Surface-mediated reactions. 7. Unsupported reagents

Article abstract of DOI:10.1021/ol990823x

(equation presented) Some solid reagents traditionally supported on silica gel or alumina are also effective as heterogeneous reactants in the absence of a support. Moist magnesium monoperoxyphthalate (MMPP), either suspended in CH₂Cl₂ or solventless, is a convenient alternative to peroxycarboxylic acids for oxidation of sulfides and epoxidation of alkenes. The latter reaction exhibits an unusual order of reactivity: trisubstituted > disubstituted > tetrasubstituted. Unsupported moist Ca(OCl)₂ and OXONE are also effective oxidants.

Full text of DOI:10.1021/ol990823x

ORGANIC
LETTERS
1
999
Vol. 1, No. 6
03-904
Surface-Mediated Reactions. 7.
Unsupported Reagents1
9
Christopher J. Foti, John D. Fields, and Paul J. Kropp*
Department of Chemistry, UniVersity of North Carolina,
Chapel Hill, North Carolina 27599-3290
kropp@unc.edu
Received July 16, 1999
ABSTRACT
Some solid reagents traditionally supported on silica gel or alumina are also effective as heterogeneous reactants in the absence of a support.
Moist magnesium monoperoxyphthalate (MMPP), either suspended in CH Cl or solventless, is a convenient alternative to peroxycarboxylic
acids for oxidation of sulfides and epoxidation of alkenes. The latter reaction exhibits an unusual order of reactivity: trisubstituted > disubstituted
tetrasubstituted. Unsupported moist Ca(OCl) and OXONE are also effective oxidants.
2
2
>
2
The magnesium salt of monoperoxyphthalic acid (MMPP)
is a commercially available alternative to the oxidant
m-chloroperoxybenzoic acid (MCPBA) that is safer to handle
2 2
Thus stirring a solution of sulfide 1 in CH Cl with MMPP
supported on moistened alumina readily afforded sulfoxide
2 in excellent yield with no observable over-oxidation to
5
(
e.g., can be shipped by air) and, unlike MCPBA, does not
sulfone 3 (Table 1).
2,3
require assaying for stoichiometric use. It has received
relatively little use, however, because it is only soluble in
very polar solvents, thus usually necessitating the use of
aqueous conditions.
As with silica gel, a small amount of water is required.
However, the silica gel or alumina support is not needed:
a stirred suspension of solid MMPP, moistened with water,
6
in CH
2
Cl
2
readily afforded sulfoxide 2 (Table 1). Similar
results were obtained with moist MMPP under solvent-free
conditions with the aid of microwave heating. Thus neither
an adsorbent nor a solvent is needed!
Recently it was reported that adsorption of MMPP onto
moist silica gel allows oxidation of sulfides to sulfoxides to
4
Moist MMPP is a convenient alternative to MCPBA. In
addition to the greater safety in handling and ease of use of
MMPP, the product can be isolated by simple filtration
through Celite and removal of the solvent, avoiding the
be performed heterogeneously in CH
2
Cl
2
. We have observed
similar behavior with MMPP supported on moist alumina.
(
1) Part 6: Kropp, P. J.; Breton, G. W.; Craig, S. L.; Crawford, S. D.;
Durland, W. F., Jr.; Jones, J. E., III; Raleigh, J. S. J. Org. Chem. 1995, 60,
146-4152.
2) (a) Brougham, P.; Cooper, M. S.; Cummerson, D. A.; Heaney, H.;
4
(
(5) To provide qualitative rate data, oxidations were terminated prior to
total conversion. For preparative purposes, complete oxidation can be
effected by using longer reaction times or employing a small excess of
oxidant.
Thompson, N. Synthesis 1987, 1015-1016. (b) Heaney, H. Aldrichimica
Acta 1993, 26, 35-45, and references therein.
(3) MMPP is supplied in 80% pure form, while MCPBA is available
only in several purity ranges, including 50-55%, 57-86%, and 70-75%.
(6) The concentration of water is critical. The amounts shown in Table
1 have been qualitatively optimized.
(
4) Ali, M. H.; Stevens, W. C. Synthesis 1997, 764-768.
1
0.1021/ol990823x CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/12/1999

Table 1. Oxidation of Sulfide 1a
Table 3. Epoxidation of Cyclohexenes 4 with MMPP in
Solutiona
yield, %b
yield, %b
oxidant
adsorbent
water, µL
time, h
1
2
3
alkene
time, h
4
5
MMPP
MMPP
MMPP
MMPP
MMPP
Ca(OCl)2
OXONE
NaIO4d
Al2O3
Al2O3
12
2
12
2
c
3
98
7
97
9
500
91
4a
4b
4c
7
4
3
8
2
5
91
90
88
50
50
50
17
25
88
95
80
81
3
2
7
3
2
a
Conducted with 1 mmol of alkene 4 and 0.5 mmol of MMPP in 95%
ethanol according to the procedure of Gillard, J. R.; Newlands, M. J.;
Bridson, J. N.; Burnell, D. J. Can. J. Chem. 1991, 69, 1337-1343.
Determined by H NMR analysis relative to diphenylmethane as an internal
12
16
100
4
2
b
1
standard.
a
Conducted at 25 °C by treating a solution of 1.0 mmol of sulfide 1 in
2
5
mL of CH2Cl2 with 2.5 g of Fisher A540 alumina (pH 9, 210 m /g), if
used, and 0.5 mmol of oxidant that had been moistened with the indicated
b
1
amount of water. Determined by H NMR analysis relative to diphenyl-
behavior analogous to MMPP as unsupported reagents (Table
c
methane as an internal standard. Conducted solvent-free by microwave
heating for 40 s at 50% power of 0.5 mmol of MMPP moistened with 50
µL of water and to which 1.0 mmol of sulfide 1 had been adsorbed. 1.7
1
). However, not all solid reagents have the requisite physical
properties to serve as unsupported heterogeneous reactants.
Moist NaIO , another oxidant of sulfides when supported
d
mmol.
4
9
on silica gel or alumina, afforded no oxidation of sulfide 1
as an unsupported reagent.
tedious extraction with aqueous base required to separate
the carboxylic acid byproducts in oxidations involving peroxy
acids.
Oxidation by moist MMPP is not limited to sulfides.
Treatment of the cyclohexenes 4 afforded the epoxides 5
Solid reagents supported on silica gel and alumina have
found wide use in numerous synthetic applications.10 The
present results indicate that in some, but not all, of these
cases the adsorbent can be eliminated. This both simplifies
the experimental procedure and indicates that the adsorbent
may not be involved mechanistically. The role of water,
which must be present in specific amounts that vary for each
reagent, is apparently to both facilitate diffusion and impart
requisite physical properties, especially dispersibility, to the
(Table 2). As expected, the trisubstituted analogue 4b
Table 2. Epoxidation of Cyclohexenes 4 with Moist MMPPa
1
1
yield, %b
solid reagent. In addition to affording a convenient
experimental procedure, unsupported heterogeneous reagents
can retain the selectivities, including stereoselectivities,
exhibited by supported reagents that complement those from
traditional solution-phase methods. Our studies in the
fascinating realm of surface-mediated reactivity continue.
alkene
MMPP, mmol
time, h
4
5
4a
4b
4c
1.0
0.5
1.0
7
5
24
5
2
49
93
98
41
a
Conducted at 25 °C by treating a solution of 1.0 mmol of alkene 4 in
mL of CH2Cl2 with the indicated amount of MMPP that had been
moistened with 100 µL of water/mmol. Determined by H NMR analysis
relative to diphenylmethane as an internal standard.
5
b
1
Acknowledgment. Generous financial support by the
National Science Foundation and the Petroleum Research
Fund, administered by the American Chemical Society, is
gratefully acknowledged.
underwent epoxidation more rapidly than the less highly
substituted cyclohexene (4a), but the rate decreased on going
to the tetrasubstituted analogue 4c, which underwent only
slow oxidation. By contrast, in aqueous ethanolic solution
OL990823X
(7) OXONE is a product of the Du Pont Company consisting of a 2:1:1
mixture of the active ingredient KOSO2OOH, along with KHSO4 and K2-
SO4, respectively.
(8) Ca(COCl)2: Hirano, M.; Yakabe, S.; Itoh, S.; Clark, J. H.; Morimotoa,
T. Synthesis 1997, 1161-1164. OXONE: Kropp, P. J.; Breton, G. W.;
Fields, J. D.; Tung, J. C.; Loomis, B. R. Submitted.
(
9) (a) Liu, K.-T.; Tong, Y.-C. J. Org. Chem. 1978, 43, 2717-2718. (b)
Gupta, D. N.; Hodge, P.; Davies, J. E. J. Chem. Soc., Perkins Trans. 1
1
981, 2970-2973. (c) Varma, R. S.; Saini, R. K.; Meshram, H. M.
Tetrahedron Lett. 1997, 38, 6525-6528.
the relative rates of oxidation followed the expected order:
(10) For reviews, see: (a) PreparatiVe Chemistry Using Supported
Reagents; Laszlo, P., Ed.; Academic: San Diego, 1987. (b) Solid Supports
and Catalysts in Organic Synthesis; Smith, K., Ed.; Ellis Horwood: New
York, 1992. (c) Clark, J. H. Catalysis of Organic Reactions by Supported
Inorganic Reagents; VCH: New York, 1994.
4c > 4b > 4a (Table 3). Thus for tetrasubstituted alkenes
under heterogeneous conditions, steric hindrance apparently
outweighs the favorable electronic effect of the substituents.
(11) Reactions of solid-supported reagents are usually described as
7
Moist Ca(OCl)
2
and OXONE, both of which also effect
requiring moist silica gel or alumina. The present results suggest that the
emphasis should be on the reagent as being moist.
oxidation of sulfides as supported reagents,8 displayed
904
Org. Lett., Vol. 1, No. 6, 1999