The first example of a singlet oxygen induced double bond migration during sulfide photooxidation. Experimental evidence for sulfone formation via a hydroperoxy sulfonium ylide

Article abstract of DOI:10.1021/jo016219t

The first example of the formation of a sulfone concomitant with double bond migration aunng photooxidation of a sulfide is reported. Evidence is presented which demonstrates that the double bond migration is not a result of a prior acid-catalyzed rearrangement of an unrearranged sulfone precursor. This unusual observation is used to argue that the sulfone is formed via rearrangement of a hydroperoxy sulfonium ylide intermediate.

Full text of DOI:10.1021/jo016219t

1036
J . Org. Chem. 2002, 67, 1036-1037
Sch em e 1. Su lfon e F or m a tion via th e
Th e F ir st Exa m p le of a Sin glet Oxygen
Hyd r op er oxy Su lfon iu m Ylid e
In d u ced Dou ble Bon d Migr a tion d u r in g
Su lfid e P h otooxid a tion . Exp er im en ta l
Evid en ce for Su lfon e F or m a tion via a
Hyd r op er oxy Su lfon iu m Ylid e
Edward L. Clennan* and David Aebisher
Sch em e 2. P r od u cts fr om P h otooxid a tion of 2
Department of Chemistry, University of Wyoming,
Laramie, Wyoming 82071
Clennane@uwyo.edu
Received October 19, 2001
Abstr a ct: The first example of the formation of a sulfone
concomitant with double bond migration during photooxi-
dation of a sulfide is reported. Evidence is presented which
demonstrates that the double bond migration is not a result
of a prior acid-catalyzed rearrangement of an unrearranged
sulfone precursor. This unusual observation is used to argue
that the sulfone is formed via rearrangement of a hydro-
peroxy sulfonium ylide intermediate.
Sch em e 3
The reactions of singlet oxygen with organic sulfides
have been vigorously studied1-5 since the seminal report
of Schenck and Krauch in 1962.6 The recognition of the
ability of sulfides to act as antioxidants and of their
pivotal role in biological systems has been the driving
force behind the intense interest in these reactions.
Despite the flurry of activity in this area, new fascinating
aspects of these reactions are still being reported. For
example, in 1996 Ishiguro, Hayashi, and Sawaki7suggested
that the small amount of sulfone formation in these
reactions was in part derived from rearrangement of a
hydroperoxy sulfonium ylide, 1 (Scheme 1). Their evi-
dence consisted of the observations that the two oxygen
atoms were derived from the same oxygen molecule and
that isotopic exchange at the R-position accompanied
sulfone formation.
We report here the first example of a double bond
migration during photooxidation at sulfur.8 We also argue
that this reaction provides independent verification of the
role of the hydroperoxy sulfonium ylide, 1, in sulfone
formation.
Photooxidation of a 0.05 M C6D6 oxygen saturated
solution of ethyl γ-phenylthiocrotonate, 2, containing 2.5
× 10-4 M tetraphenylporphyrin to 80% conversion re-
sulted in formation of the products shown in Scheme 2.
Nearly identical results were obtained in CDCl3 with the
exception of the formation of a trace amount of 3SO2 and
formation of 5% of an unknown.
Et3N to provide a thermodynamic mixture of sulfides as
depicted in Scheme 3. These were then treated with 2
equiv of MCPBA to generate the corresponding sulfones
in the same ratio as the sulfide precursors. The structures
of the sulfides and sulfones could be unambiguously as-
signed by examination of the chemical shifts and coupling
constants of the diagnostic HR, Hâ, and Hγ protons.9
The possibility that sulfone 2SO2 could have served
as the precursor of the unanticipated double bond mi-
grated sulfones 4SO2 and 5SO2 was ruled out in two
different experiments. (1) Treatment of the 2SO2:3SO2:
4SO2:5SO2 mixture shown in Scheme 3 with Et3N in
refluxing benzene resulted in the quantitative formation
of 89% of 2SO2 and 11% of 3SO2. The absence of the
double bond migrated isomers 4SO2 and 5SO2 demon-
strate that they are kinetic and not thermodynamic
products in the photooxidation of 2. (2) Cophotooxidation
of methyl allyl sulfide and 2SO2 under the identical
conditions utilized for the reaction of 2 resulted in
Sulfoxide 2SO and sulfone 2SO2 were identical to the
products formed when 2 was treated with 1 and 2 equiv
of MCPBA, respectively. To provide unambiguous as-
signments for the remaining sulfones, 2 was treated with
(8) A double bond migration occurs during the singlet oxygen ene
reaction but in that case the double bond is the seat of reactivity.
(9) 1H NMR (benzene-d6) δ Compound 2 δ 5.75(HR, dt, J ) 16, 1
Hz), ≈ 6.9(Hâ, buried in the aromatic region), 3.00(Hγ dd, J ) 7, 1
Hz); Compound 3 δ 5.60(HR, dt, J ) 11, 1 Hz), 5.87(Hâ, dt, J ) 11, 8
Hz), 4.11(Hγ dd, J ) 8, 1 Hz); Compound 4 δ 2.70(HR, d, J ) 6.5 Hz),
5.96(Hâ, dt, J ) 16, 7 Hz), 6.04(Hγ d, J ) 15 Hz); Compound 5 δ 3.20-
(HR, dd, J ) 7, 2 Hz), 5.95(Hâ, dt, J ) 9, 7 Hz), 6.16(Hγ dt, J ) 9, 2
Hz); Compound 2SO2 δ 5.54(HR, bd, J ) 16 Hz), (Hâ, buried in aromatic
region), 3.20(Hγ dd, J ) 8, 1 Hz); Compound 3SO2 δ 5.61(HR, dt, J )
11, 1 Hz), 5.91(Hâ, dt, J ) 11, 8 Hz), 4.43(Hγ dd, J ) 8, 1 Hz);
Compound 4SO2 δ 2.46(HR, dd, J ) 7, 2 Hz), (Hâ, buried in aromatic
region), 6.00(Hγ dt, J ) 15, 2 Hz); Compound 5SO2 δ 3.67(HR, dd, J )
7, 2 Hz), 6.11(Hâ, dt, J ) 11, 7 Hz), 5.87(Hγ dt, J ) 11, 2 Hz).)
(1) Clennan, E. L. Tetrahedron 2000, 56, 9151-9179.
(2) J ensen, F.; Greer, A.; Clennan, E. L. J . Am. Chem. Soc. 1998,
120, 4439-4449.
(3) Bonesi, S. M.; Albini, A. J . Org. Chem. 2000, 65, 4532-4536.
(4) Bonesi, S. M.; Torriani, R.; Mella, M.; Albini, A. Eur. J . Org.
Chem. 1999, 1723-1728.
(5) Bonesi, S. M.; Mella, M.; d’Alessandro, N.; Aloisi, G. G.; Vanossi,
M.; Albini, A. J . Org. Chem. 1998, 63, 9946-9955.
(6) Schenck, G. O.; Krauch, C. H. Angew. Chem. 1962, 74, 510.
(7) Ishiguro, K.; Hayashi, M.; Sawaki, Y. J . Am. Chem. Soc. 1996,
118, 7265-7271.
10.1021/jo016219t CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/16/2002

Notes
J . Org. Chem., Vol. 67, No. 3, 2002 1037
corresponding to the residual protons of CDCl3 (7.37 ppm) or
C6D6 (7.16 ppm) were used as the internal reference. An HP-5
(30 m × 0.25 mm × 0.25 µm (length × inside diameter × film
thickness)) capillary column and a 5% diphenyl-95% dimethyl
polysiloxane (30 m × 0.32 mm × 1.0 µm (length × inside
diameter × film thickness)) fused silica column were used to
monitor the formation of a key intermediate (ethyl γ-bromo-
trans-crotonate)15-17 in the synthesis of 2. Radial chromatogra-
phy to purify 2 was carried out using silica gel 60 PF254 from
EM Science.
Sch em e 4
Chloroform-d (110 g; Cambridge Isotope Laboratories) was
extracted with 40 mL of saturated aqueous sodium bicarbonate,
dried with magnesium sulfate, and stored over 4A molecular
sieves prior to use. Benzene-d6 was obtained from Cambridge
Isotope Laboratories and used without further purification.
Triethylamine was obtained from Eastman Chemical and dis-
tilled prior to use. Thiophenol was obtained from Acros Chemical
and used without further purification. Compounds 2,15-17 2SO,18
2SO2,19 3,20 4,16,17 4SO2,21 5,16,17 and ethyl 4-oxo-2-butenoate22
are all known compounds and provide spectral data consistent
with their structures. Ethyl trans-crotonate was obtained from
Aldrich Chemical and distilled prior to use.
Sch em e 5
P h otooxid a tion P r oced u r e. Photooxidation reaction mix-
tures 0.05 M in 2 and 2.5 × 10-4 M in tetraphenylporphyrin
(TPP) were prepared in either CDCl3 or C6D6 in 5 mL volumetric
flasks. The mixtures in CDCl3 were treated with 0.25 g of
Na2CO3 and allowed to stir for 10 min in the dark to remove
residual acid. The solutions were then filtered and divided into
1 mL portions for irradiation in 100 mL test tubes. The samples
were presaturated with oxygen for 2 min and then irradiated
under a constant stream of oxygen with a 600 W tungsten lamp
at 23 °C through 1 cm of a 12 M NaNO2 filter solution. After
the photooxidations, the samples were kept in the dark and
analyzed by 1H NMR as quickly as possible (5-10 min after
photooxidation). The product ratios represent the averages of
from three to four independently photooxidized samples.
Isom er iza tion of 2. The isomerization procedure used was
that of O’Connor and Lyness.23 A mixture of 0.1 g of 2 and 5 mL
of triethylamine was refluxed for 1 to 3 h. Triethylamine was
then removed by rotary evaporation to yield a dark liquid
consisting of 38% 2, 3% 3, 28% 4, and 31% 5. This product
composition was independent of reflux time between 1 and 3 h.
quantitative recovery of 2SO2 without formation of the
double bond migrated isomers.10
The formation of the albeit minor but nevertheless
mechanistically diagnostic double bond migrated sulfones
can most easily be rationalized as shown in Scheme 4.
The persulfoxide I formed from the addition of singlet
oxygen to 2 can form two hydroperoxy sulfonium ylides
A and B by abstraction of diastereomeric protons from
the γ-carbon in the persulfoxide. The hydroperoxy sul-
fonium ylides can subsequently rearrange by a 1,2-
hydroxy shift to give sulfone enolates C and D which can
be protonated at the ends of the allyl anion to give 2SO2
and a double bond migrated product. This mechanism
also provides a very satisfying rationale for the absence
of 3SO2 since its formation would require prohibitively
difficult isomerization around either the double bond in
the persulfoxide, I, or the allyl anion in A or B.11
The transition state for the migration of the hydroxy
group from oxygen to sulfur in the hydroperoxy sulfonium
ylide derived from dimethyl sulfide has been located and
optimized at the MP2/6-31G(d) level2 (Scheme 5). The
ylide carbon is rotated and the p-orbital is directed
toward the migrating OH group in order to provide
conjugative stabilization to the transition state. An
analysis of the rotational profile about the ylide carbon
suggested that this overlap provides approximately 10
kcal/mol stabilization of the transition state.11 Conse-
quently, the delocalized negative charge in the novel
hydroperoxy sulfonium ylides A and B (Scheme 4) might
be responsible in part for the very small yields of sulfones
produced in the reaction of 2 and other allylic and
benzylic sulfides.12
Ack n ow led gm en t. The generous support of the
National Science Foundation and the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, is gratefully acknowledged.
J O016219T
(10) The methyl allyl sulfide reacted to produce 85% of the corre-
sponding sulfoxide, 6% of the corresponding sulfone, and 9% of the
Pummerer S-C bond cleavage products.
(11) The barrier for rotation around a thiophenyl substituted allyl
anion has been reported to be 19 kcal/mol. Biellmann, J . F.; Ducep, J .
B. Tetrahedron 1971, 27, 5861-5872.
(12) Toutchkine, A.; Aebisher, D.; Clennan, E. L. J . Am. Chem. Soc.
2001, 123, 4966-4973.
(13) Toutchkine, A.; Clennan, E. L. J . Org. Chem. 1999, 64, 5620-
5625.
(14) Toutchkine, A.; Clennan, E. L. J . Am. Chem. Soc. 2000, 122,
1834-1835.
(15) Fleming, I.; Goldhill, J .; Paterson, I. Tetrahedron Lett. 1979,
3205-3208.
(16) Brownbridge, P.; Hunt, P. G.; Warren, S. Tetrahedron Lett.
1983, 24, 3391-3394.
These results highlight the multifaceted behavior of
the hydroperoxy sulfonium ylide (1 in Scheme 1 and A
and B in Scheme 4). These versatile intermediates have
now been implicated in reductive conversion to sulfides,13
in rearrangement to sulfones, and in the Pummerer
rearrangement to R-hydroperoxy sulfides and ultimately
S-C bond cleavage products.14
(17) Brownbridge, P.; Durman, J .; Hunt, P. G.; Warren, S. J . Chem.
Soc., Perkin Trans. 1 1986, 1947-1958.
(18) Lansbury, P. T.; Erwin, R. W.; J effrey, D. A. J . Am. Chem. Soc.
1980, 102, 1602-1608.
(19) Annunziata, R.; Barbarella, G. Org. Magn. Reson. 1984, 22,
250-254.
(20) Rho, Y. S.; Kang, H. S.; Sin, H. S. Yakhak Hoechi 1993, 37,
555-560.
(21) Davies, H. M. L.; Clark, T. J .; Smith, H. D. J . Org. Chem. 1991,
56, 3817-3824.
Exp er im en ta l Section
(22) Naef, F.; Decorzant, R.; Thommen, W. Helv. Chim. Acta 1982,
65, 2212-2223.
Proton NMR spectra of CDCl3 or C6D6 solutions of substrates
and reaction mixtures were recorded at 400.13 MHz. The peaks
(23) O’Connor, D. E.; Lyness, W. I. J . Am. Chem. Soc. 1964, 86,
3840-3846.