An improved protocol for the oxidative cleavage of alkynes, alkenes, and diols with recyclable Ru/C

Article abstract of DOI:10.1055/s-0028-1087933

Efficient synthesis of carboxylic acids from alkynes; aldehydes from alkenes and diols employing Ru/C-based recyclable catalytic system is reported with good to excellent yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087933

LETTER
739
An Improved Protocol for the Oxidative Cleavage of Alkynes, Alkenes, and
Diols with Recyclable Ru/C
O
xidative Cleava
g
i
e
of
A
l
j
kynes,
a
Alkenes, an
y
d
D
iols Kumar A., V. Prakash Reddy, R. Sridhar, B. Srinivas, K. Rama Rao*
Organic Chemistry Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
E-mail: kakulapatirama@gmail.com
Received 21 October 2008
(Scheme 1). Alkyne consumption was achieved within
2.5 hours (as monitored by TLC). Further workup and ex-
traction gave analytically pure benzoic acid in 88% yield,
without the need of further purification by column chro-
Abstract: Efficient synthesis of carboxylic acids from alkynes; al-
dehydes from alkenes and diols employing Ru/C-based recyclable
catalytic system is reported with good to excellent yields.
Key words: oxidation, Ru/C, supported catalyst, alkenes, alkynes,
diols, carboxylic acids
1
matography, confirmed by H NMR and melting point.
With this result, the amount of catalyst was optimized.
The best-optimized conditions were found to be 1 mol%
ruthenium within 6.5 hours affording carboxylic acid in
90% yield at ambient conditions.16 The scope of the sub-
strates was further explored using various alkynes (see
Table 1), and good to excellent yields show the versatility
of the catalyst in oxidizing the alkynes.
Ruthenium-catalyzed organic oxidations are well known
for applications in organic synthesis.1 The oxidation of al-
cohols with the famous Ley–Griffith reagent (TPAP),2a–d
cis-dihydroxylation of alkenes,3a–c oxidative cleavage of
olefins to aldehydes and ketones,4a alkynes and diols to
carboxylic acids with NaIO4 and Oxone protocols,4b,c ox-
idative preparation of hypervalent iodine compounds,5
oxidative cyclizations,6 and ketohydroxylation of
olefins7a,b are all well-established methodologies. Char-
coal-supported catalysts like Pd/C,8a–c Ni/C,9a,b and Cu/
C10a–c have been developed over the past decade and have
found wide applications in synthesis. Methods based on
supported versions of ruthenium11a,b are booming over the
years. Ruthenium-supported catalysts, such as ruthenium
nanoparticles grafted onto hydroxyapatite (nano-Ru-
HAP),12 Ru/Al2O3,13 and Ru/AlO(OH),14 have become
prominent recently for the oxidation of alkenes, alkynes,
and alcohols to organic acids owing to their recyclability.
However, only very few reports are found in literature
with charcoal-supported ruthenium (Ru/C).15 But in many
cases, along with aldehydes and carboxylic acids, many
unwanted side products are also formed. Apart from this,
the use of ruthenium complexes and perchlorate salts
makes it costly and unsafe. A more viable and simple cat-
alytic system that can be performed at room temperature
may offer an easy-to-handle method for doing these oxi-
dative transformations. Herein, we report for the first time
a recyclable catalytic system for performing the oxidative
cleavage of alkynes to carboxylic acids and alkenes to al-
dehydes, respectively, by using Ru/C (5% grafted), which
can be reused without loss of activity. In this methodolo-
gy, Ru/C (5%) was used. Initially, oxidation of phenyl-
acetylene (1 mmol, 120 mL) was checked using Ru/C (2.5
mol%, 50 mg) in a biphasic solvent of water–acetonitrile
(1:1, 5 mL), NaHCO3 (2.5 equiv) at room temperature us-
ing Oxone (614 mg, 1 mmol) as the stoichiometric oxidant
Table 1 Oxidation of Alkynes with Ru/Ca
Entry Alkyne
1
Time Product
(h)
Yield
(%)b
COOH
6.5
90
2
6.5
81
COOH
MeO
3
8.0
76
78
COOH
HO
HO
4
6.5
COOH
5
S
6
8.0
S
86
94
COOH
COOH
7.0
7
7.5
89
91
COOH
MeO
MeO
8
7.0
COOH
a With oxone as oxidant.
b Isolated yield.
SYNLETT 2009, No. 5, pp 0739–0742
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Advanced online publication: 25.02.2009
DOI: 10.1055/s-0028-1087933; Art ID: G35008ST
© Georg Thieme Verlag Stuttgart · New York

740
V. Kumar A. et al.
LETTER
A scale-up reaction was also performed to check its via-
bility. To phenylacetylene (100 mmol, 12 mL) taken in a
250 mL round-bottom flask was added Ru/C (1 mol%, 2
g) in a biphasic solvent of water–acetonitrile (1:1, 50 mL)
followed by NaHCO3 (2.5 equiv), Oxone (61.4 g, 100
mmol) at room temperature. Workup and extraction after
6.5 hours gave benzoic acid in (89% yield, 10.8 g). Fur-
ther we were interested in the catalyst recyclability. We
have performed a control experiment with phenylacety-
lene to benzoic acid at ambient conditions, in which Ru/C
was recovered. This experiment gave consistent conver-
sions up to five cycles. The catalyst was washed with wa-
ter (2 × 10 mL), centrifuged, oven-dried, and charged
with the same solvent system. The results are summarized
in Table 2. Further to check the leaching of ruthenium, the
following experiment was carried out: Ru/C (5 mol%)
was taken in the solvent system (acetonitrile and water,
1:1, 25 mL), and Oxone (3.07 g, 5 equiv) was added and
stirred for overnight. The charcoal was separated by filtra-
tion, and to the filtrate was added phenylacetylene (600
mL, 5 mmol) and checked for any conversion to benzoic
acid. But no conversion of alkyne was observed even after
stirring for 24 hours. Henceforth, we have concluded that
there was no leaching of ruthenium from charcoal.
back to cycle
Ru/C
ruthenium
oxidation
RCOOH
or
+
O
O
RCHO
electrocyclic
fragmentation
O
O
= ruthenium
or
R
R
= charcoal
Scheme 2 Proposed mechanistic pathway for the Ru/C-catalyzed
oxidation
sults. The oxidants H2O2 and NaOCl were sluggishly oxi-
dizing styrene whereas Oxone was not working even
under heating at 80 °C. Then, various solvents were
screened for the solvent stabilization of the reaction sys-
tem with NaIO4. When 1,2-dichoroethane–water (1:1)
was used as the solvent, oxidation of styrene could not be
controlled at the aldehyde stage (aldehyde and carboxylic
acid were formed in the ratio of 6:4). The use of the sol-
vents ethanol, methanol, propanol, isopropanol, and tert-
butanol also led to the formation of carboxylic acid as the
side product. The best solvent and temperature was found
to be a combination of ethyl acetate, acetonitrile, and
water (1:1:1, 4.5 mL) at 0 °C, and this solvent system was
utilized with Ru/C (2.5 mol%, i.e., 50 mg) and 1.1 equiv-
alents of NaIO4 as the oxidant over styrene at 0 °C to af-
ford 81% of benzaldehyde within 3.5 hours with no side
products. No change in the results was observed when 1
mol% and 2 mol% of ruthenium were used, and hence the
reactions were performed with 1 mol% of ruthenium.
With the solvent stabilization and catalyst stabilization in
hand, the scope of the substrates was further explored
(Table 3).
Table 2 Control Experiment for the Recovery of Ru/C
Ru/C
Yield (%)
Cycle 1
Cycle 2
Cycle 3
Cycle 4
Cycle 5
89
89
88
88
87
Ru/C (1mol%)
COOH
R
R
Oxone, r.t.
MeCN–H2O (1:1)
6.5–8 h
Best results were obtained with the aryl-substituted sub-
strates as compared to the alkyl ones. A good conversion
of various diols was also observed. The chiral enone (+)-
pulegone (entry 22, Table 3) gave (+)-3-methyl adipic
acid without any racemization during the reaction as ob-
served from the optical rotation comparable with the ear-
Ru/C (1mol%)
CHO
R
NaIO4, 0 °C
MeCN–EtOAc–H2O (1:1:1)
1.5–3 h
R
1
lier report.17 All the products were characterized by H
= charcoal
NMR and IR spectroscopy, mass spectrometry, and by
comparison with the known compounds.3,4
= ruthenium
After the reactions, Ru/C was separated by centrifugation,
washed with water, and oven-dried overnight. This dried
charcoal was reused for three more cycles, and the results
were consistent. Based on the studies done over rutheni-
um-catalyzed reactions we proposed a plausible mecha-
nistic-pathway rationale to the observed experimental
results (Scheme 2).
Scheme 1 Ru/C-catalyzed oxidation of alkynes, alkenes
However, when we wanted to extend this oxidation to al-
kenes, the oxidation of styrene was examined with various
oxidants like H2O2, NaOCl, Oxone, and NaIO4 at room
temperature. The reaction with NaIO4 only gave good re-
Synlett 2009, No. 5, 739–742 © Thieme Stuttgart · New York

LETTER
Oxidative Cleavage of Alkynes, Alkenes, and Diols
741
Table 3 Oxidation of Various Olefins with Ru/Ca (continued)
Entry Alkene
TimeProduct
(h)
Yield
(%)b
CHO
F
9
3.5
89
F
CHO
10
3.5
85
81
Figure 1 Scanning electron microscope (SEM) images: (a) SEM
image of the native unused Ru/C; (b) SEM image of the used Ru/C
after 5 cycles.
Cl
Cl
CHO
11
3.5
As can be seen from the SEM images (Figure 1), rutheni-
um may exist in a clustered form and undergoes oxidation
at the surface. Then alkyne–alkene addition followed by
the electrocyclic rearrangement yields the product and Ru
further goes back to the cycle.
Cl
Cl
CHO
12
13
3
92
87
In conclusion we have developed a facile methodology
with recyclable ruthenium for oxidizing various alkynes,
alkenes, and diols in good to excellent yields. This meth-
odology overcomes the various drawbacks associated
with the existing methodologies like nonrecyclability of 14
expensive ruthenium and formation of side products re-
CHO
CHO
3
8
61
42
36
5
5
sulting in the low yields of the oxidized products.
15
7.5
CHO
OHC
Table 3 Oxidation of Various Olefins with Ru/Ca
16
8
OHC
CHO
Entry Alkene
TimeProduct
(h)
Yield
(%)b
17
8
65
82c
59
CHO
CHO
CHO
Ph
OHC
1
4.0
3.5
74c
Ph
CHO
HO
Ph
OH
18d
19e
1.5
2
81
Ph
OH
2
CHO
CHO
OHC
3
3.5
76
71
OH
Cl
Cl
OH
20e
21e
2
43
74
CHO
OHC
CHO
4
5
3.5
3.5
OH
OH
OH
CHO
2.5
CHO
OHC
69
63
O
22f
8
67g
HOOC
CHO
COOH
6
3.5
a Using NaIO4 as oxidant.
b Isolated yield.
CHO
CHO
c With respect to 2 equiv of benzaldehyde formed.
d meso-Hydrobenzoin.
7
4.5
67
65
e trans-diols racemic mixture.
f (+)-Pulegone.
NO2
NO2
g Specific optical rotation same as ref. 4c.
8
4.5
The 1H NMR spectra were recorded on Varian Gemini 200 MHz or
Bruker Avance 300 MHz spectrometers in CDCl3 with TMS as in-
ternal standard. Mass spectra were recorded on a Finnigan MAT
1020 mass spectrometer operating at 70 eV. The SEM images were
Cl
Cl
Synlett 2009, No. 5, 739–742 © Thieme Stuttgart · New York

742
V. Kumar A. et al.
LETTER
recorded on Hitachi S3000N instrument. Ruthenium (5% on car-
bon) was purchased from Lancaster synthesis (CAS no 74401-8-8).
T.; Kozaki, A.; Monguchi, Y.; Sajiki, H. Chem. Eur. J. 2007,
13, 5937.
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Acknowledgment
V. K. A. thanks UGC, New Delhi. V.P.R., R.S. and B.S. thank
CSIR, New Delhi for research fellowships.
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Alkynes
Ruthenium (1 mol%, Ru/C, 20 mg), alkyne (1 mmol), Oxone
(1 equiv), and NaHCO3 (2.5 equiv) were taken in a round-
bottom flask (25 mL) with a magnetic stir bar. Then, a
mixture of H2O–MeCN (1:1, 5 mL) was added and stirred
until complete consumption of the alkyne was observed as
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and NaIO4 (214 mg, 1.1 equiv), were taken in a mixture
EtOAc–MeCN–H2O (1:1:1, 4.5 mL) in a 25 mL round-
bottom flask with a magnetic stir bar and stirred until
complete consumption of the alkene/diol was observed as
monitored by TLC. The reaction mixture was extracted with
EtOAc (3 × 10 mL), the combined organic layers were dried
over anhyd Na2SO4, and concentrated to give the
analytically pure product.
(17) Specific optical rotation of the product (+)-3-methyladipic
acid was [a]D20 7.1 (c 5, MeOH).
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