Catalytic allylic oxidation with a recyclable, fluorous seleninic acid

Article abstract of DOI:10.1021/ol036501h

In conjunction with iodoxybenzene as reoxidant perfluorooctylseleninic acid catalyzes the allylic oxidation of alkenes to enones in trifluoromethylbenzene at reflux in moderate to good yield. After a reductive workup with sodium metabisulfite, the catalyst is recovered by fluorous extraction in the form of bis(perfluorooctyl) diselenide, which, itself, serves as a convenient catalyst precursor.

Full text of DOI:10.1021/ol036501h

ORGANIC
LETTERS
2004
Vol. 6, No. 5
775-777
Catalytic Allylic Oxidation with a
Recyclable, Fluorous Seleninic Acid
David Crich* and Yekui Zou
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
dcrich@uic.edu
Received December 24, 2003
ABSTRACT
In conjunction with iodoxybenzene as reoxidant perfluorooctylseleninic acid catalyzes the allylic oxidation of alkenes to enones in
trifluoromethylbenzene at reflux in moderate to good yield. After a reductive workup with sodium metabisulfite, the catalyst is recovered by
fluorous extraction in the form of bis(perfluorooctyl) diselenide, which, itself, serves as a convenient catalyst precursor.
The allylic oxidation of alkenes is a reaction of fundamental
importance from the research laboratory to the plant.1 As
such it is undergoing continual refinement with a view to
the development of more environmentally friendly, efficient,
and selective processes.2 Selenium dioxide has long been a
favorite reagent for this transformation3 and also a target for
incorporation into catalytic cycles.4 In 1985 it was reported
that 2-pyridylseleninic acid (1), in contrast to benzene-
seleninic acid (2), was an effective catalyst for the allylic
oxidation of alkenes to alkenones in the presence of
iodoxybenzene as stoichiometric reagent.5 Subsequently,
more electron-deficient arylseleninic acids, in particular
pentafluorobenzeneseleninic acid (3) and 2-pyridylseleninic
acid N-oxide (4), were shown to be more effective allylic
oxidation catalysts.6 Unfortunately these suffered from a
number of unsatisfactory characteristics, not the least of
which was a tendency toward explosive decomposition. We
reasoned that the attachment of a perfluoroalkyl, or fluorous,
chain directly to selenium would enable the formation of a
highly electron-deficient seleninic acid catalyst that would
not suffer from the same problems as the aromatic variants.
We report here that this is indeed the case and that
perfluorooctylseleninic acid (5) is an effective catalyst for
the oxidation of alkenes to enones when used in conjunction
with a hypervalent iodine-based oxidant.
(1) Reviews: (a) Andrus, M. B.; Lashley, J. C. Tetrahedron 2002, 58,
845. (b) Sheldon, R. A. In Fine Chemicals Through Heterogeneous
Catalysis; Sheldon, R. A., Van Bekkum, H., Eds.; Wiley-VCH: Weinheim,
Germany, 2001; p 519. (c) Grennberg, H.; Backvall, J. E. In Transition
Metals for Organic Synthesis; Beller, M., Bolm, C., Eds.: Wiley-VCH:
Weinheim, Germany, 1998; Vol. 2, p 200. (d) Schlingloff, G.; Bolm, C. In
Transition Metals for Organic Synthesis; Beller, M., Bolm, C., Eds.: Wiley-
VCH: Weinheim, Germany, 1998; Vol. 2, p 193. (e) Bulman Page, P. C.;
McCarthy, T. J. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.:
Pergamon: Oxford, UK, 1991; Vol. 7, p 83. (f) Eames, J.; Watkinson, M.
Angew. Chem., Int. Ed. 2001, 40, 3567.
(2) Recent work: (a) Yu, J.-Q.; Corey, E. J. J. Am. Chem. Soc. 2003,
125, 3232.
(3) Hoekstra, W. J. In EROS; Paquette, L. A., Ed.: Wiley: Chicester,
UK, 1995; Vol. 6, p 4437.
(4) (a) Umbreit, M. A.; Sharpless, K. B. J. Am. Chem. Soc. 1977, 99,
5526. (b) For a discussion of allylic oxidation with seleninic acids see:
Ley, S. V. In Organoselenium Chemistry; Liotta, D., Ed.: Wiley: New
York, 1987; p 163.
The catalyst (5) is readily assembled in a simple two-step
protocol from perfluorooctyl iodide and dibutyl diselenide
10.1021/ol036501h CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/06/2004

with the aid of Rongalite. As expected from the recent work
of Wakselman,7 this affords perfluorooctyl butyl selenide (6)
in good yield. Treatment with hydrogen peroxide then affords
the selenoxide, which undergoes syn-elimination to give
perfluorooctylseleninic acid (7), which then suffers further
oxidation to the desired product (5) (Scheme 1). Although
washing with water.10 After removal of the volatiles the
organic phase was partitioned between dichloromethane (3.0
mL) and perfluorohexanes (10.0 mL) in a water-cooled
continuous extractor11 for 3 h. Evaporation of the fluorous
phase returned the catalyst in the form of the diselenide 8,
whereas chromatography of the organic layer over silica gel
yielded the enone. A number of oxidations were conducted
in this manner, with the results reported in Table 1.
Scheme 1. Preparation of the Fluorous Selininic Acid 5
Table 1. Allylic Oxidation with Catalytic 5 and Iodoxybenzene
diethyl diselenide would have served admirably in place of
dibutyl diselenide in this synthesis and maximized atom
efficiency, dibutyl diselenide was preferred owing to its less
volatile, less malodorous nature, but one that nevertheless
is coupled to the formation of a single gaseous byproduct.
The seleninic acid 5 generated in this manner was a stable
but somewhat insoluble, amorphous white stable solid with
a melting point of 135-137 °C and a high-resolution mass
structure consistent with the assigned spectrum. Although 5
was insoluble in most organic solvents and fluorous hydro-
carbons, it dissolved readily in hot trifluoromethylbenzene
(benzotrifluoride),8 which was selected, therefore, as the
solvent of choice for the oxidation protocol. Importantly,
it shows no tendency toward explosion, at least in our
laboratory.
3â-Cholesteryl benzoate served as a model substrate with
which to survey allylic oxidation by means of a catalytic
quantity of 5 and a range of stoichiometric reoxidants. These
included hydrogen peroxide, tert-butyl hydroperoxide, m-
CPBA, and iodoxybenzene.9 Of these the latter gave the
cleanest overall conversion of alkenes to enones with the
mimimum formation of byproducts. A protocol was therefore
developed in which the olefin (1 mmol), iodoxybenzene (3
mmol), and 5 (0.1 mmol) were heated to reflux with stirring
under nitrogen in benzotrofluoride (10 mL) until completion
(Scheme 2). Workup involved addition of solid sodium
It is noteworthy that none of the oxidations reported in
Table 1 are complicated by the issue of allylic transposition.
The chemistry therefore closely parallels that of selenium
Scheme 2. Allylic Oxidation with Catalytic 5 and
Iodoxybenzene
(6) Barton, D. H. R.; Wang, T.-L. Tetrahedron Lett. 1994, 35, 5149
(7) Magnier, E.; Vit, E.; Wakselman, C. Synlett 2001, 1260.
(8) (a) Ogawa, A.; Curran, D. P. J. Org. Chem. 1997, 62, 450. (b) Maul,
J. J.; Ostrowski, P. J.; Ublacker, G. A.; Linclau, B.; Curran, D. P. Top.
Curr. Chem. 1999, 206, 79.
(9) For the first use of iodoxybenzene as stoichiometric oxidant in
conjunction with an organoselenium catalyst see: Barton, D. H. R.;
Morzycki, J. W.; Motherwell, W. B.; Ley, S. V. J. Chem. Soc., Chem.
Commun. 1981, 1044.
(10) The insertion of a reduction into the workup is to facilitate recovery
of the fluorous reagentsdiselenide 8 dissolves readily in organic and
fluorous solvents whereas the amorphous seleninic acid is poorly soluble
and so not accessible to an extractive workup and separation.
(11) Crich, D.; Hao, X.; Lucas, M. Tetrahedron 1999, 55, 14261.
metabisulfite (1 mmol), followed by stirring at room tem-
perature for 3 h before dilution with ethyl acetate and
(5) Barton, D. H. R.; Crich, D. Tetrahedron 1985, 41, 4359.
776
Org. Lett., Vol. 6, No. 5, 2004

dioxide and accordingly, in line with current mechanistic
thinking,12 we postulate a mechanism involving an initial
ene reaction followed by a 2,3-sigmatropic rearrangement
(Scheme 3). At this stage it is not possible to determine the
Scheme 4. Oxidation of Cholesteryl Benzoate by the
Diselenide and PhIO2
Scheme 3. Probable Mechanism for Oxidation by 5 and
PhIO2
are reported to catalyze the epoxidation of alkenes when used
in conjunction with 60% hydrogen peroxide.15,16 This dif-
ference in reactivity, allylic oxidation vs epoxidation, may
be a function of the more electron-deficient selenium in 5,
or may arise from the different reoxidants employed. The
formation of perseleninic acids with hydrogen peroxide as
oxidant, which presumably accounts for the epoxidation
reaction, is obviously not possible when iodoxybenzene is
employed as reoxidant. Unfortunately, when hydrogen
peroxide was employed as oxidant in conjunction with 5
complex reaction mixtures were obtained: similar results
were observed with 5 and tert-butyl hydroperoxide.
mode of oxidation of the rearranged selenous ester to the
final product: both direct oxidation and oxidation of the
liberated allylic alcohol can be envisaged. Similarly, it is
not possible at the present time to determine whether the
oxidation is occurring via the acid 5, its anhydride, or a mixed
anhydride of 5 and the corresponding seleninic acid.
Where regiochemistry is an issue Guillemonat’s rules13
for allylic oxidation by selenium dioxide are shadowed. For
example, 1-phenylcyclohexene (11) undergoes oxidation at
the more hindered end of the alkene; geranyl acetate (15)
selectively gave the 8E-aldehyde (16), again in line with
precedent.5 Interestingly, oxidation of the 3â-cholesteryl
benzoate (9) yielded only the 4-one (10) whereas oxidation
of the same substrate by 1 resulted in a 3.7:1 mixture of the
4-one and the corresponding 7-one. The oxidation of 3â-
cholesteryl benzoate by selenium dioxide is not a clean
reaction and affords 4â-hydroxy-3â-cholesteryl benzoate in
approximately 30% yield.14
In closing we stress that the chemistry described herein
differs significantly from that of most fluorous reagents
developed to date17 insofar as it takes direct advantage of
the powerfully electron-drawing nature of the fluorous chain,
rather than interposing a spacer group. We anticipate the
development of further useful reagents based on this
concept.18
The workup protocol devised involves a reduction step.
This is necessary because of the somewhat insoluble nature
of 5 in typical organic and fluorous solvents, which hampers
direct recovery of the catalyst. As this protocol returns the
catalyst in the form of the diselenide, it was necessary for
the purposes of recycling to demonstrate the ability of this
substance to serve as catalyst precursor. In the event,
replacement of 5 by the diselenide in a typical oxidation
proceeded according to the established pattern (Scheme 4).
It is of some interest to note the difference between catalyst
5 and the related fluorous seleninic acids 25 and 26,
generated in situ from the butyl selenides 23 and 24, which
Acknowledgment. We thank the NSF (CHE 9986200)
for support of this work.
Supporting Information Available: Experimental details
for the preparation of 5 and for the allylic oxidation protocol.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL036501H
(15) (a) Betzemeier, B.; Lhermitte, F.; Knochel, P. Synlett 1999, 489.
(b) ten Brink, G.-J.; Vis, M.; Arends, I. W. C. E.; Sheldon, R. A.
Tetrahedron 2002, 58, 3977.
(16) The 3,5-disubstituted system also catalyzes the Baeyer-Villiger
(12) (a) Singleton, D. A.; Hang, C. J. Org. Chem. 2000, 65, 7554. (b)
Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc, 1972, 94, 7154.
(13) (a) Guillemonat, A. Ann. Chim. 1939, 11, 143. (b) Fieser, L. F.;
Fieser, M. In Reagents for Organic Synthesis; Wiley: New York, 1967;
Vol. 1, p 992.
(14) Vigier, A.; Marquet, A.; Barton, D. H. R.; Motherwell, W. B.; Zard,
S. Z. J. Chem. Soc., Perkin Trans. 1 1982, 1937.
oxidation of cyclobutanone.15b
(17) For a collection of articles on fluorous reagents and catalysts see:
Curran, D. P.; Gladysz, J. A., Eds. Tetrahedron 2002, 58, 3823.
(18) In a similar vein we have also reported the development of a fluorous
version of borane dimethyl sulfide in which the fluorous chain serves the
dual purposes of facilitating purification/recycling and of rendering the
borane air stable: Crich, D.; Neelamkavil, S. Org. Lett. 2002, 4, 4175.
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