Thiostannylation of arynes with stannyl sulfides: Synthesis and reaction of 2-(arylthio)arylstannanes

Article abstract of DOI:10.1039/b405883f

Arynes were found to insert into a sulfur-tin σ-bond of stannyl sulfides to give a variety of 2-(arylthio)arylstannanes, whose carbon-tin bonds were applicable to further transformations.

Full text of DOI:10.1039/b405883f

Thiostannylation of arynes with stannyl sulfides: synthesis and reaction
of 2-(arylthio)arylstannanes†
Hiroto Yoshida,* Tsuguaki Terayama, Joji Ohshita and Atsutaka Kunai*
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University,
Higashi-Hiroshima 739-8527, Japan. E-mail: yhiroto@hiroshima-u.ac.jp; akunai@hiroshima-u.ac.jp;
Fax: +81-82-424-5494; Tel: +81-82-424-7724.
Received (in Cambridge, UK) 21st April 2004, Accepted 27th May 2004
First published as an Advance Article on the web 8th July 2004
Arynes were found to insert into a sulfur–tin s-bond of stannyl
sulfides to give a variety of 2-(arylthio)arylstannanes, whose
carbon–tin bonds were applicable to further transformations.
simple benzyne, 4,5-disubstituted arynes (from 1b–1d) and
2,3-naphthalyne (from 1e) also provided the corresponding thios-
tannylation products (3ba–3ea) in good yields (entries 2–5). The
reaction of sterically congested 3,6-dimethoxybenzyne (from 1f) or
3,6-dimethylbenzyne (from 1g) proceeded efficiently as well,
giving 61% or 45% yield of the products (entries 6 and 7).
Furthermore, stannyl sulfides bearing a p-anisyl (2b) or o-tolyl (2c)
group could participate in the reaction (entries 8 and 9), and
(trimethylstannyl) phenyl sulfide (2d) reacted smoothly with
benzyne to afford 3ad in 56% yield (entry 10).5
We next investigated the thiostannylation of unsymmetrical
arynes (Scheme 1). Thus, when 4-substituted arynes (from 1h–1j)
were allowed to react with 2a, almost equal amounts of re-
gioisomeric products (3 and 3A) were produced, indicating that the
present reaction certainly proceeds through an aryne intermediate.
In marked contrast, the reaction of 4-fluorobenzyne (from 1k)
afforded 3ka as a major product, where the tributylstannyl moiety
was introduced into the meta-position of the fluoro substituent.
Methoxy or phenyl group in 3-substituted arynes (from 1l or 1m)
controlled the regioselectivities perfectly to offer 3la or 3ma as the
sole product, whereas the reaction of 3-methylbenzyne (from 1n)
gave a mixture of 3na and 3Ana in ca. 1 : 1 ratio.
Addition reactions of an element–element s-bond to arynes have
high synthetic significance, since both elements can be introduced
into the carbon–carbon triple bond simultaneously, leading to the
formation of polysubstituted arenes in a regioselective manner.1 In
particular, reactions using metallic reagents would be much more
attractive in that the resulting carbon–metal bond can be applied to
further carbon–carbon bond formation and/or introduction of a
functional group. However, only a limited number of reports2 has
been available on the additions of a metal–element bond to arynes
thus far, probably due to kinetic instability of arynes causing
undesirable side reactions. Recently, we have demonstrated that the
additions of a carbon–tin3a or silicon–silicon3b bond to arynes take
place selectively using a palladium catalyst. Herein we report that
a sulfur–tin bond of stannyl sulfides adds to arynes without an
added catalyst to provide synthetically useful 2-(arylthio)aryl-
stannanes straightforwardly (eqn. (1)). The thiostannylation prod-
ucts thus obtained are convertible into diverse polysubstituted
arenes by utilizing their carbon–tin bonds.
The thiostannylation would be triggered by a nucleophilic attack
of a sulfur atom of a stannyl sufide as depicted in Scheme 2.6,7 The
resulting zwitterion (4) then undergoes an intramolecular nucleo-
philic substitution at the stannyl moiety to afford the product (path
A). Owing to a strong electron-withdrawing effect of a fluorine
(1)
Benzyne, generated in situ from 2-(trimethylsilyl)phenyl triflate4
(1a) and a fluoride ion (KF/18-Crown-6), was treated with
(tributylstannyl) phenyl sulfide (2a) in THF at 0 °C (Table 1, entry
1). The reaction furnished the thiostannylation product, tributyl[2-
(phenylthio)phenyl]tin (3aa), in 54% yield along with diphenyl
sulfide (25%) and tributyl(2-fluorophenyl)tin (6%). In addition to
Table 1 Thiostannylation of symmetrical arynesa
Time Yield
Entry
R
1
Ar
Ph
RA
2
(h)
(%)b
3
1
2
3
4
5
6
7
8
9
H
1a
1b
Bu 2a
9
24
24
29
19
24
51
3
54
58
58
52
62
61
45
49
39
56
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ab
3ac
3ad
4,5-Me2
4,5-(CH2)3– 1c
4,5-(CH2)4– 1d
4,5-(CH)4– 1e
3,6-(MeO)2 1f
3,6-Me2
1g
1a
1a
1a
H
H
H
4-MeOC6H4 Bu 2b
2-MeC6H4 Bu 2c
Ph
4
4
10
Me 2d
a The reaction was carried out in THF (1 mL) at 0 °C using 1 (0.30 mmol),
2 (0.20 mmol), KF (0.30 mmol) and 18-Crown-6 (0.30 mmol). b Isolated
yield based on the stannyl sulfide.
† Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b4/b405883f/
Scheme 1 Thiostannylation of unsymmetrical arynes.
1980
C h e m . C o m m u n . , 2 0 0 4 , 1 9 8 0 – 1 9 8 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

atom in 4-fluorobenzyne, the developing negative charge at the
meta position (vs. para) is stabilized to a greater extent in the
transition state for the addition of a sulfur moiety to 4-fluor-
obenzyne, which leads to the predominant production of 3ka.8 In
contrast, electronic effects of other substituents in 4-subsituted
arynes are so slight that equal addition to both ends of the triple
bond takes place. The exclusive formation of 3la or 3ma would be
attributable to disfavored steric repulsion between a substituent
(MeO or Ph) in the aryne and 2a, which prevents the sulfur atom
approaching the ortho position of the substituent. In the case of
3-methylbenzyne, the steric effect should compete with the
electron-donating effect of the methyl group which prefers
generation of the anion in 4 at the meta position, and a mixture of
3na and 3Ana is formed.6 A diaryl sulfide should arise from a
nucleophilic attack of a fluoride ion to a stannyl moiety (path B),
and formation of a (2-fluoroaryl)tin can be ascribed to a reaction of
a 2-fluoroaryl anion with a stannyl electrophile (path C).9
Scheme 3 Transformation of the thiostannylation product.
Finally, synthetic utility of the thiostannylation product has been
demonstrated by transformation to variously substituted arenes
(Scheme 3). Thus, cross-coupling of 3aa with 4-nitroiodobenzene
gave 4a in 86% yield. Furthermore, homocoupling10 or iodolysis of
3aa afforded biaryl 4b or aryl iodide 4c, respectively.
In conclusion, we have disclosed that the thiostannylation of
arynes takes place with stannyl sulfides to offer diverse 2-(arylth-
io)arylstannanes straightforwardly, which can be utilized for the
synthesis of substituted arenes. Further studies on insertion
reactions of arynes into other element–element s-bonds are in
progress.
We thank Central Glass Co. Ltd. for a generous gift of
trifluoromethanesulfonic anhydride.
Notes and references
1 (a) Se–Se and Te–Te s-bond: N. Petragnani and V. G. Toscano, Chem.
Ber., 1970, 103, 1652; (b) S–S s-bond: J. Nakayama, T. Tajiri and M.
Hoshino, Bull. Chem. Soc. Jpn., 1986, 59, 2907; (c) N–CO s-bond: H.
Yoshida, E. Shirakawa, Y. Honda and T. Hiyama, Angew. Chem. Int.
Ed., 2002, 41, 3247.
2 (a) Si–C s-bond: Y. Sato, Y. Kobayashi, M. Sugiura and H. Shirai, J.
Org. Chem., 1978, 43, 199; (b) Sn–Cl s-bond: C.-L. Tseng, S.-H. Tung
and K.-M. Chang, Chem. Abs., 1964, 61, 7035; (c) B–O s-bond: C.-L.
Tseng, K.-M. Chang and S.-H. Tung, Chem. Abs., 1964, 61, 16084.
3 (a) H. Yoshida, Y. Honda, E. Shirakawa and T. Hiyama, Chem.
Commun., 2001, 1880; (b) H. Yoshida, J. Ikadai, M. Shudo, J. Ohshita
and A. Kunai, J. Am. Chem. Soc., 2003, 125, 6638.
4 Y. Himeshima, T. Sonoda and H. Kobayashi, Chem. Lett., 1983,
1211.
5 A diaryl sulfide (5–21%) and tributyl(2-fluoroaryl)tin (trace–9%) were
formed as by-products in all cases.
6 For a review on the nucleophilic couplings with arynes, see: S. V.
Kessar, in Comprehensive Organic Synthesis, ed. B. M. Trost and I.
Flemming, Pergamon Press, Oxford, 1991, vol. 4, pp. 483–515.
7 For reported examples on the nucleophilic couplings of sulfides with
arynes, see: (a) J. Nakayama, S. Takeue and M. Hoshino, Tetrahedron
Lett., 1984, 25, 2679; (b) G. M. Blackburn, W. D. Ollis, C. Smith and I.
O. Sutherland, J. Chem. Soc., Chem. Commun., 1969, 99.
8 A similar regioselectivity was observed in the nucleophilic couplings
with 4-chlorobenzyne: (a) J. F. Bunnett and C. Pyun, J. Org. Chem.,
1969, 34, 2035; (b) J. F. Bunnett and J. K. Kim, J. Am. Chem. Soc., 1973,
95, 2254.
9 Treatment of 2a with KF/18-Crown-6 did not give a thiophenoxide ion,
which would add to an aryne, if any. Moreover, destannylation of 3aa
did not occur in the presence of KF/18-Crown-6. These results prompt
us to propose path B in the formation of a diaryl sulfide.
10 E. Shirakawa, Y. Nakao, T. Tsuchimoto and T. Hiyama, Chem.
Commun., 2002, 1962.
Scheme 2 Plausible reaction pathways.
C h e m . C o m m u n . , 2 0 0 4 , 1 9 8 0 – 1 9 8 1
1981