Selective rhenium-catalyzed oxidation of secondary alcohols with methyl sulfoxide in the presence of ethylene glycol, a convenient one-pot synthesis of ketals

Article abstract of DOI:10.1021/ol990755e

Formula presented Secondary alcohols are oxidized preferentially by DMSO and the catalyst ReOCl₃(PPh₃)₂ in the presence of ethylene glycol and refluxing toluene, producing the corresponding ketals. The reactions are rapid, and proceed in very good to excellent yields. The byproducts of the reaction, methyl sulfide and water, are easily removed. No epoxidation or other common side reactions were observed. This direct oxidative transformation of alcohols to the protected ketal derivatives should have broad synthetic applicability.

Full text of DOI:10.1021/ol990755e

ORGANIC
LETTERS
1999
Vol. 1, No. 5
769-771
Selective Rhenium-Catalyzed Oxidation
of Secondary Alcohols with Methyl
Sulfoxide in the Presence of Ethylene
Glycol, a Convenient One-Pot Synthesis
of Ketals
Jeffrey B. Arterburn* and Marc C. Perry
Department of Chemistry and Biochemistry MSC 3C, New Mexico State UniVersity,
P.O. Box 30001, Las Cruces, New Mexico 88003
jarterbu@nmsu.edu
Received June 22, 1999
ABSTRACT
Secondary alcohols are oxidized preferentially by DMSO and the catalyst ReOCl3(PPh3)2 in the presence of ethylene glycol and refluxing
toluene, producing the corresponding ketals. The reactions are rapid, and proceed in very good to excellent yields. The byproducts of the
reaction, methyl sulfide and water, are easily removed. No epoxidation or other common side reactions were observed. This direct oxidative
transformation of alcohols to the protected ketal derivatives should have broad synthetic applicability.
The oxidation of alcohols to carbonyl compounds is a
fundamental transformation in organic synthesis. While many
different reagents are available, there remains a constant need
for the development of new oxidants with improved chemose-
lectivity.1,2 Other desirable characteristics for a reagent are
stability, low cost, and minimal concomitant waste.3 Sul-
foxide-based Swern oxidations are frequently used to oxidize
primary and secondary alcohols,4 although this method
requires anhydrous solvents, low temperatures, an amine
base, and a strong electrophile to generate the reactive
sulfonium ion. Consideration of the hypothetical reaction of
2-propanol with methyl sulfoxide eq 1 illustrates the potential
advantages of a catalytic process, since water and methyl
sulfide are the only byproducts. The stability of methyl
sulfoxide constitutes the greatest challenge toward the
development of this catalytic process. Transition metals such
as rhenium are capable of activating sulfoxides for other
synthetically useful oxidation reactions.5 Recently, allylic and
(1) (a) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of
Organic Compounds; London, 1981. (b) Hudlucky, M. Oxidations in
Organic Chemistry; American Chemical Society: Washington, D.C., 1990.
(c) Parshall, G. W.; Ittel, S. D. Homogeneous Catalysis, 2nd ed.; John Wiley
& Sons: New York, 1992. (d) Naota, T.; Takaya, H.; Murahashi, S.-I. Chem.
ReV. 1998, 98, 2599.
(2) A variety of metals catalyze the oxidation of alcohols with hydrogen
peroxide (a) Clerici, M. G. Stud. Surf. Sci. Catal. 1993, 78, 21. The high
reactivity of peroxides can lead to other reactions such as the following:
alkene epoxidation [(b) Trost, B. M.; Masuyama, Y. Tetrahedron Lett. 1984,
25, 173], oxidative cleavage of diols [(c) Ishii, Y.; Yamawaki, K.; Yoshida,
T.; Ura, T.; Ogawa, M. J. Org. Chem. 1987, 52, 1868; (d) Kaneda, K.;
Kawanishi, Y.; Jitsukawa, K.; Teranishi, S. Tetrahedron Lett. 1983, 24,
5009], and ether oxidation [(e) Murray, R. W.; Iyanar, K.; Chen, J.; Wearing,
J. T. Tetrahedron Lett. 1995, 36, 6415; (f) Zauche, T. H.; Espenson, J. H.
Inorg. Chem. 1998, 37, 6827; (g) Espenson, J. H.; Zhu, Z.; Zauche, T. H.
J. Org. Chem. 1999, 64, 1191].
(3) Aerobic oxidations selective for primary alcohols have been catalyzed
by copper [(a) Chaudhuri, P.; Hess, M.; Flo¨rke, U.; Wieghardt, K. Angew.
Chem., Int. Ed. Engl. 1998, 37, 2217], palladium [(b) Peterson, K. P.;
Larock, R. C. J. Org. Chem. 1998, 63, 3185; (c) Nishimura, T.; Onoue, T.;
Ohe, K.; Uemura, S. Tetrahedron Lett. 1998, 39, 6011], and ruthenium
[(d) Hanyu, A.; Takezawa, E.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett.
1998, 39, 5557].
(4) Tidwell, T. T. Synthesis 1990, 857.
(5) (a) Arterburn, J. B.; Nelson, S. L. J. Org. Chem., 1996, 61, 2260.
(b) Arterburn, J. B.; Perry, M. C. Tetrahedron Lett. 1996, 37, 7941. (c)
Arterburn, J. B.; Perry, M. C.; Nelson, S. L.; Dible, B. R.; Holguin, M. S.
J. Am. Chem. Soc. 1997, 119, 9309.
(6) Lorber, C. Y.; Pauls, I.; Osborn, J. A. Bull. Soc. Chim. Fr. 1996,
133, 755.
10.1021/ol990755e CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/05/1999

Table 1. Rhenium-Catalyzed Alcohol Oxidation with DMSO and Ethylene Glycol7
benzylic alcohols were catalytically oxidized with sulfoxides
using cis-dioxomolybdenum(VI) complexes.6 In this com-
munication, we describe a new catalytic rhenium-ethylene
glycol system which selectively oxidizes secondary alcohols
with methyl sulfoxide, and conveniently produces the cor-
responding ethylene ketals.
preferential reactivity of secondary alcohols in this system
was evident from the reaction of diol 1, which was
completely oxidized to ketone 2 after 1 h, 89% yield.
(CH3)2CH(OH) + Me2SO f
(CH3)2C(O) + H2O +Me2S (1)
When our investigation was extended to include less-
hindered alcohol substrates, we found that ketals were
obtained as the major products from further reaction of the
ketones with ethylene glycol under the mild Lewis acidic
conditions Table 1.7 The oxidation of 2-dodecanol using the
standard conditions produced the ketal and ketone in 86%
and 5% isolated yields, respectively (entry 1). The oxidation
We had initially observed low yields of ketone products
from the catalytic oxidation of secondary alcohols with
ReOCl3(PPh3)2 and methyl sulfoxide in refluxing toluene and
found that primary alcohols were even less reactive under
these conditions. Interestingly, a dramatic increase in reactiv-
ity resulted from the addition of ethylene glycol. The
770
Org. Lett., Vol. 1, No. 5, 1999

of the primary alcohol 1-dodecanol to the acetal was
significantly slower and required additional methyl sulfoxide,
ethylene glycol, and a longer reaction time (entry 2).8
Alcohols were selectively oxidized in the presence of alkenes,
and no oxidative cyclization typical of rhenium(VII) trioxo
complexes occurred with the diene-ol substrate (entry 3).9
The phenol group was also unaffected during the oxidative
ketalization of the secondary alcohol in â-estradiol (entry
4).
The oxidation of benzyl alcohol under these conditions
was problematic due to the competing formation of ether
byproducts which result from ionization to the benzylic
carbocation. Consistent with this explanation, the 4-nitro-
substituted analogues were oxidized in high yield without
producing the ether byproducts (entries 6 and 7). The yield
of acetal from the oxidation of benzyl alcohol was dramati-
cally improved by the addition of a small amount of the mild
base 2,4,6-collidine as a buffer (method B, entry 5). The
yields of ketals from the oxidation of secondary alkyl
alcohols were also slightly improved (entries 8 and 9).
Epimerization of the R-position occurred during the reaction
of menthol, producing a 6:1 mixture of menthone:isomen-
thone ketals (entry 8).
The direct oxidative transformation of alcohols to the
protected ketal derivative is unprecedented in the alcohol
oxidation literature to the best of our awareness, and this
procedure should have broad synthetic applicability. As
further evidence of the synthetic utility of this method, we
carried out a one-step synthesis of the olive fly ketal 4 by
directly oxidizing 1,5,9-nonanetriol 3. Here preferential
intramolecular ketal formation occurred, giving the volatile
spiro ketal product in 57% isolated yield.10
The dramatic difference in reactivity due to ethylene glycol
implicates its possible role as a chelating ligand.11 Chelating
ligands are known to favor the formation of cis-dioxo d2
octahedral metal complexes, which are typically more
reactive than the trans isomers.12,13 cis-Dioxorhenium(VII)
complexes containing the chelating hydridotris(1-pyrazolyl)-
borate ligand are known to stoichiometrically oxidize
coordinated alcohols.14 The faster rate for the oxidation of
secondary alcohols is consistent with a mechanism where
decomposition of a metalloester intermediate is the rate-
determining step.2b Mechanistic investigations, and further
development of synthetic applications are currently in
progress.
(7) General Procedure. Method A. The alcohol (1 mmol), ethylene
glycol (4 mmol), DMSO (2.1 mmol), and Re(O)Cl3(PPh3)2 (0.05 mmol) in
toluene (5 mL) was refluxed using a Dean-Stark apparatus. Additional
portions of ethylene glycol (8 mmol) were added to the reaction mixture
after 1 h and 3 h. After 5 h, the reaction mixture was washed with NaHCO3
and H2O, dried MgSO4, and purified by chromatography or bulb-to-bulb
distillation. Method B. 2,4,6-Collidine (3.3 µL, 0.025 mmol) was also
included. Ketones were efficiently converted to the ketals when they were
added to the reaction mixture.
(8) Ethylene glycol was consumed slowly during the reaction.
(9) (a)Tang, S.; Kennedy, R. M. Tetrahedron Lett. 1992, 33, 5303. (b)
McDonald, F. E.; Singhi, A. D. Tetrahedron Lett. 1997, 38, 7683. (c) Towne,
T. B.; McDonald, F. E. J. Am. Chem. Soc. 1997, 119, 6022. (d) Sinha, S.
C.; Keinan, E.; Sinha, S. C. J. Am. Chem. Soc. 1998, 120, 9076.
(10) Reddy, G. B.; Mitra, R. B. Synth. Commun. 1986, 16, 1723.
(11) Rhenium(VII) trioxo diol complexes of the tertiary diol pinacol have
been synthesized: Edwards, P. G.; Jokela, J.; Lehtonen, A.; Sillanpa¨a¨, R.
J. Chem. Soc., Dalton Trans. 1998, 3287.
Acknowledgment. The authors thank the USAMRC
(12) Demachy, I.; Jean, Y. New J. Chem. 1996, 20, 53.
(13) Reaction mixtures containing 1,3-propanediol, a ligand with a larger
“bite angle”, were not effective for oxidizing alcohols. Interestingly, diol 1
also reacted with the catalyst and DMSO in the absence of ethylene glycol
to produce ketone 2. This observation is consistent with the enhanced
chelating ability of this diol relative to 1,3-propanediol due to the Thorpe-
Ingold effect.
DAMD17-97-1-7120 for financial support.
Supporting Information Available: Detailed descrip-
tions of experimental procedures. This material is available
free of charge via the Internet at http://pubs.acs.org.
(14) (a) DuMez, D. D.; Mayer, J. M. Inorg. Chem. 1995, 34, 6396. (b)
DuMez, D. D.; Mayer, J. M. Inorg. Chem. 1998, 37, 445.
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