Intermolecular radical addition of alkylthio- and arylthiodiphenylphosphines to terminal alkynes

Article abstract of DOI:10.1021/ol800059n

Intermolecular radical thiophosphination of terminal alkynes with alkylthio- and arylthlophosphlnes affords 1-thlo-2-phosphlno-1-alkenes In good yields. The addition reaction proceeds predominantly In an anti fashion to yield E Isomers.

Full text of DOI:10.1021/ol800059n

ORGANIC
LETTERS
2008
Vol. 10, No. 6
1155-1157
Intermolecular Radical Addition of
Alkylthio- and
Arylthiodiphenylphosphines to Terminal
Alkynes
Tatsuya Wada, Azusa Kondoh, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
yori@orgrxn.mbox.media.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received January 9, 2008
ABSTRACT
Intermolecular radical thiophosphination of terminal alkynes with alkylthio- and arylthiophosphines affords 1-thio-2-phosphino-1-alkenes in
good yields. The addition reaction proceeds predominantly in an anti fashion to yield E isomers.
Radical additions of heteroatom-heteroatom bonds to carbon-
carbon multiple bonds are powerful methods to install two
heteroatoms efficiently in one operation. Among them,
radical dichalcogenation reactions of carbon-carbon multiple
bond have been extensively studied1 and are useful for the
synthesis of alkenyl sulfides,2 selenides,3 and tellurides.4 On
the other hand, little is known for radical additions of
phosphorus-heteroatom bonds, despite the importance of
organophosphorus compounds in organic chemistry.5 Tetra-
organodiphosphines add to terminal alkynes to yield (E)-
1,2-diphosphino-1-alkenes.6 Very recently, an example of
intramolecular radical thiophosphinylation was reported.7,8
Here we report intermolecular thiophosphination of terminal
alkynes.
A mixture of 1-dodecyne (1a), diphenyl(phenylthio)-
phosphine (2a),9 and 1,1′-bis(cyclohexanecarbonitrile) (V-
40) was heated in benzene at reflux for 14 h (Scheme 1).
The reaction proceeded predominantly in an anti fashion,
yielding (E)-2-diphenylphosphino-1-phenylthio-1-dodecene
(3a) as the main product. Since trivalent phosphine 3a was
sensitive to oxygen, the product was isolated as phosphine
sulfide after treatment of the reaction mixture with elemental
sulfur. The phosphine sulfide 4a was obtained in 75% NMR
yield as a 94:6 mixture of E/Z isomers. Neither regioisomer
1,2-bis(phenylthio)-1-dodecene nor 1,2-bis(diphenylthiophos-
phinyl)-1-dodecene was detected. The use of AIBN, instead
of V-40, resulted in a lower yield (64% based on 31P NMR).
(1) Review: Ogawa, A. J. Synth. Org. Chem., Jpn. 1995, 53, 869-880.
(2) (a) Heiba, E. I.; Dessau, R. M. J. Org. Chem. 1967, 32, 3837-3840.
(b) Benati, L.; Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin Trans.
1 1991, 2103-2109.
(3) (a) Back, T. G.; Krishna, M. V. J. Org. Chem. 1988, 53, 2533-
2536. (b) Ogawa, A.; Yokoyama, H.; Yokoyama, K.; Masawaki, T.; Kambe,
N.; Sonoda, N. J. Org. Chem. 1991, 56, 5721-5723. (c) Ogawa, A.; Takami,
N.; Sekiguchi, M.; Yokoyama, H.; Kuniyasu, H.; Ryu, I.; Sonoda, N. Chem.
Lett. 1991, 2241-2242. (d) Tsuchii, K.; Doi, M.; Hirao, T.; Ogawa, A.
Angew. Chem., Int. Ed. 2003, 42, 3490-3493. (e) Renaud, P. Top. Curr.
Chem. 2000, 208, 81-112.
(6) (a) Morse, J. G.; Mielcarek, J. J. J. Fluorine Chem. 1988, 40, 41-
49. (b) Tzschach, V. A.; Baensch, S. J. Prakt. Chem. 1971, 313, 254-258.
(c) Sato, A.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2005, 44,
1694-1696.
(4) (a) Ogawa, A.; Yokoyama, K.; Yokoyama, H.; Obayashi, R.; Kambe,
N.; Sonoda, N. J. Chem. Soc., Chem. Commun. 1991, 1748-1750. (b)
Ogawa, A.; Yokoyama, K.; Obayashi, R.; Han, L.-B.; Kambe, N.; Sonoda,
N. Tetrahedron 1993, 49, 1177-1188.
(5) (a) Murphy, P. J. In Organophosphorus Reagents; Murphy, P. J.,
Ed.; Oxford University Press: New York; 2004, Chapter 1. (b) Quin, L.
D. Guide to Organophosphorus Chemistry; John Wiley & Sons: New York;
2000.
(7) Carta, P.; Puljic, N.; Robert, C.; Dhimane, A.-L.; Fensterbank, L.;
Lacoˆte, E.; Malacria, M. Org. Lett. 2007, 9, 1061-1063.
(8) Barton et al. reported radical decarboxylative phosphorylation involv-
ing homolytic substitution at phosphorus with displacement of a sulfur-
centered radical. Barton, D. H. R.; Bridon, D.; Zard, S. Z. Tetrahedron
Lett. 1986, 27, 4309-4312.
(9) Thiophosphines were readily synthesized from chlorodiphenylphos-
phine and thiols. They are stable under air.
10.1021/ol800059n CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/28/2008

under the reaction conditions. The E configuration of the
major isomer of 4 was deduced from the X-ray crystal-
lographic analysis of the major isomer of 4f. Attempts on
addition across internal alkynes resulted in failure.
Scheme 1. Intermolecular Radical Thiophosphination of
1-Dodecyne with Diphenyl(phenylthio)phosphine
(4-Methoxyphenylthio)diphenylphosphine (2b) added to
phenylacetylene (1d) as smoothly as 2a (Scheme 2, eq 1).
Scheme 2. Addition of Various Thiophosphines
Increasing the amount of thiophosphine 2a improved the 31
NMR yield of 4a to 86%.10
P
A variety of 1-alkynes underwent the radical thiophos-
phination reaction (Table 1). Cyclohexylacetylene (1b) also
Table 1. Intermolecular Radical Thiophosphination of
Terminal Acetylenes with 2a
isolated
entry
1
R
2a/equiv
4
yield/%
E/Z
1
2
3
4
5
6
7
8
9
1a nC10H21
1b cC6H11
1c tBu
1d Ph
1e 4-MeOC6H4
2.5
2.5
2.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2.5
4a
4b
4c
4d
4e
4f
4g
4h
4i
75
61
trace
83
75
85
69
73
69
80
94:6
88:12
Alkylthiophosphine 2c as well as arylthiophosphines 2a and
2b reacted with terminal alkynes (eqs 2 and 3). The addition
of 2c to alkyl-substituted alkyne 1a was less efficient (eq
3). The reaction of phenylacetylene (1d) with bulky (tert-
butylthio)diphenylphosphine (2d) proceeded to afford the
adduct 8 in moderate yield (eq 4).
89:11
89:11
89:11
85:15
85:15
84:16
90:10
94:6
1f
2-MeOC6H4
1g 4-AcC6H4
1h 4-MeOCOC6H4
The high E selectivity of the reaction can be explained as
outlined in Scheme 3. Thiophosphine 2 would approach the
1i
1j
4-CF3C6H4
4-H2NC6H4
10
11
4j
4k
1k HO(CH2)3
66
Scheme 3. Origin of the Stereoselectivity
reacted with 2a to afford 4b in good yield (entry 2), although
tert-butylacetylene (1c) failed to react (entry 3). Not only
alkyl-substituted acetylenes but also aryl-substituted ones
participated in the reaction (entries 4-10). The arylacetylenes
(1d-j) were more reactive than 1a-c, which allowed us to
use a smaller amount of 2a (1.5 equiv). It is worth noting
that functional groups such as keto (entry 7), ester (entry 8),
amino (entry 10), and hydroxy (entry 11) were compatible
(10) Experimental Procedure. Under an atmosphere of argon,
1-dodecyne (1a, 83 mg, 0.50 mmol), diphenyl(phenylthio)phosphine (2a,
0.37 g, 1.25 mmol), and V-40 (24 mg, 0.10 mmol) were dissolved in benzene
(1.5 mL) in a reaction flask. The mixture was heated at reflux for 14 h.
After the mixture was cooled to room temperature, crystalline sulfur (0.058
g, 1.8 mmol) was added. The mixture was stirred for 1 h. The solvent was
removed under reduced pressure to leave an oil. A P NMR analysis of the
crude product by using trimethyl phosphate as an internal standard showed
the formation of 4a in 86% yield. Chromatographic purification on silica
gel by using hexane/ethyl acetate ) 20:1 as an eluent followed by further
purification with gel permeation chromatography afforded 4a (0.19 g, 0.38
mmol) in 75% yield (E/Z ) 94:6).
intermediary alkenyl radical more readily from the opposite
side of the R2S group of the radical to avoid the steric
repulsion.11
Radical desulfidation of the phosphine sulfides with tris-
(trimethylsilyl)silane (TTMSS) was facile to yield the parent
(11) Stereochemistry of Radical Reactions; Curran, D. P., Porter, N. A.,
Giese, B., Eds.; VCH Publishers: New York, 1995; Chapter 6.3.
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Org. Lett., Vol. 10, No. 6, 2008

resulted in the formations of significant amounts of the
corresponding phosphine oxide.13 The sulfidation-desulfi-
dation two-step protocol is quite effective to prevent the
formation of the phosphine oxide.
Scheme 4. Radical Desulfidation of Phosphine Sulfides with
TTMSS
In summary, we have devised intermolecular radical
thiophosphination of terminal alkynes. In light of the
importance of organophosphorus compounds, the products
or their derivatives can be useful as ligands, reagents, and
building blocks for organic synthesis.
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Government
of Japan. We thank Prof. Masaki Shimizu (Department of
Material Chemistry, Kyoto University) for generous help for
the X-ray crystallographic analysis. A.K. acknowledges JSPS
for financial support.
phosphines almost quantitatively (Scheme 4).12 Treatment
of 4f and 6 with TTMSS in the presence of AIBN in
refluxing benzene provided the corresponding phosphines
3f and 9, respectively. During the desulfidation, no isomer-
izations of the carbon-carbon double bonds took place.
Notably, attempts to isolate 3f immediately after the thio-
phosphination of 1f with 2a without adding sulfur always
Supporting Information Available: Characterization
data of the products. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL800059N
(12) Romeo, R.; Wozniak, L. A.; Chatgilialoglu, C. Tetrahedron Lett.
2000, 41, 9899-9902.
(13) Probably, the use of a glovebox filled with inert gas would allow
for direct isolation of 3f.
Org. Lett., Vol. 10, No. 6, 2008
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