Efficient one-pot conversion of carbonyl compounds to their α,β-unsaturated derivatives using a recoverable, minimally fluorous organoselenium reagent

Article abstract of DOI:10.1021/ol005669p

(equation presented) A protocol for the preparation of a fluorous arylselenenyl chloride is described. This selenenyl chloride may be used for the direct α-selenation of ketones and, following oxidation and syn-elimination, formation of α,β-unsaturated carbonyl compounds. Treatment of the crude reaction mixtures with sodium metabisulfite reduces the various selenium species to the diaryl diselenide, which is then recovered in high yield by continuous fluorous extraction.

Full text of DOI:10.1021/ol005669p

ORGANIC
LETTERS
2000
Vol. 2, No. 7
989-991
Efficient One-Pot Conversion of
Carbonyl Compounds to Their
r,â-Unsaturated Derivatives Using a
Recoverable, Minimally Fluorous
Organoselenium Reagent
David Crich* and Gregory R. Barba
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
dcrich@uic.edu
Received February 15, 2000
ABSTRACT
A protocol for the preparation of a fluorous arylselenenyl chloride is described. This selenenyl chloride may be used for the direct r-selenation
of ketones and, following oxidation and syn-elimination, formation of r,â-unsaturated carbonyl compounds. Treatment of the crude reaction
mixtures with sodium metabisulfite reduces the various selenium species to the diaryl diselenide, which is then recovered in high yield by
continuous fluorous extraction.
The formal dehydrogenation of carbonyl compounds to their
R,â-unsaturated derivatives by introduction of an R-aryl-
selenyl group, followed by oxidation to a selenoxide and
eventual syn-elimination,1,2 has become a mainstay of organic
synthesis since its introduction in 1973 by the Clive,3 Reich,4
and Sharpless5 laboratories. Application of this reaction on
an industrial scale is, however, not nearly as widespread as
in academic laboratories. The reasons for this are obvious
and stem from environmental and economic factors as well
as issues relating to purification and recyclability. The
immediate byproduct of the reaction is an areneselenenic acid
(ArSeOH) which is not stable and, as demonstrated by Reich6
and Kice,7 undergoes disproportionation to the diaryl di-
selenide and the areneseleninic acid (ArSeO2H). Purification
can therefore sometimes be difficult owing to the need to
remove at least two organoselenium byproducts of widely
differing polarity. Barton and his co-workers addressed this
problem through the introduction of benzeneseleninic acid/
anhydride, a reagent that could be used in catalytic quantities
to achieve dehydrogenation of ketones.8 Unfortunately, this
method has not been adopted widely, perhaps because of
the hypervalent iodine species used as the in situ stoichio-
metric oxidant. Much more recently the Nicolaou group has
introduced polystyrene-bound organoselenium reagents to
(1) Jones, D. N.; Mundy, D.; Whitehouse, R. D. J. Chem. Soc., Chem.
Commun. 1970, 86.
(2) Sharpless, K. B.; Young, M. W.; Lauer, R. F. Tetrahedron Lett. 1973,
1979.
(3) Clive, D. L. J. J. Chem. Soc., Chem. Commun. 1973, 695.
(4) Reich, H. J.; Reich, I. L.; Renga, J. M. J. Am. Chem. Soc. 1973, 95,
5813.
(6) Reich, H. J.; Willis, W. W.; Wollowitz, S. Tetrahedron Lett. 1982,
23, 3319.
(7) Kice, J. L.; McAfee, F.; Slebocka-Tilk, H. Tetrahedron Lett. 1982,
23, 3323.
(5) Sharpless, K. B.; Lauer, R. F.; Teranishi, A. Y. J. Am. Chem. Soc.
1973, 95, 6137.
(8) Barton, D. H. R.; Godfrey, C. R. A.; Morzycki, J. W.; Motherwell,
W. B.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 1982, 1947.
10.1021/ol005669p CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/08/2000

circumvent the purification problem,9 but no mention was
made of the recyclability of these species. Here we describe
our own solution to this problem in the form of a minimally
fluorous arylselenium reagent, which, following treatment
of the crude reaction mixtures with sodium metabisulfite, is
recovered almost quantitatively as the diselenide by extrac-
tion with a water-cooled continuous extractor. We anticipate
that the ease of operation of the protocol and the high
recoverability of the reagent by a simple continuous extrac-
tion technique will facilitate the use of this type of chemistry
beyond the academic laboratory.
Table 1. Dehydrogenation of Carbonyl Compounds and
Recovery of the Fluorous Diselenide 2
The areneselenyl halides 1a and 1b were prepared from
the diselenide 2,10,11 by treatment with sulfuryl chloride, and
from the selenocyanate 3,10,11 by exposure to bromine,
respectively, followed by evaporation to dryness. The
chloride (1a) was a red crystalline solid while the bromide
(1b) was obtained in the form of dark red crystals. Both
substances were somewhat hygroscopic, and the bromide was
slowly converted to the diselenide (2) on storage under
vacuum in the ambient laboratory light.
Treatment of the steroidal enone 4 with LDA in THF
followed by the bromide 1b provided the R-arylselenoketone
5, which was not isolated but exposed at room temperature
to hydrogen peroxide. Chromatography of the crude reaction
mixture enabled isolation of the cross-conjugated dienone 6
in 70% yield. The ability of the fluorous arylselenyl groups
to take part in a typical selenation, oxidation, syn-elimination
sequence was therefore established. We next investigated a
protocol, following an early lead by Sharpless,5 in which
the ketone was simply stirred in THF with the chloride 1a
leading directly to the R-arylseleno ketone, presumably by
an acid-catalyzed enolization, followed by oxidation with
hydrogen peroxide and syn-elimination. This second protocol
was found to be operationally simpler, not requiring genera-
tion of the lithium enolate, and gave comparable, even better,
overall yields. It was, therefore, adopted as the standard
protocol.
nicely soluble in halogenated solvents and in perfluorinated
solvents, as noted previously,10,11 such that it may be
conveniently recovered by brief continuous extraction.10-12
The higher oxidation state species (ArSeOH, ArSeO2H)6,7
and their anhydrides6,7 generated in the course of the
oxidation/elimination were found to be much less soluble in
either phase and accumulated at the phase boundary in any
extraction, continuous or classical. Therefore, we turned to
in situ reduction protocols with the aim of recovering the
reagent in the form of the more soluble diselenide. With
isolated samples of the oxidized selenium byproducts we
favored brief treatment with hydrazine hydrate,13 which
wrought clean and complete conversion to the diselenide (2)
in a matter of minutes. However, fears of reaction between
the enone and hydrazine as well as of possible reduction of
the enones by diimide led us to select sodium metabisulfite14
as the in situ reductant. Thus, a protocol was developed in
which the crude reaction mixtures were treated for 1 h at
room temperature with this reagent before being subjected
to an aqueous wash. The organic layer was then partitioned
between FC-7215 and dichloromethane in the continuous
(10) Crich, D.; Hao, X. Org. Lett. 1999, 1, 269.
We next turned to recovery of the fluorous selenium
moiety. The minimally fluorous (52% F) diselenide 2 is
(11) Crich, D.; Hao, X.; Lucas, M. Tetrahedron 1999, 55, 14261.
(12) Curran has termed such “minimally” fluorous reagents “light”
fluorous reagents and has presented an alternative protocol for their recovery
involving chromatography over fluorous silica gel: Curran, D. P.; Luo, Z.
J. Am. Chem. Soc. 1999, 121, 9069.
(9) Nicolaou, K. C.; Pastor, J.; Barluenga, S.; Winssinger, N. J. Chem.
Soc., Chem. Commun. 1998, 1947.
990
Org. Lett., Vol. 2, No. 7, 2000

extractor for several hours. Distillation of the recyclable FC-
72 then yielded the diselenide 2 whereas the organic phase
yielded the enone after chromatography on silica gel.
Table 1 presents four examples of the overall procedure
involving stirring the ketone with chloride 1a and then with
hydrogen peroxide before treatment with sodium met-
abisulfite and continuous fluorous extraction.16 It will be
noted that the yields of enone are generally good, as is that
of the recovered diselenide. The final example of Table 1
was conducted with the LDA/ArSeBr protocol, but isolation
involved standard treatment with sodium metabisulfite and
continuous extraction.
Acknowledgment. We thank the NSF (CHE 9986200)
for support of this work.
OL005669P
(0.15 mL) was added dropwise, and the mixture stirred for an additional
hour. Sodium metabisulfite (5 mmol) was then added and the mixture stirred
for 1 h. The reaction mixture was then diluted with ethyl acetate (4 mL),
and the organic phase was washed with water and brine and concentrated
in vacuo to give a residue which was partitioned between CH2Cl2 (6 mL)
and FC-72 (25 mL) in the water-cooled continuous extractor11 for 2 h.
Evaporation of the FC-72 phase provided the recovered diselenide 2,
whereas the organic phase afforded the enone after filtration on silica gel.
(17) Huffman, J. W. J. Org. Chem. 1976, 41, 3847.
(18) Trost, B.; Parquette, J. R. J. Org. Chem. 1993, 58, 1579.
(19) Nakatani, K.; Takada, K.; Isoe, S. J. Org. Chem. 1993, 60, 2466.
(20) Butlin, R. J.; Linney, I. D.; Mahon, M. F.; Tye, H.; Wills, M. J.
Chem. Soc., Perkin Trans. 1 1996, 95.
(13) Rheinboldt, H.; Giesbrecht, E. Chem. Ber. 1955, 88, 666.
(14) Buehler, C. A.; Harris, J. O.; Arendale, W. F. J. Am. Chem. Soc.
1950, 72, 4953.
(15) FC-72 is a relatively inexpensive perfluorinated hydrocarbon solvent
available from 3M Speciality Chemicals Division.
(16) General Experimental Protocols: (a) Preparation of Chloride
1a. To a solution of 2 (0.25 mmol) in CCl4 (2 mL) was added SO2Cl2
(0.04 mL, 0.5 mmol), and the resulting solution stirred at room temperature
for 30 min. Evaporation to dryness then gave a red crystalline solid that
was used as such for the dehydrogenations. (b) Dehydrogenation with
1a. The ketone (0.5 mmol) and freshly prepared 1a (0.5 mmol) were stirred
in THF (2 mL) at room temperature for 24 h before 30% aqueous H2O2
(21) Bruncko, M.; Crich, D. J. Org. Chem. 1994, 59, 4239.
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