Photoinduced highly selective thiophosphination of alkynes using a (PhS)2/(Ph2P)2 binary system

Article abstract of DOI:10.1016/j.tetlet.2008.04.068

Development of highly selective method for simultaneous introduction of different heteroatom functions into carbon-carbon unsaturated bonds is of special interest. When a mixture of tetraphenyldiphosphine (Ph₂P)₂ and diphenyl disulfide (PhS)₂, and phenylacetylene in CDCl₃ was irradiated with a xenon lamp through Pyrex at ambient temperature, a highly regioselective addition of phosphino and thio groups into carbon-carbon triple bond took place simultaneously to give the corresponding thiophosphination product in high yield.

Full text of DOI:10.1016/j.tetlet.2008.04.068

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Tetrahedron Letters 49 (2008) 4043–4046
Photoinduced highly selective thiophosphination of alkynes
using a (PhS)2/(Ph2P)2 binary system
Takamune Shirai, Shin-ichi Kawaguchi, Akihiro Nomoto *, Akiya Ogawa *
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
Received 2 March 2008; revised 8 April 2008; accepted 11 April 2008
Available online 14 April 2008
Abstract
Development of highly selective method for simultaneous introduction of different heteroatom functions into carbon–carbon unsat-
urated bonds is of special interest. When a mixture of tetraphenyldiphosphine (Ph2P)2, diphenyl disulfide (PhS)2, and phenylacetylene in
CDCl3 was irradiated with a xenon lamp through Pyrex at ambient temperature, a highly regioselective addition of phosphino and thio
groups into carbon–carbon triple bond took place simultaneously to give the corresponding thiophosphination product in high yield.
Ó 2008 Elsevier Ltd. All rights reserved.
Radical addition of heteroatom compounds to carbon–
carbon unsaturated bonds based on the photoinduced
homolytic cleavage of heteroatom–heteroatom linkage is
Br
one of the most useful and highly atom-economical meth-
h
ν
(> 350 nm)
SPh
ods for the selective introduction of heteroatom functions
into organic molecules.1 In particular, the development of
a highly selective method for simultaneous introduction
of different heteroatom functions into carbon–carbon
unsaturated bonds is of special interest.2,3
(Ph2P)2
(PhS)2
+
Br
+
CDCl3, r.t., 2 h
Ph2P
1
4a
78%
3a
0.5 mmol
2
1 equiv
1 equiv
ð1Þ
Br
Herein we report a highly regioselective photoinduced
thiophosphination of alkynes using a novel diphosphine-
disulfide binary system (Eq. 1).4,5 It has become apparent
for this methodology that the present thiophosphination
proceeds smoothly at room temperature using commer-
cially available (Ph2P)2 and (PhS)2 as the starting reagents
with excellent E-selectivity and can be applied to internal
alkynes.
When a mixture of tetraphenyldiphosphine (1 mmol),
diphenyl disulfide (1 mmol), and 1-bromo-4-ethynyl-ben-
zene (0.5 mmol) in CDCl3 (0.6 mL) was irradiated with a
xenon lamp through Pyrex for 2 h at ambient temperature,
a novel highly regioselective thiophosphination took place
O2
SPh
Ph2P
O
5a
62%
to give the corresponding thiophosphination product (4a).
The present thiophosphination proceeded smoothly with-
out a decrease in the yield of 4a, even when stoichiometric
(or slightly excess) amounts of (Ph2P)2 (0.6 mmol) and
(PhS)2 (0.6 mmol) were employed. A consequent air-oxida-
tion of 4a afforded the corresponding oxide (5a)
in high isolated yield.6,7 Interestingly, in this thiophos-
phination using a (PhS)2/(Ph2P)2 binary system, neither
bisphosphination product nor bisthiolation product was
*
Corresponding authors.
E-mail address: ogawa@chem.osakafu-u.ac.jp (A. Ogawa).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.068

4044
T. Shirai et al. / Tetrahedron Letters 49 (2008) 4043–4046
formed. When the reaction was conducted in the dark,
thiophosphination did not proceed.
0.2
Compound 5a was recrystallized from EtOH to obtain a
single crystal suitable for X-ray analysis. The regio- and
stereochemistries of the major product ((E)-5a) were fully
determined by the X-ray crystallographic analysis (Fig. 1).7
A possible reaction pathway for the thiophosphination
is as follows (Scheme 1). Figure 2 indicates UV–visible
spectra of (Ph2P)2, (PhS)2, and thiophoshine (6) (Fig. 2).
(PhS)2
Abs
(Ph2PSPh)
0.1
0
(Ph2P)2
*
The absorption based on the n-r transition of (Ph2P)2,
(PhS)2, and thiophoshine (6) reaches 330 nm, 375 nm,
and 370 nm, respectively.8 Therefore, irradiation with the
light of wavelength over 350 nm induces preferential cleav-
age of S–S single bond, generating PhSÅ, which adds to
alkynes to form vinylic radical (7) (Scheme 1). PhSÅ also
attacks (Ph2P)2 to give thiophosphine (6)9 and Ph2PÅ, the
former of which captures the vinylic radical (7) to afford
the thiophosphinated product (4) regioselectively.10
250
300
350
400
nm
Fig. 2. UV–visible spectra of (Ph2P)2 (- - -), (PhS)2 (– ꢀ –) and Ph2PSPh (—).
Table 1
Photoinduced thiophosphination of alkynes
h
ν (> 350 nm)
Similar conditions can be employed with several acetyl-
enes (3b–g) (Table 1). In the case of aromatic acetylenes
+
+
(PhS)
R
(Ph P)
2
2
2
CDCl , r.t.
3
3
1
2
1 equiv
1 equiv
0.5 mmol
R
SPh
R
SPh
O(S)
O or S
2
8
Ph P
2
Ph P
2
r.t.
4
5
Entry Alkyne
Time (h)
1
Yield (%) (E/Z)
4a
5b
1
91 [91/9]
90 [91/9]
61
60
MeO
(3b)
n
2
1
2
(3c)
C H
5
11
3
87 [90/10] 73
(3d)
(3e)
(3f)
4c
5c
27
20
77 [94/6]
61 [93/7]
57
41
n
C H
6
13
Ph
Fig. 1. Molecular structure of (E)-5a by X-ray crystallographic studies.
Space group: C2/c (#15), Z = 8, R = 0.0665, Rw = 0.0729, GOF = 1.075,
˚
6c
48
80 [75/25] 67 [71/29]d
Selected bond lengths (A) and angles (°): C(1)–C(2) = 1.331(7), P–C(1) =
(3g)
1.796(4), S–C(2) = 1.736(4), C(1)–C(3) = 1.480(6), P–C(1)–C(2) =
121.7(3), S–C(2)–C(1) = 122.4(3).
a
1H NMR yield.
b
c
Isolated yield of E-isomer.
Sulfurization with S8 instead of air-oxidation.
Obtained as a mixture of E- and Z-isomers.
d
hν>350 nm
R
R
(PhS)2
PhS
SPh
(7)
(entries
1 and 2), the thiophosphination proceeded
(Ph2P)2 - Ph2P
smoothly and E isomers (5b and 5c) were obtained as the
major product. The thiophosphination of enyne (3d) pro-
ceeded on the triple bond selectively (entry 3). Aliphatic
alkynes also underwent regioselective thiophosphination,
although a prolonged irradiation was required (entries 4
and 5).11 Noteworthy is that the thiophosphination of 1-
phenyl-1-pentyne (3g) as an internal alkyne also proceeded
regioselectively in good yields (entry 6).12
Ph2PSPh
(6)
- PhS
R
SPh
Ph2P
(4)
As an extention of the current (Ph2P)2–(PhS)2 binary
system, the thiophosphination reaction of an enyne via
Scheme 1. A possible pathway for thiophosphination.

T. Shirai et al. / Tetrahedron Letters 49 (2008) 4043–4046
4045
EtO2C CO2Et
+
EtO2C CO2Et
h
ν
(> 350 nm)
S8
(Ph2P)2
(PhS)2
+
CDCl3, r.t., 35 h
Ph2P
SPh
S
3h
1
2
5h, 40%
S8
EtO2C CO2Et
EtO2C CO2Et
SPh
Ph2PSPh
5-exo-trig
PhS
SPh
Scheme 2. Photoinduced thiophosphination of enyne.
5-exo radical cyclization13 was demonstrated (Scheme 2).
The photoirradiated reaction of diethyl allylpropargylmal-
onate (3h) with (Ph2P)2 and (PhS)2 successfully afforded the
corresponding five-membered cyclic product (5h) bearing
phenylthio and diphenylphosphino groups at both the
terminal positions regioselectively.14,15
In conclusion, we have developed a new method for the
simultaneous introduction of phosphino and thio groups
into carbon–carbon triple bonds with excellent regio- and
stereoselectivities by using a (Ph2P)2/(PhS)2 binary system
via photoirradiation under mild reaction conditions. We
are currently investigating its detailed mechanism and its
further application to other substrates.
2. (a) Toru, T.; Seko, T.; Maekawa, E.; Ueno, Y. J. Chem. Soc., Perkin
Trans. 1 1989, 1927; (b) Back, T. G.; Brunner, K.; Krishna, M. V.;
Lai, E. K. Y.; Muralidharan, K. R. In Heteroatom Chemistry; Block,
E., Ed.; VCH: New York, 1990. Chapter 4; (c) Back, T. G.
Phosphorous, Sulfur Silicon Relat. Elem. 1992, 67, 203; (d) Ogawa,
A.; Hirao, T. Rev. Heteroat. Chem. 1998, 18, 1; (e) Ogawa, A.;
Tanaka, H.; Yokoyama, H.; Obayashi, R.; Yokoyama, K.; Sonoda,
N. J. Org. Chem. 1992, 57, 111; (f) Ogawa, A.; Obayashi, R.; Ine, H.;
Tsuboi, Y.; Sonoda, N.; Hirao, T. J. Org. Chem. 1998, 63, 881; (g)
Ogawa, A.; Obayashi, R.; Sonoda, N.; Hirao, T. Tetrahedron Lett.
1998, 39, 1577; (h) Ogawa, A.; Obayashi, R.; Doi, M.; Sonoda, N.;
Hirao, T. J. Org. Chem. 1998, 63, 4277; (i) Ogawa, A.; Ogawa, I.;
Obayashi, R.; Umezu, K.; Doi, M.; Hirao, T. J. Org. Chem. 1999, 64,
86; (j) Tsuchii, K.; Doi, M.; Ogawa, I.; Einaga, Y.; Ogawa, A. Bull.
Chem. Soc. Jpn. 2005, 78, 1534; (k) Tsuchii, K.; Tsuboi, Y.;
Kawaguchi, S.; Takahashi, J.; Sonoda, N.; Nomoto, A.; Ogawa, A.
J. Org. Chem. 2007, 72, 415; (l) Mitamura, T.; Tsuboi, Y.; Iwata, K.;
Tsuchii, K.; Nomoto, A.; Sonoda, M.; Ogawa, A. Tetrahedron Lett.
2007, 48, 5953.
Acknowledgments
3. For examples of transition-metal-catalyzed addition: (a) Ishiyama, T.;
Nishijima, K.; Miyaura, N.; Suzuki, A. J. Am. Chem. Soc. 1993, 115,
7219; (b) Han, L.-B.; Choi, N.; Tanaka, M. J. Am. Chem. Soc. 1996,
118, 7000; (c) Han, L.-B.; Tanaka, M. J. Am. Chem. Soc. 1998, 120,
8249; (d) Han, L.-B.; Tanaka, M. Chem. Lett. 1999, 863; (e) Arisawa,
M.; Kazuki, Y.; Yamaguchi, M. J. Org. Chem. 2003, 68, 8964.
4. During the contribution of this Letter in this journal, thiophosphin-
ation of terminal alkynes with thiophosphines using radical initiator
has been reported: Wada, T.; Kondoh, A.; Yorimitsu, H.; Oshima, K.
Org. Lett. 2008, 10, 1155.
This work is supported by Grant-in-Aid for Scientific
Research on Priority Areas (Area 444, No. 19020061)
and Scientific Research (B, 19350095), from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan. Thanks are also due to the Analytical Center, Fac-
ulty of Engineering, Osaka University and the Graduate
School of Materials Science, Nara Institute of Science
and Technology for the use of their facilities.
5. Our preliminary results of this photoinduced thiophosphination and
relating works were presented at the 87th Annual Meeting of
Chemical Society of Japan (March 26, 2007, Suita, Osaka, Japan)
and the 34th Symposium on Main Group Element Chemistry
(December 15, 2007, Osaka, Japan).
References and notes
1. (a) Ogawa, A.. In Main Group Metals in Organic Synthesis;
Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim, 2004;
Vol. 2, p 813; Bisthiolation of alkynes: (b) Heiba, E. I.; Dessau, R. M.
J. Org. Chem. 1967, 32, 3837; Bisselenation of alkynes: (c) Back, T.
G.; Krishna, M. V. J. Org. Chem. 1988, 53, 2533; (d) Ogawa, A.;
Yokoyama, H.; Yokoyama, K.; Masawaki, T.; Kambe, N.; Sonoda,
N. J. Org. Chem. 1991, 56, 5721; Bistellulation of alkynes: (e) Ogawa,
A.; Yokoyama, K.; Yokoyama, H.; Obayashi, R.; Kambe, N.;
Sonoda, N. J. Chem. Soc., Chem. Commum. 1991, 1748; (f) Ogawa,
A.; Yokoyama, K.; Obayashi, R.; Han, L.-B.; Kambe, N.; Sonoda, N.
Tetrahedron 1993, 49, 1177; Bisphosphination of alkynes: (g)
Tzschach, V. A.; Baensch, S. J. Prakt. Chem. 1971, 313, 254; (h)
Sato, A.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2005, 44,
1694; (i) Kawaguchi, S.; Nagata, S.; Shirai, T.; Tsuchii, K.; Nomoto,
A.; Ogawa, A. Tetrahedron Lett. 2006, 47, 3919; (j) Dodds, D. L.;
Haddow, M. F.; Orpen, A. G.; Pringle, P. G.; Woodward, G.
Organometallics 2006, 25, 5937.
6. The isolation of 4a was difficult, due to the sensitivity of 4a toward
air-oxidation.
7. Compound (E)-5a: 1H NMR (500 MHz, CDCl3) d 7.05 (d, J = 7.3 Hz,
2H), 7.27–7.34 (m, 5H), 7.39–7.45 (m, 6 H), 7.50–7.53 (m, 2H), 7.56
(d, JH–P = 16.9 Hz, 1H), 7.64–7.68 (m, 4 H); 13C NMR (125 MHz,
CDCl3) d 122.42 (d, J = 1.9 Hz), 128.02 (d, J = 4.7, 1.9 Hz), 128.44
(dd, JC–P = 12.7, J = 1.9 Hz), 129.35 (d, J = 1.9 Hz), 129.83 (d,
JC–P = 96.9 Hz), 130.45 (d, J = 1.9 Hz), 131.09 (d, JC–P = 104.6 Hz),
131.26 (dd, J = 5.7, 3.8 Hz), 131.81 (d, J = 6.7 Hz), 132.04, 132.08 (d,
JC–P = 10.5 Hz), 133.63, 134.01 (d, JC–P = 8.6 Hz), 146.67 (dd, JC–P
=
14.4, J = 5.7 Hz); 31P NMR (200 MHz, CDCl3) d 26.66; HRMS
calcd for C26H20BrOPS: 490.0156, found: 490.0156. Anal. Calcd
for C26H20BrOPS: C, 63.55; H, 4.10. Found: C, 63.56; H, 4.10.
8. The UV spectra of diphenyl disulfide and tetraphenyl diphosphine are as
follows: (PhS)2: kmax = 250 nm, emax = 500; Schmidt, U.; Miiller, A.;
Markau, K. Chem. Ber. 1964, 97, 405; (Ph2P)2: kmax = 260 nm,

4046
T. Shirai et al. / Tetrahedron Letters 49 (2008) 4043–4046
max = 40; Troy, D.; Turpin, R.; Voigt, D. Bull. Soc. Chim. Fr. 1979,
133.89, 138.60 (d, JC–P = 9.5 Hz), 157.69 (d, JC–P = 13.4 Hz); 31P
e
241.
NMR (200 MHz, CDCl3) d 40.23; HRMS calcd for C29H27PS2:
470.1292, found: 470.1299.
13. Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical
Reaction; VCH: Weinheim, 1996.
9. The formation of thiophsophine (6) (d 33.0) was confirmed by 31P
NMR spectrum.
10. In this thiophosphination, recombination of heteroatom-centered
radicals such as PhSÅ and Ph2PÅ to form (PhS)2, (Ph2P)2, and/or
PhSPPh2 is conceivably a very fast process. Accordingly, the present
thiophosphination of alkynes requires continuous photoirradiation
during the reaction.
11. In the cases of aliphatic acetylene, prolonged reaction time was
required. This is because a-aryl-substituted vinylic radicals are
assumed to be p-radicals and more stable than alkyl-substituted
vinylic r-radicals. See: Singer, L. A.; Chen, J. Tetrahedron Lett. 1969,
10, 4849.
12. Compound (E)-5g: 1H NMR (500 MHz, CDCl3) d 0.35 (t, J = 7.3 Hz,
3H), 1.32–1.40 (m, 2H), 2.51 (t, J = 7.3 Hz, 2H), 6.99–7.06 (m, 5 H),
7.23–7.36 (m, 11 H), 7.78–7.82 (m, 4 H); 13C NMR (125 MHz,
CDCl3) d 13.47, 21.35, 35.77 (d, JC–P = 7.6 Hz), 127.00, 127.79,
127.85 (d, JC–P = 12.4 Hz), 128.12, 128.81, 129.88, 130.80, 131.92 (d,
J = 8.6 Hz), 132.25 (d, JC–P = 75.8 Hz), 132.89 (d, J = 110.3 Hz),
14. Compound 5h: 1H NMR (500 MHz, CDCl3) d 1.09–1.13 (m, 6 H), 1.65
(dd, J = 12.3, 9.6 Hz, 1H), 2.36–2.40 (m, 1 H), 2.55 (dt, J = 14.6,
9.6 Hz, 1H), 1.65 (dt, J = 13.3, 3.6 Hz, 1H), 2.84 (dt, J = 17.8, 2.3 Hz,
1H), 3.01 (d, J = 17.9 Hz, 1 H), 3.16–3.23 (m, 1 H), 4.03–4.08 (m,
4H), 5.98 (s, 1 H), 7.18–7.20 (m, 2 H), 7.33–7.41 (m, 8 H), 7.73–7.82
(m, 5 H); 13C NMR (125 MHz, CDCl3) d 13.90, 13.95, 37.22 (d,
JC–P = 54.6 Hz), 38.24, 40.55, 58.63, 59.35, 61.54, 115.21, 126.24,
128.48, 128.93, 130.81 (d, JC–P = 10.5 Hz), 131.22 (d, JC–P = 9.5 Hz),
131.48, 132.21 (d, JC–P = 73.8 Hz), 132.58 (d, JC–P = 71.0 Hz), 135.95,
146.23 (d, JCꢁP = 12.54 Hz), 170.88, 171.31; 31P NMR (200 MHz,
CDCl3) d 41.03; HRMS calcd for C31H33O4PS2: 564.1558, found:
564.1631. Anal. Calcd for C31H33O4PS2: C, 65.93; H, 5.89. Found: C,
65.90; H, 5.92.
15. Carta, P.; Puljic, P.; Robert, C.; Dhimane, A-L.; Fensterbank, L.;
Lacote, E.; Malacria, M. Org. Lett. 2007, 9, 1061.