Reaction of Stable Sulfenic and Selenenic Acids Containing a Bowl-type Steric Protection Group with a Phosphine. Elucidation of the Mechanism of Reduction of Sulfenic and Selenenic Acids

Article abstract of DOI:10.1246/cl.2003.1080

The mechanism of the reduction of the stable sulfenic acid 1 and selenenic acid 2 containing a bowl-type steric protection group by triphenylphosphine was elucidated by tracer studies using H₂¹⁸O. It was found that the initial step of the reaction involves the attack of the phosphine on the sulfur or selenium atom of 1 and 2, respectively, in contrast with the reduction of hydroperoxides by a phosphine, where the initial attack occurs on the hydroxylic oxygen.

Full text of DOI:10.1246/cl.2003.1080

1080
Chemistry Letters Vol.32, No.11 (2003)
Reaction of Stable Sulfenic and Selenenic Acids Containing a Bowl-type Steric Protection
Group with a Phosphine. Elucidation of the Mechanism of Reduction of Sulfenic
and Selenenic Acids
Kei Goto,Ã Keiichi Shimada, Michiko Nagahama, Renji Okazaki,# and Takayuki KawashimaÃ
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
(Received September4, 2003; CL-030815)
The mechanism of the reduction of the stable sulfenic acid 1
and selenenic acid 2 containing a bowl-type steric protection
group by triphenylphosphine was elucidated by tracer studies us-
ing H218O. It was found that the initial step of the reaction in-
Scheme 1.
volves the attack of the phosphine on the sulfurorselenium atom
of 1 and 2, respectively, in contrast with the reduction of hydro-
of hydroperoxides with trivalent phosphorus reagents.6b One
peroxides by a phosphine, where the initial attack occurs on the
hydroxylic oxygen.
to that of hydroperoxides.
Two possible mechanisms were considered for the reduction
mechanism involves the initial attack of the phosphorus on the
hydroxylic oxygen atom to form the intermediate I, and the other
involves the alkoxyphosphonium hydroxide intermediate II. In
1960, Denny et al. provided evidence ruling out the alkoxyphos-
Sulfenic acids (RSOH) and selenenic acids (RSeOH) are
well recognized as important intermediates in organic and bio-
phonium intermediate II and supporting the involvement of in-
chemical reactions of sulfur and selenium compounds.1,2 They
can be regarded as sulfur and selenium analogs of hydroperox-
ides (ROOH) and their properties as oxidizing agents have been
attracting wider attention in view of their critical role in redox
regulation in some enzymatic reactions.3,4 Undernon-enzymatic
conditions, however, little information has been obtained about
oxidation reactions by sulfenic acids or selenenic acids because
of their notorious instability; they readily undergo self-conden-
sation to the corresponding thiosulfinates1 orselenoseleni-
nates,2,5 respectively. While the mechanism of the reduction of
hydroperoxides by trivalent phosphorus compounds has been
elucidated in detail,6 no such mechanistic study has been per-
formed on the reaction of sulfenic and selenenic acids. We pre-
viously reported the synthesis of the stable sulfenic acid 17 and
selenenic acid 28 containing a novel bowl-type steric protection
group (denoted as Bmt).9 In this communication, we present the
mechanistic elucidation of the reduction of sulfenic and selenen-
ic acids by a phosphine by taking advantage of these stable sul-
fenic and selenenic acids.
termediate I by a tracer study using H218O.6b They showed that
cumyl hydroperoxide was reduced with phosphine 3 in ethanol–
H218O to give cumyl alcohol and phosphine oxide 5, neitherof
which contained oxygen-18. This is inconsistent with the forma-
tion of intermediate II, which should be accompanied by equili-
brium between the hydroxide ion and H218O.
Since it has been found that sulfenic acid 1 and selenenic
acid 2 oxidize phosphine 3 to phosphine oxide 5 as do hydroper-
oxides, it is intriguing whether the reaction mechanism is the
same as that of hydroperoxides or not. Tracer experiments sim-
ilar to those of Denny et al. were carried out with 1 and 2. Sul-
fenic acid 1 was allowed to react with phosphine 3 in a mixture
of THF–H218O (18O content: 19.2%), and the electron impact
mass spectrometry analysis of the resulting phosphine oxide 5
indicated that it contains oxygen-18 in 14.7 atom%, which corre-
sponds to the exchange rate of 77% (Scheme 2). Under the same
conditions, the reaction of t-butyl hydroperoxide with phosphine
3 gave phosphine oxide 5 containing no oxygen-18, which is in
agreement with the results of Denny et al. By control experi-
ments, it was confirmed that no exchange of oxygen between
phosphine oxide 5 and H218O occurs in the presence of either
sulfenic acid 1 orthiol 4 (Scheme 3). The absence of exchange
of oxygen between 1 and H218O was also confirmed (Scheme 3).
Similar results were obtained in the reduction of selenenic
acid 2. The reaction of selenenic acid 2 with phosphine 3 in
THF–H218O (18O content: 19.2%) produced phosphine oxide 5
containing oxygen-18 in 16.7 atom%, which corresponds to the
exchange rate of 87% (Scheme 4). In the control experiments,
It has been suggested that trivalent phosphorus reagents re-
duce transiently-generated sulfenic acids.10 We previously
reported that the reaction of BmtSOH (1) with triphenylphos-
phine (3) produced BmtSH (4) and triphenylphosphine oxide
(5) almost quantitatively.7 There has been no report in the liter-
ature on the reaction of a selenenic acid with trivalent phospho-
rus reagents. Treatment of selenenic acid 2 with an equimolar
amount of phosphine 3 in THF at room temperature resulted in
the quantitative formation of selenol 6 and phosphine oxide 5,
which was confirmed by the 1H and 31P NMR spectra of the re-
action mixture (Scheme 1). These results demonstrate that sul-
fenic acids and selenenic acids have an oxidizing ability similar
Scheme 2.
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.11 (2003)
1081
This work was partly supported by Grants-in-Aid for the
21st Century COE Program for Frontiers in Fundamental Chem-
istry (T.K.) and for Scientific Research (Nos. 12042220,
14703066 (K.G.), and 15105001 (T.K.)) from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
We also thank Tosoh Finechem Corporation for the generous
gifts of alkyllithiums.
References and Notes
#
Present address: Department of Chemical and Biological
Sciences, Faculty of Science, Japan Women’s University,
2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681.
1
For leading references on the chemistry of sulfenic acids,
see: a) D. R. Hogg, in ‘‘The Chemistry of Sulfenic Acids
and TheirDerivatives,’’ ed. by S. Patai, John Wiley & Sons,
New York (1990), p 361. b) J. L. Kice, Adv. Phys. Org.
Chem., 17, 65 (1980).
Scheme 3.
Scheme 4.
2
For leading references on the chemistry of selenenic acids,
see: a) ‘‘The Chemistry of Organic Selenium and Tellurium
Compounds,’’ ed. by S. Patai and Z. Rappoport, John Wiley
& Sons, New York (1986, 1987), Vol. 1, 2. b) ‘‘Organosele-
nium Chemistry,’’ ed. by D. Liotta, John Wiley & Sons, New
York (1987).
For leading references on the biochemical reactions of sul-
fenic acids, see: a) W. S. Allison, Acc. Chem. Res., 9, 293
(1976). b) A. Claiborne, T. Conn Mallett, J. I. Yeh, J. Luba,
and D. Parsonage, Adv. Protein Chem., 58, 215 (2001).
For leading references on the biochemical reactions of sele-
nenic acids, see: a) H. E. Ganterand R. J. Kraus, in ‘‘Meth-
ods in Enzymology,’’ ed. by S. P. Colowick and N. O.
Kaplan, Academic Press, New York (1984), Vol. 107, p
no exchange of oxygen atom eitherbetween phosphine oxide 5
and H218O, orbetween 2 and H218O was observed (Scheme 3).
The incorporation of oxygen-18 in 5 at the high exchange
rates of 77 and 87% indicates that the reactions proceed via
the initial attack of the phosphorus atom of 3 on the sulfuratom
of 1 orthe selenium atom of 2 to give the intermediate IV (Route
(B) in Scheme 5), not on the hydroxylic oxygen to give the inter-
mediate III (Route (A)). Although the possibility that very small
portions of these reactions proceed via Route (A) cannot be ruled
out, undoubtedly Route (B) is predominant in contrast with the
reduction of hydroperoxides. The arylthio- or arylselenophos-
phonium intermediate IV is considered to yield the products
via the pentacoordinated species V. It may be noted that the nu-
cleophilic attack of a relatively bulky phosphine 3 occurs at the
sulfur and selenium atoms, even though they are incorporated in
the cavity of the Bmt group and less accessible than the hydrox-
ylic oxygen on steric grounds. It is likely that such high electro-
philic character of the sulfur and selenium atoms of sulfenic and
selenenic acids plays an important role in their function as oxi-
dizing agents in biological systems.
3
4
´
593. b) L. Flohe, in ‘‘Signal Transduction by Reactive
Oxygen and Nitrogen Species: Pathways and Chemical
Principles,’’ ed. by H. J. Forman, J. Fukuto, and M. Torres,
Kluwer Academic Publishers, Dordrecht (2003).
A. Ishii, S. Matsubayashi, T. Takahashi, and J. Nakayama, J.
Org. Chem., 64, 1084 (1999).
a) A. J. Kirby and S. G. Warren, ‘‘The Organic Chemistry of
Phosphorus,’’ Elsevier Pub. Co., Amsterdam (1967), p 72. b)
D. B. Denney, W. F. Goodyear, and B. Goldstein, J. Am.
Chem. Soc., 82, 1393 (1960). c) R. Hiatt, R. J. Smythe,
and C. McColeman, Can. J. Chem., 49, 1707 (1971). d) J.
I. Shulman, J. Org. Chem., 42, 3970 (1977).
5
6
In summary, the mechanism of the reduction of sulfenic and
selenenic acids by a phosphine was elucidated forthe first time
by taking advantage of stable compounds containing a bowl-type
steric protection group. Further investigations on the mechanism
of their reactions with other substrates are currently in progress.
7
8
9
K. Goto, M. Holler, and R. Okazaki, J. Am. Chem. Soc., 119,
1460 (1997).
K. Goto, M. Nagahama, T. Mizushima, K. Shimada, T.
Kawashima, and R. Okazaki, Org. Lett., 3, 3569 (2001).
Forotherexamples of application of the bowl-type mole-
cules, see: a) Microreview: K. Goto and R. Okazaki, Liebigs
Ann./Recl., 1997, 2393. b) T. Saiki, K. Goto, and R.
Okazaki, Angew. Chem., Int. Ed. Engl., 36, 2223 (1997). c)
K. Goto, Y. Hino, T. Kawashima, M. Kaminaga, E. Yano,
G. Yamamoto, N. Takagi, and S. Nagase, Tetrahedron Lett.,
41, 8479 (2000). d) K. Goto, Y. Hino, Y. Takahashi, T.
Kawashima, G. Yamamoto, N. Takagi, and S. Nagase,
Chem. Lett., 2001, 1204.
´
10 a) R. D. G. Cooperand F. L. Jose , J. Am. Chem. Soc., 92,
2575 (1970). b) L. D. Hatfield, J. Fisher, F. L. Jose, and R.
´
D. G. Cooper, Tetrahedron Lett., 1970, 4897.
Scheme 5.
Published on the web (Advance View) October27, 2003; DOI 10.1246/cl.2003.1080