Selective ruthenium-catalyzed oxidation of 1,2:4,5-di-O-isopropylidene-β-D-fructopyranose and other alcohols with NaOCl

Article abstract of DOI:10.1021/ol025705f

Matrix presented The asymmetric epoxidation catalyst 1,2:4,5-di-O-isopropylidene-β-D-erythro-2,3-hexadiulo-2,6-pyranose 2 was obtained in high yield from 1,2:4,5-di-O-isopropylidene-β-D-fructopyranose 1 via a recyclable ruthenium-catalyzed hypochlorite oxidation protocol under biphasic conditions (MTBE/water) in the presence of an alkaline buffer (pH 9.5). Other secondary alcohols were also oxidized selectively to the correspondinq ketones.

Full text of DOI:10.1021/ol025705f

ORGANIC
LETTERS
2002
Vol. 4, No. 10
1659-1661
Selective Ruthenium-Catalyzed
Oxidation of 1,2:4,5-Di-O-isopropylidene-
â-D-fructopyranose and Other Alcohols
with NaOCl
Luca Gonsalvi,† Isabel W. C. E. Arends, and Roger A. Sheldon*
Laboratory for Biocatalysis and Organic Chemistry, Delft UniVersity of Technology,
Julianalaan 136, 2628 BL Delft, The Netherlands
r.a.sheldon@tnw.tudelft.nl
Received February 12, 2002
ABSTRACT
The asymmetric epoxidation catalyst 1,2:4,5-di-O-isopropylidene-â-D-erythro-2,3-hexadiulo-2,6-pyranose 2 was obtained in high yield from
1,2:4,5-di-O-isopropylidene-â-D-fructopyranose 1 via a recyclable ruthenium-catalyzed hypochlorite oxidation protocol under biphasic conditions
(MTBE/water) in the presence of an alkaline buffer (pH 9.5). Other secondary alcohols were also oxidized selectively to the corresponding
ketones.
The selective oxidation of alcohols to aldehydes (primary)
and ketones (secondary) is a highly desired conversion in
industry and academia. From economical and environmental
standpoints, there is a need for catalytic systems able to
achieve this transformation working at low concentration of
transition metals and releasing the lowest amount of byprod-
ucts and waste (i.e., atom-efficient processes1). Both het-
erogeneous2 and homogeneous3 catalytic systems using clean
terminal oxidants such as O2 or H2O2 have been successfully
applied to the oxidation of activated and unactivated alcohols.
RuO4 is a selective stoichiometric oxidant for alcohols,
comparable to dichromate4 or KMnO4,5 still utilized in many
industrial applications. It can be generated in situ by addition
of an oxidant such as NaIO4 or NaBrO3 to a ruthenium
precursor and used in catalytic amounts. The major drawback
of these systems is usually the cost of the oxidant and the
large amount of waste salts produced. NaOCl, which can
also be used to generate RuO4, is a cheap oxidant, and its
byproduct is sodium chloride. Oxidation of organic substrates
via sodium hypochlorite has been reported, with6 or without7
a catalytic amount of ruthenium.
* To whom correspondence should be addressed. Fax: +31 15 2781415.
Tel: +31 15 2782675.
† Current address: Institute for the Chemistry of Organometallic
Compounds, National Research Council, ICCOM-CNR, Via J. Nardi 39-
41, 50132 Firenze, Italy.
The selective conversion of 1,2:4,5-di-O-isopropylidene-
â-D-fructopyranose 1 into 1,2:4,5-di-O-isopropylidene-â-D-
(1) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259. Trost, B.
M. Science 1991, 254, 1471. Sheldon, R. A. Top. Curr. Chem. 1993, 164,
21.
(2) Kaneda, K.; Yamashita, T.; Matsushita, T.; Ebitani, K. J. Org. Chem.
1998, 63, 1750. Matsushita, T.; Ebitani, K.; Kaneda, K. Chem. Commun.
1999, 265. Hinzen, B.; Lenz, R.; Ley, S. V. Synthesis 1998, 977.
(3) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis
1994, 639. Barak, G.; Dakka, J.; Sasson, Y. J. Org. Chem. 1988, 53, 3553.
Sheldon, R. A.; Arends, I. W. C. E.; Dijksman, A. Catal. Today 2000, 57,
157 and references therein.
(4) Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic Chemistry;
Springer: Berlin, 1984. Sheldon, R. A.; Kochi, J. K. Metal-Catalysed
Oxidations of Organic Compounds; Academic Press: New York, 1981.
(5) Menger, F. M.; Lee, C. Tetrahedron Lett. 1981, 22, 1655.
(6) Balavoine, G.; Eskenazi, C.; Meunier, F. J. Mol. Catal. 1985, 30,
125. Wolfe, S.; Hasan, S. K.; Campbell, J. R. Chem. Commun. 1970, 1420.
(7) Stevens, R. V.; Chapman, K. T.; Weller, H. N. J. Org. Chem. 1980,
45, 2030.
10.1021/ol025705f CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/17/2002

erythro-2,3-hexadiulo-2,6-pyranose 2 is a particularly inter-
esting target reaction for alcohol oxidation. Ketone 2 was
used as a precursor for transition-metal-free catalytic asym-
metric olefin epoxidation by Shi and co-workers8 and was
obtained from fructose diacetonide 1 in 93% yield by use of
an excess of pyridinium chlorochromate (Scheme 1).8,9
The method was applied to the oxidation of 1 to 2 and,
for comparison, to a series of unfunctionalized secondary
alcohols. The results, summarized in Table 1, show that all
Table 1. Oxidation of Secondary Alcohols via TPAP/NaOCla
substrate
product
% convb
% yieldb
1c
2
98
99
99
99
90
97
90
99
99
88
89
96
Scheme 1. Stoichiometric Oxidation of 1 to 2 via Pyridinium
2-octanol
borneol
cyclohexanol
1-phenyl ethanol
2-adamantanold
2-octanone
camphor
cyclohexanone
acetophenone
2-adamantanone
Chlorochromate (PCC)
a Reactions were carried out over 4 h at rt in a 50-mL two-necked pear-
shaped flask containing the substrate (5 mmol), TPAP (0.25 mol %), EtOAc
(5 mL), and NaHCO3/Na2CO3 buffer solution (pH 9.5, 5 mL). The flask
was equipped with a pH electrode and a dropping funnel from which the
oxidant (NaOCl 0.7 M, 1 equiv) was added dropwise over 2 h. b GC
conversions and yields, based on pure samples. c TPAP 1 mol %, NaOCl
3 equiv, MTBE instead of EtOAc. d TPAP 0.5 mol %, MTBE instead of
EtOAc.
Catalytic oxidation of 1 has proved particularly difficult,
probably because of steric reasons. Methods such as Co/
NHPI/O2,10 TPAP/O2,3 Ru/TEMPO/O2,11 Pd(L-L)(AcO)2/O2
(L-L ) bathophenanthroline),12 and NaOCl/TEMPO,13 which
were successfully applied to oxidation of alcohols, failed to
convert 1 into 2. The bulkiness of 1 may hinder coordination
to Ru and hence catalytic activity. Mio et al.14 reported the
successful oxidation of 1 to 2 using RuCl3 xH2O (3 mol %)
and NaIO4 (1.5 equiv) in CHCl3/H2O under phase transfer
conditions at reflux (99% yield). Moderate selectivity to 2
was obtained by Fung et al.15 using [Cn*Ru(CF3CO2)3‚H2O]
(1 mol %, Cn* ) N,N′,N′′-trimethyl-1,4,7-triazacyclononane)
with tBuOOH (1-1.2 equiv) in CH2Cl2 at 40 °C (58% yield).
However, these methods involve the use of an expensive
oxidant/catalyst and/or unattractive conditions.
We recently discovered that for the biphasic ruthenium-
catalyzed hypochlorite R-oxidation of aliphatic ethers, a
narrow pH range (8-10) is required to achieve the best
selectivity to esters.16 The pH can be kept constant throughout
the catalytic run by either (a) use of a NaHCO3/Na2CO3
buffer solution or (b) feed-on-demand addition of HCl
(during the addition of NaOCl) and NaOH (afterward) via a
pH-stat device. The best Ru precursor proved to be (iPr4N)-
(RuO4), TPAP, which was synthesized according to the
literature.17
substrates are converted into the corresponding ketones in
high yield and selectivity when the reaction is carried out at
pH 9.5 in the presence of the appropriate buffer solution.
For simple secondary alcohols, the reactions proceed
smoothly under optimized conditions using a stoichiometric
amount of NaOCl and 0.25 mol % of ruthenium. At the end
of the reaction, the catalyst is present as RuO2 in the water
phase, and this permits the recovery of the products by simple
phase separation and evaporation of the solvent.18 We have
reduced the environmental impact of the process using
EtOAc or methyl tert-butyl ether (MTBE) instead of CH2-
Cl2 or other chlorinated solvents still commonly used in
oxidations involving RuO4. Other sources of Ru, i.e., RuCl3
and RuO2, can also be used, but in this case approximately
two times higher concentrations of Ru will be required
compared to TPAP.16 Solvent-free oxidation of 2-octanol to
2-octanone was also successfully carried out (conversion at
4 h, 99%, isolated yield 97%). Catalysis still occurs in the
organic phase, in this case the substrate itself. The effect of
pH on activity and selectivity was investigated. Oxidation
of 1 at acidic pH in the presence of TPAP (1 mol %) yielded
2 in lower selectivity than at basic pH, while the blank
reaction showed decomposition of the substrate, probably
due to deprotection. For the oxidation of 2-octanol, higher
conversions and selectivities were obtained at pH 6 with or
without Ru, in agreement with data reported by Stevens et
al.7 (Table 2). These observations suggest that the efficiency
of the process depends more on the stability of the substrate
at different pH rather than on the stability and solubility of
the catalyst. No byproducts of the oxidation of 1 to 2 could
be identified under the various conditions applied. We
assume that the major side reaction is deprotection followed
by destructive over-oxidation to CO2.
(8) Tu, Y.; Wang, Z.-X.; Shi, Y. J. Am. Chem. Soc. 1996, 118, 9806.
Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. J. Am. Chem. Soc.
1997, 119, 11235. Shu, L.; Shi, Y. Tetrahedron 2001, 57, 5213.
(9) Roldan, F.; Gonzalez, A.; Palomo, C. Carbohydr. Res. 1986, 149,
C-1. Fayet, C.; Gelas, J. Carbohydr. Res. 1986, 155, 99.
(10) Ishii, Y.; Sakaguchi, S.; Iwahama, T. AdV. Synth. Catal. 2001, 343,
393.
(11) Dijksman, A.; Marino-Gonzalez, A.; Mairata-Payeras, A.; Arends,
I. W. C. E.; Sheldon, R. A. J. Am. Chem. Soc. 2001, 123, 6826.
(12) ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A. Science 2000,
287, 1636.
(13) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis 1996,
1153.
(14) Mio, S.; Kumagawa, Y.; Soji, S. Tetrahedron 1991, 47, 2133. See
also: Baker, D. C.; Horton, D.; Tindall, C. G., Jr. In Methods in
Carbohydrate Chemistry; Whistler, R. L., BeMiller, J. N. Eds.; Academic
Press: New York, 1976; Vol. 7, p 3.
(17) Griffith, W. P.; Ley, S. V. Aldrichimica Acta 1990, 23, 13. Lee, D.
G.; Wang, Z.; Chandler, W. D. J. Org. Chem. 1992, 57, 3276.
(15) Fung, W.-H.; Yu, W.-Y.; Che, C.-M. J. Org. Chem. 1998, 63, 2873.
(16) Gonsalvi, L.; Arends, I. W. C. E.; Sheldon, R. A. Chem. Commun.
2002, 202.
(18) In a scaled-up experiment under the conditions described in Table
1, oxidation of 1 (10.4 g, 40 mmol) afforded 2 as a NMR-pure white
precipitate after solvent evaporation in 85% isolated yield (8.8 g, 34 mmol).
1660
Org. Lett., Vol. 4, No. 10, 2002

Efficient catalyst recycling was also possible. After the
organic phase was separated, RuO2 was back-extracted as
RuO4 with fresh solvent from the water phase by acidification
and addition of a few drops of NaOCl. The new organic
phase so obtained could be used directly for a new cycle.19
The results shown in Figure 1 demonstrate that there is a
Table 2. pH Tolerance and Blank Reactions in the Oxidation
of 1 to 2 and of 2-Octanol to 2-Octanone via TPAP/NaOCl
substrate
pH
TPAP (mol %)
% convc
% yieldc
1a
6.0
6.0
9.5
9.5
6.0
6.0
9.5
9.5
57
95
12
98
89
99
60
95
0
64
7
90
70
98
28
94
1.0
1.0
1.0
1.0
2-octanolb
a 1 (5 mmol), MTBE (20 mL), NaOCl 0.7 M (3 equiv dropwise over 2
h), buffer solution (5 mL), rt, 4 h. b 2-Octanol (5 mmol), EtOAc (5 mL),
NaOCl 0.7 M (1 equiv dropwise over 1 h), buffer solution (5 mL), rt, 2 h.
Buffers: NaHCO3/Na2CO3 (pH 9.5), NaH2PO4/Na2HPO4 (pH 6.0). c GC
conversions and yields, based on pure samples, 1,2,4-trichlorobenzene
internal standard.
The protocol was also applied to the oxidation of 1-octanol
3 as a model for primary alcohols. The blank reaction at pH
6 in EtOAc gave 73% conversion in 3 h, yielding 1-octanal
4 (27%), octanoic acid 5 (15%), and octyl octanoate 6 (20%).
In the presence of TPAP (1 mol %), similar conversions and
selectivities were observed at pH 6 (conversion at 3 h, 78%;
yields, 4, 25%; 5, 30%; 6, 12%) and pH 9.5 (conversion at
3 h, 70%; yields, 4, 20%; 5, 28%; 6, 8% after workup).
The use of buffer solutions proved to be more efficient
than the feed-on-demand addition of HCl/NaOH (Table 3,
Figure 1. Catalyst recycling in the oxidation of 1 (2 mmol) to 2
(not optimized). TPAP (cycle 1) 1 mol %, MTBE (10 mL), NaOCl
0.7 M (3 equiv), room temperature, 4 h, pH 9.5 (Dosimat).
small loss in activity after four cycles. We attribute this to
mechanical losses owing to the small scale of the reaction
(1, 2 mmol; TPAP, 0.02 mmol); however, the loss in
selectivity is moderate (from 83% to 72% after four cycles).
In summary, our study provides an efficient, cheap, and
recyclable catalytic method for the so far troublesome
oxidative synthesis of 2, a catalyst for asymmetric olefin
epoxidation.
Table 3. Effect of TPAP Concentration and Use of Promoters
in the Oxidation of 1 to 2 via TPAP/NaOCla
entry
promoter (mol %) TPAP (mol %) % conv % yield
Acknowledgment. This project was financed by the
Dutch Ministry of Economic Affairs under the Innovation
Oriented Projects scheme (IOP Catalysis). We thank G.-J.
ten Brink and A. Dijksman for supplying unpublished results
and for useful discussions. We also thank Catalytica for a
generous gift of 1,2:4,5-di-O-isopropylidene-â-D-fructopy-
ranose.
1
2
3
4
5
6
7
none
none
none
KBr (5)
KBr (2.5)
KBr (1)
pyridine oxide (5)
1.0
0.5
0.1
0.5
0.25
0.1
0.5
99
77
35
99
88
57
87
83
49
27
74
63
36
60
a 1 (5 mmol), MTBE (20 mL), NaOCl 0.7 M (3 equiv dropwise over 2
h), rt, 4 h. The pH was kept constant at 9.5 by feed-on-demand addition of
HCl (during the addition of NaOCl) and NaOH (afterward) via Dosimat.
Supporting Information Available: Experimental pro-
cedure for oxidations, including recycling experiments. This
material is available free of charge via the Internet at
http://pubs.acs.org.
entry 1) and should be preferred. Promoters such as KBr
and pyridine oxide (10:1 ratio to TPAP) could be used to
decrease the amount of catalyst, e.g. from 1.0 to 0.5 mol %,
without loss of activity and moderate decrease in selectivity
to 2 (Table 3, entry 4).
OL025705F
(19) Kakuda, M.; Okamoto, T.; Onozawa, T.; Kurata, H. European Patent
Appl. EP1069103, 2001.
Org. Lett., Vol. 4, No. 10, 2002
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