Ruthenium-catalyzed oxidative cleavage of olefins to aldehydes

Article abstract of DOI:10.1021/jo010122p

Three oxidation protocols have been developed to cleave olefins to carbonyl compounds with ruthenium trichloride as catalyst (3.5 mol %). These methods convert olefins that are not fully substituted to aldehydes rather than carboxylic acids. While aryl olefins were cleaved to aromatic aldehydes in excellent yields by using the system of RuCl₃-Oxone-NaHCO₃ in CH₃CN-H₂O (1.5:1), aliphatic olefins were converted into alkyl aldehydes with RuCl₃-NaIO₄ in 1,2-dichloroethane-H₂O (1:1) in good to excellent yields. It is noteworthy that terminal aliphatic olefins were cleaved to the corresponding aldehydes in excellent yields by using RuCl₃-NaIO₄ in CH₃CN-H₂O (6:1).

Full text of DOI:10.1021/jo010122p

4814
J . Org. Chem. 2001, 66, 4814-4818
Ru th en iu m -Ca ta lyzed Oxid a tive Clea va ge of Olefin s to Ald eh yd es
Dan Yang* and Chi Zhang
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong
yangdan@hku.hk
Received J anuary 31, 2001
Three oxidation protocols have been developed to cleave olefins to carbonyl compounds with
ruthenium trichloride as catalyst (3.5 mol %). These methods convert olefins that are not fully
substituted to aldehydes rather than carboxylic acids. While aryl olefins were cleaved to aromatic
aldehydes in excellent yields by using the system of RuCl3-Oxone-NaHCO3 in CH3CN-H2O (1.5:
1), aliphatic olefins were converted into alkyl aldehydes with RuCl3-NaIO4 in 1,2-dichloroethane-
H2O (1:1) in good to excellent yields. It is noteworthy that terminal aliphatic olefins were cleaved
to the corresponding aldehydes in excellent yields by using RuCl3-NaIO4 in CH3CN-H2O (6:1).
Sch em e 1
In tr od u ction
The scission of CdC double bonds is a synthetically
important reaction to degrade large compounds or to
introduce oxygen functionality into molecules.1 For the
cleavage of olefins to carboxylic acids and ketones, a
number of methods have been developed.2,3 Most notably,
ruthenium trichloride-sodium periodate oxidation in the
CCl4-CH3CN-H2O (2:2:3) solvent system reported by
Sharpless et al. has been widely used.3 To obtain alde-
hydes from olefins that are not fully substituted, ozo-
nization of olefins followed by a reductive workup4 and
oxidative cleavage with osmium tetraoxide-sodium pe-
riodate (Lemieux-J ohnson reagent)5 are the two most
frequently employed procedures. For the sake of safety
and convenience, a great deal of efforts have been
directed at developing alternative methods to cleave
olefins to aldehydes,6,7 especially in a catalytic manner.8,9
Herein, we report three new protocols for oxidative
cleavage of a wide range of olefins to aldehydes rather
than carboxylic acids with ruthenium trichloride as the
catalyst.
Resu lts a n d Discu ssion
P r otocol I. Ru Cl3-Oxon e-Na HCO3 in CH3CN-
H2O. The protocol exemplified in Scheme 1 involves the
use of acetonitrile and water (volume ratio 1.5:1) as the
homogeneous solvent system, ruthenium trichloride as
the catalyst (3.5 mol %),10 Oxone as the primary oxidant,
(6) (a) Berkowitz and Rylander first demonstrated that stoichio-
metric amount of RuO4 could cleave olefins to aldehydes but poor yields
of aldehydes were obtained (e.g., 10% yield of adipaldehyde from
cyclohexene and 12% yield of 1-heptaldehyde from 1-octene). See:
Berkowitz, L. M.; Rylander, P. N. J . Am. Chem. Soc. 1958, 80, 6682-
6684. (b) Shalon and Elliott reported that one steroid olefin was
successfully cleaved to the corresponding aldehyde in good yield by
stoichiometric amount of ruthenium tetraoxide under neutral condi-
tion. See: Shalon, Y.; Elliott, W. H. Synth. Commun. 1973, 3, 287-
291.
* To whom correspondence should be addressed. Fax: +852-2859-
2159.
(1) Lee, D. G.; Chen, T. Cleavage Reactions. In Comprehensive
Organic Synthesis, 1st ed.; Trost, B. M., Fleming, I., Eds.; Pergamon
Press: Oxford, 1991; Vol. 7, pp 541-591.
(2) For ozonization followed by an oxidative workup, see: (a)
Fremery, M. I.; Fields, E. K. J . Org. Chem. 1963, 28, 2537-2541. (b)
Bailey, P. S. Ind. Eng. Chem. 1958, 50, 993. (c) Warnell, J . L.; Shriner,
R. L. J . Am. Chem. Soc. 1957, 79, 3165-3167. For Lemieux-von
Rudloff Oxidation and cation-exchange resin supported oxidation of
olefins using potassium permanganate, see: (d) Lemieux, R. U.; von
Rudloff, E. Can. J . Chem. 1955, 33, 1701-1709. (e) J oshi, P. L.; Hazra,
B. G. J . Chem. Res., Synop. 2000, 38-39. For ruthenium-based
methods for oxidative cleavage of olefins to carboxylic acids, see: (f)
RuCl3/NaOCl: Wolfe, S.; Hasan, S. K.; Campbell, J . R. J . Chem. Soc.,
Chem. Commun. 1970, 1420-1421. (g) RuO4/NaIO4 in aqueous acetone
solution: Stork, G.; Meisels, A.; Davies, J . E. J . Am. Chem. Soc. 1963,
85, 3419-3425. (h) Sondheimer, F.; Mechoulam, R.; Sprecher, M.
Tetrahedron 1964, 20, 2473-2485. (i) RuO2/NaIO4 in biphasic solvent
system of CCl4-H2O: Torii, S.; Inokuchi, T.; Kondo, K. J . Org. Chem.
1985, 50, 4980-4982. For CrO3-mediated oxidation, see: (j) Riegel,
B.; Moffett, R. B.; McIntosh, A. V. Organic Syntheses; Wiley: New York,
1955; Collect. Vol. III, pp 234-236. For a class of peroxotungsten
complex-mediated and tungstic acid-catalyzed oxidative cleavage of
olefins to carboxylic acids, see: (k) Antonelli, E.; D’Aloisio, R.; Gambaro,
M.; Fiorani, T.; Venturello, C. J . Org. Chem. 1998, 63, 7190-7206. (l)
Oguchi, T.; Ura, T.; Ishii, Y.; Ogawa, M. Chem. Lett. 1989, 857-860.
(3) Carlsen, P. H. J .; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J .
Org. Chem. 1981, 46, 3936-3938.
(7) (a) Lee et al. reported that stoichiometric amount of permanga-
nate on moist alumina effected cleavage of olefins to aldehydes in good
to excellent yield. See: Lee, D. G.; Chen, T.; Wang, Z. J . Org. Chem.
1993, 58, 2918-2919. For other permanganate-based methods for
cleavage of olefins to aldehydes, see: (b) Viski, P.; Szevere´nyi, Z.;
Sima´ndi, L. I. J . Org. Chem. 1986, 51, 3213-3214. (c) Wiberg, K. B.;
Saegebarth, K. A. J . Am. Chem. Soc. 1957, 79, 2822-2824. (d) Ogino,
T.; Mochizuki, K. Chem. Lett. 1979, 443. (e) Rathore, R.; Chandraseka-
ran, S. J . Chem. Res., Synop. 1986, 458-459. For the use of stoichio-
metric amount of CrO2Cl2 to cleave styrene to phenylacetaldehyde and
benzaldehyde, see: (f) Freeman, F.; Yamachika, N. J . J . Am. Chem.
Soc. 1970, 92, 3730-3733.
(8) For cobalt(II)-catalyzed oxidative cleavage of isoeugenol to
vanillin, see: Drago, R. S.; Corden, B. B.; Barnes, C. W. J . Am. Chem.
Soc. 1986, 108, 2453-2454.
(9) Recently, the use of ruthenium heteropolyanion SiRu(H2O)-
W11O395- as the catalyst enabled the cleavage of aryl olefins to aromatic
aldehydes (e.g., 98% yield of benzaldehyde from the cleavage of
styrene). However, under these conditions, aliphatic olefins usually
gave low yields of the corresponding aldehydes. See: (a) Neumann,
R.; Abu-Gnim, C. J . Chem. Soc., Chem. Commun. 1989, 1324-1325.
(b) Neumann, R.; Abu-Gnim, C. J . Am. Chem. Soc. 1990, 112, 6025-
6031. (c) Steckhan, E.; Kandzia, C. Synlett 1992, 139-140.
(10) Ruthenium(III) chloride hydrate RuCl3‚(H2O)n, purchased from
Acros, was utilized in the whole study. Calculations based on n ) 2,
RuCl3‚(H2O)2.
(4) Pappas, J . J .; Keaveney, W. P.; Gancher, E.; Berger, M. Tetra-
hedron Lett. 1966, 4273-4278.
(5) Pappo, R.; Allen, D. S., J r.; Lemieux, R. U.; J ohnson, W. S. J .
Org. Chem. 1956, 21, 478-479.
10.1021/jo010122p CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/20/2001

Ru-Catalyzed Oxidative Cleavage of Olefins to Aldehydes
J . Org. Chem., Vol. 66, No. 14, 2001 4815
Ta ble 1. Solven t Scr een in g Resu lts for th e Oxid a tive
Ta ble 2. Oxid a tive Clea va ge of Olefin s by Ru Cl3/Oxon e
a
Clea va ge of tr a n s-Stilben ea
Bu ffer ed w ith Na HCO3
entry
organic solvent
timeb (h)
yieldc (%)
1
2
3
4
CH3CNd
DME
THF
0.5
0.5
1
85
62
65
78
e
CH3CN/CCl4
1.8
a
Unless otherwise indicated, the reaction was carried out with
0.5 mmol of trans-stilbene, 0.5 mL of aqueous solution of
RuCl3‚(H2O)2 (3.5 mol %), 2 equiv of Oxone, 6.2 equiv of NaHCO3,
7.5 mL of organic solvent, and 4.5 mL of water. b Time for complete
conversion. c The percentage yield of benzaldehyde was calculated
on the basis of the GC analysis with 1,4-dichlorobenzene as the
d
internal standard. 1.5 equiv of Oxone and 4.7 equiv of NaHCO3
were employed. e 3.8 mL of CH3CN and 3.8 mL of CCl4 were used.
and sodium bicarbonate as the buffer to maintain the
neutral condition. The choice of acetonitrile as the organic
solvent was based on the solvent screening results
summarized in Table 1, in which trans-stilbene was
selected as the test substrate. Among the three homo-
geneous solvent systems, the acetonitrile-water system
gave the highest yield of benzaldehyde and required the
least amount of Oxone and sodium bicarbonate (entry 1
vs entries 2 and 3). Since carbon tetrachloride is usually
the essential solvent component in reactions using RuO4
as the oxidant,3,11 the heterogeneous solvent system
CCl4-CH3CN-H2O (ratio 1:1:1.3) was also tested. Ap-
parently, the addition of carbon tetrachloride retarded
the reaction (entry 1 vs entry 4).
While RuO2 (3.5 mol %) performed very well in the
oxidative cleavage of trans-stilbene (89% yield of benz-
aldehyde after 20 min at room temperature), RuCl3 was
still the preferred ruthenium source on the basis of cost
consideration. With only 1.7 mol % of RuCl3, trans-
stilbene was efficiently broken down to benzaldehyde
(84% yield) in 0.8 h at room temperature. However, this
low catalyst loading is not recommended for the cleavage
of electron-deficient olefins such as chalcone since the
conversion of chalcone was only 49% after 7 h. Thus, 3.5
mol % of RuCl3 was used throughout the study.
A variety of olefins (1-15) were subjected to this new
cleavage condition (Table 2). Symmetric stilbenes, trisub-
stituted aryl olefins, and styrene were cleanly cleaved to
the corresponding aromatic aldehydes (Table 2, entries
1-7). In the case of norbornylene (8), the reaction was
rapid to offer dialdehyde 16 in high yield (Table 2, entry
8), probably due to the release of ring strain.12 For
electron-deficient olefins such as chalcone (9), besides the
formation of benzaldehyde, benzoic acid was obtained as
the side product (Table 2, entry 9). Similar results were
obtained for the other three R,â-unsaturated ketones 10-
12 (Table 2, entries 10-12).13 The chiral center of (+)-
pulegone (10) was not affected in the course of the
reaction since the specific optical rotation of the product
(i.e., diacid 17) was identical to that reported.14 In the
entry
olefin
time (h)
product
PhCHO
yield (%)
1
2
3
4
5
1
0.5
0.3
0.5
0.4
0.4
85
2b
3
p-MePhCHO
p-MeOPhCHO
PhCHO
PhCHO
PhCOMe
PhCHO
Ph2CO
PhCHO
16
PhCHO
PhCO2H
17
18
19
82c
66c,d
82
4
5b
89
90c
83
6
6b
1.1
88c
73
7
8
9
7b
8
1.3
0.7
2.5
72c
70
9b
68c
91c,f
94c
88c
78c
84c
90c
10
11
12
13
14
15
10e
11e
12e
13b
14g
15g
1.6
3.4
2.2
1.1
0.6
0.3
PhCOMe
20
21
a
Unless otherwise indicated, the reaction was carried out with
0.5 mmol of olefin, 0.5 mL of aqueous solution of RuCl3‚(H2O)2
(3.5 mol %), 1.5 equiv of Oxone, and 4.7 equiv of NaHCO3 in the
solvent system of 7.5 mL of distilled CH3CN and 4.5 mL of distilled
water at room temperature; 100% conversion; the percentage yield
b
of product was obtained by GC analysis. 2 equiv of Oxone and
6.2 equiv of NaHCO3 were used. c Isolated yield. Conversion of
d
olefin 3 was 72%. e 2 mmol of olefin, 2.5 equiv of Oxone, and 7.8
equiv of NaHCO3 were used. f [R]20D ) 7.1 (c 5, MeOH). g 0.2 mmol
of olefins, 2.5 equiv of Oxone, and 7.8 equiv of NaHCO3 were used.
(11) Djerassi, C.; Engle, R. R. J . Am. Chem. Soc. 1953, 75, 3838-
3840.
(12) Shing, T. K. M.; Tam, E. K. W.; Tai, V. W.-F.; Chung, I. H. F.;
J iang, Q. Chem. Eur. J . 1996, 2, 50-57.
(13) One paper described the oxidative cleavage of olefins 10 and
11 using the Sharpless system (ref 3), which gave the same results as
ours. See: Webster, F. X.; Rivas-Enterrios, J .; Silverstein, R. M. J .
Org. Chem. 1987, 52, 689-691.
case of 1,1-disubstitued olefins 13-15, ketone products
were obtained (Table 2, entries 13-15).15 In particular,
cyclic ketones 20 and 21, known to be highly efficient
catalysts for the in situ epoxidation of olefins by Oxone,15b
were prepared in excellent yields after a flash cleavage

4816 J . Org. Chem., Vol. 66, No. 14, 2001
Yang and Zhang
Sch em e 2
Sch em e 4
Since it is known that Oxone can oxidize aliphatic
aldehydes to the corresponding carboxylic acids under
neutral conditions,19 sodium periodate was tested as the
terminal oxidant in place of Oxone to cleave aliphatic
olefins to aldehydes. We were delighted to find that
RuCl3-NaIO4 in two different solvent systems (1,2-
dichloroethane-H2O or CH3CN-H2O) could effectively
cleave a variety of olefins to aliphatic aldehydes (vide
infra), in sharp contrast to those ruthenium-catalyzed
cleavage methods reported to yield carboxylic acids as
main products.2f-i,3
Sch em e 3
P r otocol II. Ru Cl3-Na IO4 in 1,2-Dich lor oeth a n e-
H2O. The new protocol for the cleavage of cyclooctene
involved the use of sodium periodate as the terminal
oxidant and two immiscible liquid phases, i.e., 1,2-
dichloroethane and water, as the solvent system (Scheme
4). When the 1,2-dichloroethane layer was replaced by
dichloromethane or ether, the yield of 8-oxooctanal,
isolated as its bis[(2,4-dinitrophenyl)hydrazone], dropped
from 70% to 58% or 40%, respectively.
reaction. In comparison, only moderate yields (about 40%)
of those two cyclic ketones were obtained after overnight
cleavage using the method developed by Sharpless et al.3
The results shown in Table 3 indicated that this
protocol worked well for various types of olefins. Disub-
stituted aliphatic olefins such as cyclohexene underwent
facile cleavage to the corresponding dialdehydes in high
yield (Table 3, entry 1). Trisubstituted olefin 23 was
efficiently transformed to the desired keto aldehyde 24
in moderate yield (Table 3, entry 2), in contrast to the
oxidation result shown in Scheme 2. (R)-R-Terpinyl
acetate (28) was also smoothly converted to keto aldehyde
3320 in 52% yield (Table 3, entry 3), while Lemieux-
J ohnson reagent (OsO4-NaIO4) failed to cleave 1-meth-
ylcyclohexene.5 In addition, trisubstituted acyclic olefin
29 was successfully cleaved to the desired esteraldehyde
3421 in excellent yield (Table 3, entry 4). Furthermore,
electron-rich olefins such as glycal 30 and silyl enol ether
31 were subjected to the same cleavage conditions. While
formylesteraldehyde 3522 was obtained from the oxidative
cleavage of 3,4,6-tri-O-acetyl-D-glucal (30) in moderate
yield (Table 3, entry 5), silyl enol ether 31 was converted
into esteraldehyde 36 in high yield (Table 3, entry 6).
Since silyl enol ethers of ketones can be easily prepared
and purified,23 this new cleavage reaction provides a mild
and efficient way for the cleavage of ketones.24 The
oxidative cleavage of (+)-limonene (32) yielded the main
product 37,25 together with the side product 38 (Table 3,
From the cleavage results of undecylenic methyl ester
(22) and 1-phenylcyclohexene (23) (Scheme 2), it was
apparent that the RuCl3-Oxone-NaHCO3 system was
not suitable for the oxidative cleavage of olefins to
aliphatic aldehydes. Olefin 22, a monosubstituted ali-
phatic olefin, failed to give clean aldehyde product. In
the case of 1-phenylcyclohexene (23), a complex mixture
of oxidation products were obtained. The yield of ketoacid
25 was even higher than that of keto aldehyde 24.
1-Phenylcyclohexene oxide (27) was a result of the direct
epoxidation mediated by Oxone.16 However, cis-diol 2617
did not come from the hydrolysis of epoxide 27, serving
as evidence for the proposed mechanism of the cleavage
reaction (Scheme 3). A cyclic ruthenium (VI) diester18 was
probably the intermediate, which yielded keto aldehyde
24 directly and cis-diol 26 by hydrolysis.
(14) The specific optical rotation of (+)-3-methyladipic acid (17) was
[R]20 ) 7.1 (c 5, MeOH). The reported value (Aldrich catalog no.:
D
M2,738-7) was [R]21 ) 7.2 (c 5, MeOH). The 1994-1995 Catalog
Handbook of Fine Chemicals; Aldrich Chemical Co., Inc.: Milwaukee,
1994; p 924.
(15) Under the experimental conditions of protocol I, dioxiranes
could, in principle, be generated in situ from ketones and Oxone.
However, no epoxidation product was detected from the cleavage
reactions of 5, 6, and 13-15. This suggested that epoxidation reactions
catalyzed by ketones could not compete with the fast cleavage reactions.
For examples of epoxidation reactions mediated by dioxiranes gener-
ated in situ from ketones, see: (a) Yang, D.; Wong, M.-K.; Yip, Y.-C.
J . Org. Chem. 1995, 60, 3887-3889. (b) Yang, D.; Yip, Y.-C.; Tang,
M.-W.; Wong, M.-K.; Cheung, K.-K. J . Org. Chem. 1998, 63, 9888-
9894. (c) Yang, D.; Yip, Y.-C.; J iao, G.-S.; Wong, M.-K. J . Org. Chem.
1998, 63, 8952-8956. (d) Denmark, S. E.; Forbes, D. C.; Hays, D. S.;
DePue, J . S.; Wilde, R. G. J . Org. Chem. 1995, 60, 1391-1407.
(16) A control experiment showed that Oxone buffered with NaHCO3
could even epoxidize 1-phenylcyclohexene (23) to the corresponding
epoxide 27 in 41% yield after 4.8 h.
(19) Zheng, T.-C.; Richardson, D. E. Tetrahedron Lett. 1995, 36,
833-836.
(20) A literature preparation of compound 33 involved a two-step
scheme, i.e., dihydroxylation of compound 28 with potassium perman-
ganate followed by the oxidative cleavage of the resulting diol with
lead tetraacetate. See: Traber, B.; Pfander, H. Tetrahedron 1998, 54,
9011-9022.
(21) CAS registry number for esteraldehyde 34 is 76712-40-8.
Strobel, M. P.; Morin, L.; Paquer, D. Fr. Nouv. J . Chim. 1980, 4, 603-
608.
(22) Perlin, A. S. Can. J . Chem. 1963, 41, 555-561.
(23) Mander, L. N.; Sethi, S. P. Tetrahedron Lett. 1984, 25, 5953-
5956.
(24) For other methods of oxidative cleavage of silyl enol ethers,
see: (a) Ozonization: Clark, R. D.; Heathcock, C. H. J . Org. Chem.
1976, 41, 1396-1403. (b) MoO2(acac)2-t-BuOOH: Kaneda, K.; Kii, N.;
J itsukawa, K.; Teranishi, S. Tetrahedron Lett. 1981, 22, 2595-2598.
(17) The 1H NMR and 13C NMR data of compound 26 were identical
to those reported. Kobayashi, S.; Endo, M.; Nagayama, S. J . Am. Chem.
Soc. 1999, 121, 11229-11230.
(18) For the first report on the isolation of a cyclic ruthenium(VI)
diester, see: Piccialli, V.; Sica, D.; Smaldone, D. Tetrahedron Lett. 1994,
35, 7093-7096.

Ru-Catalyzed Oxidative Cleavage of Olefins to Aldehydes
J . Org. Chem., Vol. 66, No. 14, 2001 4817
Ta ble 3. Oxid a tive Clea va ge of Alip h a tic Olefin s by
Ru Cl3/Na IO4 in ClCH2CH2Cl/H2Oa
Ta ble 4. Resu lts for Oxid a tive Clea va ge of
Mon osu bstitu ted Alip h a tic Olefin sa
convn
yield of
yield of
entry olefin solvent system
(%) aldehydeb (%) diolb (%)
1
22
42
45
22
22
22
22
22
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
1,4-dioxane/H2O
THF/H2O
100
100
100
79
75
81
94
95
86
71
64
59
25
56
3
0
0
1.3
8
17
9
23
2c
3d
4e
5e
6e
7e
8e, f
DME/H2O
CH3CN/H2O
88
96
entry
olefin
time (h)
product (yield, %)b
a
1c
2e
3e,f
4
cyclohexene
0.7
2.8
1.5
1.7
3.5
2
adipaldehyde (70)d
24 (55)
33 (52)
34 (80)
35 (50)
36 (75)
37 (38) + 38 (10)
PhCHO (70)
Unless otherwise indicated, the reaction was carried out with
1 mmol of monosubstituted aliphatic olefin, 1 mL of aqueous
solution of RuCl3‚(H2O)2 (3.5 mol %), 2 mmol of NaIO4, and 6 mL
23
28
29
30
31
32
1
b
of organic solvent at room temperature for 1.5 h. Isolated yield.
d
c The reaction time was 1.6 h. The reaction time was 1.1 h. e 1.5
5
6
equiv of NaIO4 was used. f The volume ratio of CH3CN to H2O
was 3/1, and the reaction time was 0.5 h.
7e, g
8h
10
1.2
conversion of 22 was only 38% after 2 h and the
percentage yield of the desired cleavage product 40,27 an
esteraldehyde, was 50% based on the recovered 22. Thus,
the following system of RuCl3-NaIO4 in a homogeneous
solvent mixture CH3CN-H2O was developed to cleave
monosubstituted aliphatic olefins.
a
Unless otherwise indicated, the reaction was carried out with
1 mmol of olefin, 1 mL of aqueous solution of RuCl3 (3.5 mol %),
2 equiv of NaIO4, 5 mL of distilled 1,2-dichloroethane, and 4 mL
of distilled water at room temperature. Isolated yield. c 5 mmol
of olefin, 5 mL of an aqueous solution of RuCl3 (3.5 mol %), 1.5
equiv of NaIO4, 20 mL of distilled 1,2-dichloroethane, and 15 mL
b
d
of distilled water at room temperature were used. Isolated as
P r otocol III. Ru Cl3-Na IO4 in CH3CN-H2O. For
monosubstituted aliphatic olefins, such as 22, dodecene-1
(42), and 45, the optimized reaction system includes the
use of the homogeneous solvent system of CH3CN-H2O
(volume ratio 6:1) and 2 equiv of NaIO4 (Table 4, entries
1-3). Other homogeneous solvent systems, such as 1,4-
dioxane-H2O, THF-H2O, or DME-H2O, were found to
be less efficient (Table 4, entries 4-7). Increasing of the
amount of NaIO4 from 1.5 to 2 equiv resulted in a
complete reaction and an excellent yield of aldehyde 40
(Table 4, entries 1 vs 4). The ratio of CH3CN to H2O was
found to be crucial for the cleavage of 22. When the ratio
of CH3CN to H2O was 3:1, yields of aldehyde 40 and diol
4128 were 56% and 23%, respectively (Table 4, entry 8).
However, with the increase of the CH3CN/H2O ratio to
6:1, the isolated yield of aldehyde 40 was improved to
71% and the formation of diol 41 was suppressed to only
1.3% (Table 4, entry 4). This can be explained according
to the mechanism shown in Scheme 3. The reduction of
water content in the cleavage system disfavored the
hydrolysis of cyclic ruthenium(VI) diester to diol.
bis[(2,4-dinitrophenyl)hydrazone]. e 5.2 mol % of RuCl3 was em-
ployed to achieve a rapid reaction. f 70% conversion. 4 equiv of
g
h
NaIO4 was employed. 81% conversion.
Sch em e 5
entry 7). Finally, trans-stilbene was cleaved to benz-
aldehyde in 70% yield, but apparently this reaction
was quite slow compared with that under the RuCl3-
Oxone-NaHCO3 system (entry 8 of Table 3 vs entry 1 of
Table 2).
As shown in Scheme 5, olefin 29 was oxidized to
carboxylic acid 3926 in quantitative yield when the
amount of NaIO4 was increased from 2 to 3 equiv and
the reaction time was prolonged to 24 h. This indicates
that the desired oxidation product, either an aldehyde
or a carboxylic acid, could be obtained with RuCl3-NaIO4
in an 1,2-dichloroethane-H2O system by simple manipu-
lation of the amount of terminal oxidant and the reaction
time.
The cleavage system developed by Sharpless et al. (i.e.,
RuCl3-NaIO4 in CCl4-CH3CN-H2O) can oxidize ethers
to esters.3 However, excellent chemoselectivity was ob-
served in the cleavage of olefin 4529 using our oxidation
system of RuCl3-NaIO4 in CH3CN-H2O (6/1) (Table 4,
entry 3). The benzyl ether group, a commonly used
When monosubstituted aliphatic olefin 22 was sub-
jected to the reaction conditions shown in Scheme 4, the
(25) The 1H NMR data of keto aldehyde 37 was identical to that
reported. See: Griesbaum, K.; Hilaˆ, M.; Bosch, J . Tetrahedron 1996,
52, 14813-14826.
(27) Kubo, I.; Kim, M.; Ganjian, I.; Kamikawa, T.; Yamagiwa, Y.
Tetrahedron 1987, 43, 2653-2660.
(28) Hassarajani, S. A.; Subaraman, A. S.; Mamdapur, V. R. Org.
Prep. Proced. Int. 1994, 26, 571-573.
(26) The 1H NMR and 13C NMR data of 39 were identical to those
reported. See: Foubelo, F.; Lloret, F.; Yus, M. Tetrahedron 1992, 48,
9531-9536.

4818 J . Org. Chem., Vol. 66, No. 14, 2001
Yang and Zhang
equiv) in CH3CN (7.5 mL) and distilled water (4.5 mL) was
added in portions a mixture of Oxone (460 mg, 0.75 mmol) and
NaHCO3 (196 mg, 2.3 mmol) over a period of 10 min at room
temperature. The color turned from black to yellow im-
mediately. The reaction was monitored by TLC. After comple-
tion in 28 min, the reaction was quenched with saturated
aqueous solution of NaS2O3 and then extracted with CH2Cl2
twice. The combined organic layer was washed with water and
brine, respectively, dried over anhydrous MgSO4, and filtered.
The organic layer was subjected to GC analysis to determine
the percentage yield of benzaldehyde using 1,4-dichloroben-
zene as an internal standard.
hydroxyl protecting group, was kept intact over the
course of the cleavage reaction.
Con clu sion
We have developed three ruthenium-based catalytic
oxidation methods for cleavage of a wide range of olefins
to aldehydes. As ruthenium trichloride is easy to handle
and is much less expensive and toxic than OsO4, these
cleavage methods are expected to be useful in organic
synthesis.
P r otocol II. Ru Cl3-Na IO4 in 1,2-Dich lor oeth a n e-H2O.
To a stirred mixture of compound 31 (212 mg, 1 mmol) and
RuCl3 stock solution (1 mL, 0.035 mmol, 3.5 mol %) in 1,2-
dichloroethane (5 mL) and distilled water (4 mL) was added
in portions NaIO4 (428 mg, 2 mmol) over a period of 5 min at
room temperature. The color turned from black to yellow
immediately. The reaction was monitored by TLC. After
completion in 2 h, the reaction was quenched with saturated
aqueous solution of Na2S2O3, and the two layers were sepa-
rated. The aqueous layer was extracted with EtOAc three
times. The combined organic layer was washed with water and
brine, respectively, dried over anhydrous MgSO4, filtered, and
concentrated. The residue was purified by flash column
chromatography to give desired aldehyde 36 (183 mg, 75%)
as a colorless oil. Analytical TLC (silica gel 60), 10% EtOAc in
n-hexane, Rf ) 0.14; 1H NMR (300 MHz, CDCl3) δ 9.75 (t, J )
1.4 Hz, 1H), 2.46 (t, J ) 6.7 Hz, 2H), 2.33 (t, J ) 6.7 Hz, 2H),
1.63 (m, 4H), 0.90 (s, 9H), 0.25 (s, 6H); 13C NMR (75.47 MHz,
CDCl3) δ 202.14, 173.68, 43.51, 35.59, 25.63, 25.51, 24.46,
21.44, -3.62, -4.85; IR (CHCl3) 1722, 1712 cm-1; EI-MS (20
eV) m/z 244 (M+, 1), 243 (M+ - 1, 4), 185 (M+ - 59, 78), 163
Exp er im en ta l Section
Gen er a l In for m a tion . Ruthenium(III) chloride hydrate,
Oxone, and sodium periodate were purchased from Acros.
Commercially available olefins were purchased from Acros or
Aldrich and directly used without further purification. CH3-
CN and 1,2-dichloroethane were distilled before use. Syntheses
of substituted stilbenes 2 and 3 were carried out according to
the literature procedure.30 Preparation of cyclohexene deriva-
tive 31 was performed following the reported method.23 Flash
column chromatography was performed on E. Merck silica gel
60 (230-400 mesh ASTM) using ethyl acetate/n-hexane as
eluting solvents. The known cleavage products were identified
by comparison of the spectral and physical data with those
reported. GC analysis was performed on a HP-6890 capillary
gas chromatography using a flame ionization detector (FID),
a 25 m × 0.32 mm × 0.52 µm HP-Ultra 1 (cross-linked methyl
silicone gum) capillary column, or a 30 m × 0.32 mm × 0.5
µm HP-INNOWAX (cross-linked poly(ethylene glycol)) capil-
lary column, with helium as the carrier gas. A stock solution
of ruthenium(III) chloride was prepared by dissolving RuCl3‚
(H2O)2 (842 mg, 3.5 mmol) in 100 mL of distilled water (the
concentration was 0.035 M). This aqueous solution was stable
for several months at room temperature.
(99), 75 (100); HRMS-EI m/z for
C
12H24SiO3 (M+) calcd
244.1495, found 244.1486.
P r otocol III. Ru Cl3-Na IO4 in CH3CN-H2O. The proce-
dure was identical to that of protocol II shown above, except
that CH3CN was used as the organic solvent in the cleavage
reactions and the ratio of CH3CN to H2O was 6:1.
Typ ica l P r oced u r es for t h e Oxid a t ive Clea va ge of
Olefin s. P r otocol I. Ru Cl3-Oxon e-Na HCO3 in CH3CN-
H2O. To a stirred mixture of trans-stilbene (90 mg, 0.5 mmol)
and RuCl3 stock solution (0.5 mL, 0.0175 mmol, 3.5 mol %
Ack n ow led gm en t. This work was supported by The
University of Hong Kong.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for compounds 33-40, 43, and 46. This material
is available free of charge via the Internet at http://pubs.acs.org.
(29) The 1H NMR data of aldehyde 46 was identical to that reported.
See: Naito, H.; Kawahara, E.; Maruta, K.; Maeda, M.; Sasaki, S. J .
Org. Chem. 1995, 60, 4419-4427.
(30) Ogawa, K.; Sano, T.; Yoshimura, S.; Takeuchi, Y.; Toriumi, K.
J . Am. Chem. Soc. 1992, 114, 1041-1051.
J O010122P