A practical and mild method for the highly selective conversion of terminal alkenes into aldehydes through epoxidation-isomerization with ruthenium(IV)-porphyrin catalysts

Article abstract of DOI:10.1002/anie.200460545

Aldehydes in excellent yields were obtained from the ruthenium-porphyrin- catalyzed oxidation of various terminal alkenes with 2,6-dichloropyridine N-oxide under mild conditions. The aldehydes generated from these ruthenium-catalyzed alkene oxidations can be used in situ for olefination reactions with ethyl diazoacetate in the presence of PPh₃ in a one-pot diazoacetate olefination starting from alkenes (see example).

Full text of DOI:10.1002/anie.200460545

Communications
Alkene Oxidation
A Practical and Mild Method for the Highly
Selective Conversion of Terminal Alkenes into
Aldehydes through Epoxidation–Isomerization
with Ruthenium(iv)–Porphyrin Catalysts**
Jian Chen and Chi-Ming Che*
The Wacker-type oxidation of alkenes to carbonyl compounds
is one of the most important oxidation reactions in synthetic
chemistry and the pharmaceutical industry.[1] The conversion
=
of alkenes RCH CH2 into acetaldehyde (R = H) or methyl
ketones (R ¼ H) through the Wacker process [Eq. (1)] has
6
been well documented;[1] however, the highly selective
formation of aldehydes through catalytic oxidation of
=
=
RCH CH2 (R ¼
6
H) without C C bond cleavage [Eq. (2)]
remains a challenge. Previous work by Feringa,[2a] Murahashi,
and co-workers,[2b] and Wenzel[2c] showed that the oxidation of
aliphatic alkenes (such as oct-1-ene and dec-1-ene), N-allyl
amides/lactams, and allyl esters with O2 or air in the presence
of certain palladium or palladium/copper catalysts affords a
mixture of aldehyde and methyl ketone products. Recently,
Ho et al. reported the palladium/copper-catalyzed oxidation
of several aliphatic 1,5-dienes with O2 to form aldehydes in
60–99% yield.[2d]
During our efforts to develop new oxidation technology
based on ruthenium–porphyrin catalysts, we found that the
oxidation of a wide variety of terminal alkenes with 2,6-
[*] J. Chen, Prof. Dr. C.-M. Che
Shanghai–Hong Kong Joint Laboratory in Chemical Synthesis
Shanghai Institute of Organic Chemistry
The Chinese Academy of Sciences
354 Feng Lin Road, Shanghai 200032 (China)
Prof. Dr. C.-M. Che
Department of Chemistry and
Open Laboratory of Chemical Biology of the
Institute of Molecular Technology for Drug Discovery and Synthesis
The University of Hong Kong, Pokfulam Road (Hong Kong)
Fax: (+852)2857-1586
E-mail: cmche@hku.hk
[**] We are thankful for the financial support of The University of Hong
Kong (Generic DrugsResearch Program), the Area of Excellence
Scheme (AoE 10/01P) administered by the University Grants
Council (HKSAR), and the Hong Kong Research Grants Council
(HKU7099/01P). J.C. thanksthe Croucher Foundation of Hong
Kong for a postgraduate studentship.
Supporting information for thisarticle isavailable on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200460545
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dichloropyridine N-oxide (Cl2pyNO) in the presence of
dichlororuthenium(iv)–porphyrin catalysts [RuIV(por)Cl2]
(por= tdcpp 1, tmp 2)[3] produced aldehydes in up to 99%
induces subsequent isomerization of the epoxide to the b,g-
unsaturated aldehyde.[6] We abbreviate the epoxidation of
terminal alkenes followed by isomerization of the epoxide
products as E–I reactions.
=
yield with 100% substrate conversion without C C bond
cleavage. This unexpected ruthenium-catalyzed “Wacker-
To provide support for the above mechanism, we exam-
ined the effect of Cl2pyNO on the catalysis
(Table 1). With excess Cl2pyNO, the yield of
aldehyde 4 decreased significantly from 99 to
51%, and epoxide 5 was obtained in 49% yield.
This result could be rationalized by considering
coordination of the epoxide to active ruthenium–
porphyrin species for the isomerization reactions.
Excess Cl2pyNO would compete with the epoxide
for coordination to ruthenium, thus decreasing the
yield of the aldehyde. We found that the use of
1.01–1.03 equivalents of Cl2pyNO gave the best
results in terms of reaction time (30 min) and
aldehyde yield (99%). Changing the temperature
from room temperature to 108C or 408C did not
affect the reaction appreciably.
type oxidation” of terminal alkenes[4,5] reported herein
apparently proceeds by a different mechanism to those
proposed for the palladium- or palladium/copper-catalyzed
reactions.[2] We also report herein a direct one-pot diazoace-
tate olefination of aldehyde substrates generated in situ by
this ruthenium–porphyrin-catalyzed oxidation of alkenes.
When a solution of 1-phenyl-1,3-butadiene (3), Cl2pyNO
(1.03 equiv), and catalyst 1 (0.5 mol%) in CDCl3 was stirred
for 30 min at room temperature, the b,g-unsaturated aldehyde
4-phenylbut-3-enal (4, styrylacetaldehyde) was formed in
99% yield [Eq. (3)]. No ketone products were detected in the
reaction mixture. Similar results were obtained with CHCl3 or
Table 1: Oxidation of
3 catalyzed by 1 with varying amountsof
Cl2pyNO.[a]
Entry
Cl2pyNO [equiv]
Conversion of 3 [%]
Yield [%][b]
5
4
1
2
3
2.0
1.03
0.9
100
100
90
49
0
0
51
99
>99
[a] Reaction conditions: 3: 0.1 mmol, 1: 0.5 mol%, CDCl3: 0.5 mL; 258C,
open to air. [b] Determined by 1H NMR spectroscopy (based on
consumed substrate).
We also examined the effect of catalyst loading on the E–I
reaction. When a lower loading of 1 (0.3 mol%) was used,
with a molar ratio 3/Cl2pyNO/1 of 1:1.03:0.003, a mixture of 5,
4, and 3 was detected after the reaction. Figure 1 shows the
CH2Cl2 as the solvent. Other solvents, such as benzene,
toluene, acetone, ether, and methanol, were inferior to CHCl3
and CH2Cl2 for this catalytic process.
We propose that the 1,3-diene 3 is first oxidized by
Cl2pyNO to form epoxide 5 in the presence of catalyst 1
(Scheme 1). The same catalyst, or a derivative thereof,
Figure 1. Time-course plot for the Cl2pyNO oxidation of 3 catalyzed by
1. Reaction conditions: 3: 0.1 mmol, Cl2pyNO: 1.03 equiv, 1:
0.3 mol%, CDCl3: 0.5 mL; 178C, open to air. The product yieldswere
1
Scheme 1. Proposed mechanism for the formation of aldehyde 4 by
the Cl2pyNO oxidation of 3 catalyzed by 1.
determined by H NMR spectroscopy. More 1 (0.3 mol%) wasadded
when the reaction had proceeded for about 2.2 h.
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time course for this catalytic process. Evidently, after the
reaction had proceeded for 2h, 3 and 5 had not been
completely converted into 4. Analysis of the ruthenium–
porphyrin species in the reaction mixture revealed that
catalyst 1 had been converted into [RuII(tdcpp)(CO)].[7]
Upon subsequent addition of a new batch of 1, both 3 and 5
were completely converted into 4 in excellent yields within
15 min.
Table 3: Oxidation of terminal alkenes 20–26 with Cl2pyNO catalyzed by
1.[a]
The E–I reaction of 3 with Cl2pyNO was catalyzed equally
efficiently by 2, but less efficiently by [RuVI(tdcpp)O2]. The
oxidation of 3 with Cl2pyNO catalyzed by [RuVI(tdcpp)O2]
under similar conditions to those used with catalyst 1
(Cl2pyNO: 1.03 equiv, catalyst loading: 1.7 mol%) afforded
4
in 41% yield within 5 h. However, the complex
[RuII(tdcpp)(CO)] was a relatively inactive catalyst in the
E–I reaction.
A series of other 1,3-dienes were treated with Cl2pyNO
(1.01–1.03 equiv) and 1 (0.5–1.0 mol%) at room temperature
[Eq. (4), Table 2]. With dienes 6–10, the corresponding b,g-
unsaturated aldehydes 13–17 were obtained in 81–99% yield
and were stable enough to be purified by flash chromatog-
raphy on silica gel. However, the aldehyde product 18a,
formed in 90% yield from the oxidation of diene 11, was
converted into 18b upon flash chromatography on silica gel.
The nonterminal diene 12 was oxidized more slowly to afford
the b,g-unsaturated ketone 19 in 99% yield after a reaction
time of 6 h at 608C (Table 2, entry 7).
Entry
Substrate
T [8C]
t [h]
Product
Yield [%][b]
1
2
3
4
5
6
7
8
20
21
22
22
23
24
25
26
60
60
60
25
25
25
25
60
12
12
2
60
0.5
0.5
0.5
24
27
28
29
29
30
31
32
33
99
99
96
99
91
99
92
0[c]
[a] Reaction conditions: alkene: 0.1 mmol, Cl2pyNO: 1.03 equiv, 1: 1.0–
2.0 mol%, CDCl3: 0.5–2.0 mL; open to air. [b] Determined by GC or
1H NMR spectroscopy. [c] The corresponding epoxide was produced in
99% yield (determined by 1H NMR spectroscopy).
When styrene (20) was treated with Cl2pyNO (1.03 equiv)
and 1 (1.0 mol%) in CH2Cl2 at reflux for 5 h, styrene oxide
and phenylacetaldehyde (27) were obtained
as a mixture in 90 and 10% yield, respec-
tively.[8] To our surprise, when more of
catalyst 1 was added, and the reaction time
was increased, the styrene oxide was com-
pletely converted into aldehyde 27. For
example, the reaction of styrene with
Cl2pyNO (1.03 equiv) in the presence of
2.0 mol% of 1 in CHCl3 at 608C for 12h
afforded 27 in 99% yield; no benzaldehyde
was observed.[5] Other styrene derivatives
21–25 could also be converted into the
corresponding aryl acetaldehydes 28–32 in
excellent yields [Eq. (5) and Table 3]. How-
Table 2: Oxidation of 1,3-dienes 6–12 with Cl2pyNO catalyzed by 1.[a]
ever, with the nonaromatic alkene 26, only
Yield [%][b]
Entry
Substrate
T [8C]
t [h]
Product
the epoxide product was obtained.
Recently, the research groups of Woo,[9a]
1
2
3
4
6
7
8
25
25
25
25
25
25
60
0.5
1
13
14
15
16
17
18a
19
83
99
88
Aggarwal,[9b] and Zhang[9c] reported that the
0.5
0.5
0.5
0.5
6
iron and ruthenium meso-tetraaryl porphyr-
9
81
ins [FeII(ttp)] (H2ttp = meso-tetrakis(p-tol-
5[c]
6
10
11
12
91[d]
90
yl)porphyrin),
[FeIII(tpp)Cl],
and
[RuII(tpp)(CO)] catalyze the olefination of
certain classes of aldehydes with ethyl diaz-
oacetate (EDA) in the presence of triphe-
nylphosphane. We observed that both 1 and
7
99
[a] Reaction conditions: diene: 0.1 mmol, Cl2pyNO: 1.03 equiv, 1: 0.5–1.0 mol%, CDCl3: 0.5–1.0 mL;
open to air. [b] Determined by GC or 1H NMR spectroscopy. [c] Reaction conditions: diene: 0.65 mmol,
Cl2pyNO: 1.03 equivalents, 1: 1.0 mol%, CHCl3: 10 mL; open to air. [d] Yield of isolated product.
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[RuII(tdcpp)(CO)] also catalyze such olefination reactions.
We recognized that the aldehyde products of the 1-catalyzed
E–I reactions could be used in situ as the substrates for
olefination reactions and wanted to develop a practical one-
pot E–I–olefination reaction, that is, a one-pot diazoacetate
olefination starting directly from alkenes rather than from
aldehydes.
By using the “1+Cl2pyNO” protocol, 3 (0.1 mmol) was
converted into aldehyde 4 in CHCl3 within 30 min. Remark-
ably, upon removal of the solvent, followed by the addition of
Ph3P (1.2equiv), toluene (1 mL), and EDA (1.2equiv) and
heating the reaction mixture at 808C for 2h, the olefination
product 34 was obtained in 99% yield [Eq. (6)].
4-Oxo-4-aryl butanal derivatives are useful compounds in
organic synthesis. For example, the preparation and applica-
tion of 4-oxo-4-phenylbutanal (39) have been studied exten-
sively.[10] In this work, we found that 39 could be prepared in
52% yield (by 1H NMR spectroscopy; isolated yield: 41%)
through the E–I reaction of silyl enol ether 35 (Scheme 2).
ketones or aldehydes. The catalytic reactions reported herein
can be conducted in air at room temperature to afford a series
of isolable b,g-unsaturated aldehydes in good to excellent
yields. The present work provides a new, practical, and
convenient method for preparing multifunctionalized com-
pounds. The application of this method to the synthesis of
natural products is in progress.
Received: May 4, 2004
Keywords: homogeneouscatalysis· metalloporphyrins·
.
N ligands· oxidation · ruthenium
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1
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regioselective formation of aldehydes from terminal alkenes
=
without C C bond cleavage. This protocol supplements the
Wacker process for the oxidation of terminal alkenes to
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