in cif
format. This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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a 0.25 mmol scale (0.1 M in wet HOAc), 1.1 equiv of PhI(OAc)2, 2 mol
% of catalyst 4. b Diastereomeric ratio. c Isolated yield. d 1.5 equiv of
PhI(OAc)2 was used. e 5 mol % Pd(TFA)2 and 5.5 mol % dppp were used.
in wet AcOH afforded tetrahydrofuran 13a in good yield as a
mixture of diastereoisomers (78% yield, 1.1:1 dr, Table 4, entry
1). Substrates bearing tertiary alcohol groups also underwent 5-endo
cyclization to generate the corresponding tetrahydrofurans 13b (90%
yield, 1.1:1 dr) and 13c (80% yield) (entries 2 and 3). As shown in
entry 4, 5-phenylpent-4-en-1-ol preferentially undergoes 5-exo
cyclization to form tetrahydrofuran 13d regioselectively (90% yield,
2.3:1 dr). By using Pd(TFA)2/dppp as the catalyst, an oxidative
lactonization occurred to give cyclic ester 13e (85% yield, 1.3:1,
entry 5). We are currently investigating the use of chiral ligands to
improve diastereselectivity and achieve enantiocontrol in these
cyclizations.
In summary, we have developed a novel method to dioxygenate
alkenes using cationic Pd catalysts. In comparison to related vicinal
oxidations, a broad range of olefins can be functionalized in both
inter- and intramolecular processes. The catalyst bears two important
structural features: an electron-rich diphosphine ligand and non-
coordinating counterions. Current studies are underway to elucidate
the effect of catalyst structure on the mechanism of this Pd(II)/
(IV) dioxygenation.
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in AcOH-d4 shows a 31P resonance at 16.73 ppm. In contrast, Pd(dppp)-
(OAc)2 resonates at 11.78 ppm. Notably, Pd(dppp)(OAc)2 does not catalyze
the desired transformation under the same reaction conditions. The
independently synthesized dppp dioxide shows a 31P resonance at ∼41
ppm. No significant amount of dppp dioxide was observed after the
complete consumption of 1. However, in the absence or after the
consumption of 1, the oxidation of dppp ligand was observed after heating
the catalyst and PhI(OAc)2 over an extended period of time.
(9) See supporting information for proposed mechanisms for the formation
of unlabeled and doubly labeled hydroxyacetates 3a.
(10) Oikawa, M.; Wada, A.; Okazaki, F.; Kusumoto, S. J. Org. Chem. 1996,
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Acknowledgment. Funding was provided by the University of
Toronto, the Connaught Foundation, Canadian Foundation for
Innovation, Ontario Ministry of Research and Innovation, and
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