An alternative to the Swern oxidation

Article abstract of DOI:10.1016/S0040-4039(02)02004-X

A variety of alcohols have been oxidized under mild conditions by the DMSO-Ph₃P·X₂ complexes. The reaction does not produce any Pummerer product. A mechanism for the reaction is proposed.

Full text of DOI:10.1016/S0040-4039(02)02004-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8355–8357
An alternative to the Swern oxidation
Alakesh Bisai, M. Chandrasekhar and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 27 June 2002; revised 29 August 2002; accepted 13 September 2002
Abstract—A variety of alcohols have been oxidized under mild conditions by the DMSO–Ph3P·X2 complexes. The reaction does
not produce any Pummerer product. A mechanism for the reaction is proposed. © 2002 Elsevier Science Ltd. All rights reserved.
The oxidation of alcohols to the corresponding car-
bonyl compounds is a very important and frequently
used transformation in organic synthesis.1 One of the
most common methods for this oxidation is via acti-
vated DMSO (Swern oxidation),2,3 which involves a
variety of electrophilic reagents as activators such as
oxalyl chloride,4 acid anhydrides,5 phosgene,6
bis(trichloromethyl)carbonate,7 cyanuric chloride,8 and
others.9 The reaction proceeds via alkoxysulfonium
salts that react with a base to give the carbonyl com-
pound and dimethyl sulfide. The major disadvantage of
the reaction is the formation of methylthioalkyl ethers
as a by-product due to the Pummerer rearrangement of
the alkoxysulfonium ylid. Amongst all activators, oxa-
lyl chloride was found to be the best as high yields of
carbonyl compounds were obtained with minimal Pum-
merer product. Although DMSO–oxalyl chloride is
routinely used, the method is still associated with some
disadvantages such as a violent reaction during the
formation of the ylid and toxicity associated with
vapors of the latter. While working on the reaction of
activated DMSO with epoxides and other strained
rings,10 we discovered that triphenylphosphine dibro-
mide (Ph3P·Br2)11 and dichloride (Ph3P·Cl2)12 in combi-
nation with DMSO are good alternatives to the
classical Swern oxidation. Details of this work are
described in this paper. Based on a 31P NMR study of
the reagent, we also propose a mechanism for the
reaction.
in a 98% isolated yield (entry 1). Similarly, the use of
Ph3P·Cl2 gave the product in high yield (entry 1).
However, the oxidation did not proceed when Ph3P·I2
was used. In order to show the scope of the reaction, a
variety of alcohols was oxidized with these reagents and
the results are summarized in Table 1. All kinds of
alcohols such as primary, secondary, allylic, and benz-
ylic alcohols could be oxidized to carbonyl compounds
in high yields. A noteworthy feature of the reaction is
that an alcohol having a sulfur atom in the molecule
could also be oxidized in a reasonably good yield (entry
8). The oxidation could also be carried out in a
molecule having silyl ethers which were inert to these
conditions (entries 22 and 23). Although ethers are
known to be cleaved13 with Ph3P·Br2, we did not
observe any such cleavage under our oxidation condi-
tions (entries 22–26). Similarly, the reagent is known to
convert alcohols into halides;14 however, we did not
observe any halo compounds under our reaction
conditions.
In order to see whether we would obtain any Pummerer
product and to understand the mechanism, the oxida-
tion of 2-tert-butyldimethylsilyloxy-1-phenylethanol
(entry 22) was tried at different temperatures. At −78,
−70, and −60°C, the reaction was complete and a high
yield (ꢀ95%) of the oxidized product was obtained. On
increasing the temperature to −50, −40, and −30°C, the
At the outset, 1-phenyl-1-butanol was treated with a
reagent prepared from DMSO and Ph3P·Br2 in CH2Cl2
at −78°C followed by Et3N under the conditions of the
Swern oxidation (Scheme 1). The ketone was obtained
* Corresponding author. Fax: 91-512-597436; e-mail: vinodks@
iitk.ac.in
Scheme 1. Proposed mechanism for oxidation of alcohols.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02004-X

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A. Bisai et al. / Tetrahedron Letters 43 (2002) 8355–8357
Table 1. Oxidation of alcohols to ketones
yield dropped to 85, 64, and 13%, respectively. In all
these cases, the lower yield was due to incomplete
oxidation and unreacted alcohol was recovered. It was
observed that there was no reaction at −20 and 0°C and
the starting material was recovered in a quantitative
manner. It was gratifying to know that even at these
temperatures, no Pummerer product was formed. Based
on a 31P NMR spectrum of a mixture of DMSO and
Ph3P·Cl2 in CD2Cl2 at −55°C, it is proposed that the
reaction does not proceed via the chlorodimethyl sulfide
ion as in the classical Swern oxidation (no signal at l 27
for Ph3PꢀO), instead a signal at l 46 was seen and was
assigned to species 1.15 There was no change in the
spectrum when the sample was warmed to room tem-
perature. It was also noted that there was not much
change in the 31P NMR spectrum on addition of an
alcohol to the reagent. No change in the 31P NMR
signal could be seen because of a similar environment
to the phosphorus in all the species. It was assumed
that the species 1 might be undergoing an irreversible
change at the higher temperatures (−20°C to rt),
because of which oxidation is not observed at these
temperatures. However, when 1 was prepared and
treated with an alcohol at −78°C, dimethylalkoxysulfo-
nium salt 2 is assumed to be formed, which on treat-
ment with
a base, decomposes to the carbonyl
compound, Me2S, and Ph3PꢀO (l 27 in 31P NMR).
In conclusion, we have described a mild method for the
oxidation of alcohols using DMSO–Ph3P·Cl2 and
DMSO–Ph3P·Br2. We also propose a suitable mecha-
nism for the reaction. It was observed that some func-

A. Bisai et al. / Tetrahedron Letters 43 (2002) 8355–8357
8357
tional groups, which could react with these reagents,
remained unaffected under the reaction conditions.
3. For a comparative study, see: Omura, K.; Swern, D.
Tetrahedron 1978, 34, 1651.
4. (a) Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org.
Chem. 1978, 43, 2480; (b) Singaram, B.; Chrisman, W.
Tetrahedron Lett. 1997, 38, 2053.
General procedure for oxidation reactions. DMSO (3
mmol) was added to a solution of PPh3X2 (1.5 mmol)
in CH2Cl2 (6 mL) was cooled at −78 °C. The color of
the solution turned yellow when PPh3Br2 was used and
it was milky white with PPh3Cl2. After one hour, 1
mmol of an alcohol solution in CH2Cl2 (2 mL) was
added and the reaction mixture was stirred at the same
temperature for 15 min when 3 mmol of Et3N were
added. The reaction mixture was allowed to warm to rt
(2 h). Most of the CH2Cl2 was removed in vacuo, and
a 1:1 mixture of Et2O and n-hexane was added to the
flask in order to precipitate Ph3PꢀO, which was filtered
off. The filtrate was evaporated and the crude product
was purified by column chromatography over silica gel
to provide pure ketones in high yields (Table 1). All the
carbonyl compounds are either commercially available
or known in the literature. They were characterized by
the usual spectral data and compared with authentic
samples.
5. (a) Omura, K.; Sharma, A. K.; Swern, D. J. Org. Chem.
1976, 41, 957; (b) Amon, C. M.; Banwell, M. G.; Gravatt,
G. L. J. Org. Chem. 1987, 52, 4851; (c) Kawada, K.;
Gross, R. S.; Watt, D. S. Synth. Commun. 1989, 19, 777.
6. (a) Barton, D. H. R.; Garner, B. J.; Wightman, R. H. J.
Chem. Soc. 1964, 1855; (b) Takano, S.; Inomata, K.;
Tomita, S.; Yanase, M.; Samizu, K.; Ogasawara, K.
Tetrahedron Lett. 1988, 29, 6619.
7. Palomo, C.; Cossio, F. P.; Ontoria, J. M.; Odriozola, J.
M. J. Org. Chem. 1991, 56, 5948.
8. De Luca, L.; Giacomelli, G.; Porcheddu, A. J. Org.
Chem. 2001, 66, 7907.
9. For other related methods, see: (a) Corey, E. J.; Kim, C.
U.; Takeda, M. Tetrahedron Lett. 1972, 4339; (b) Taber,
D. F.; Amedio, J. C., Jr.; Jung, K.-Y. J. Org. Chem.
1987, 52, 5621.
10. (a) Raina, S.; Bhuniya, D.; Singh, V. K. Tetrahedron
Lett. 1992, 33, 6021; (b) Raina, S.; Singh, V. K. Tetra-
hedron 1995, 51, 2467.
11. For the structure of Ph3P·Br2, see: Bricklebank, N.; God-
frey, S. M.; Mackie, A. G.; McAuliffe, C. A.; Pritchard,
R. G. J. Chem. Soc., Chem. Commun. 1992, 355.
12. For the structure of Ph3P·Cl2, see: Godfrey, S. M.;
McAuliffe, C. A.; Pritchard, R. G.; Sheffield, J. M.
Chem. Commun. 1998, 921.
Acknowledgements
We thank the CSIR (Government of India) for funding
our research.
References
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1. For a review, see: Haines, A. H. Methods for the Oxida-
tion of Organic Compounds; Academic Press: New York,
1988.
2. For reviews on Swern oxidation, see: (a) Mancuso, A. J.;
Swern, D. Synthesis 1981, 165; (b) Tidwell, T. T. Org.
React. 1990, 39, 297.
15. The presence of Ph3P·Cl2 was ruled out as there was no
peak at l 65 in the 31P NMR.