Synthesis of aryl stannanes from silyl triflates via aryne intermediates

Article abstract of DOI:10.1055/s-0030-1259311

Aryl stannanes are easily accessible from o-silylated aryl triflates in the presence of KF and Bu³SnH. The corresponding arynes are formed in situ, and undergo clean hydrostannation to give a mixture of the regioisomeric aryl stannanes. The whole reaction sequence can also be carried out as a one-pot reaction under microwave irradiation. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1259311

LETTER
345
Synthesis of Aryl Stannanes from Silyl Triflates via Aryne Intermediates
A
ryl Stannanes fr
.
om Silyl
Tri
V
flates asantha Lakshmi, Ulrike K. Wefelscheid, Uli Kazmaier*
Institut für Organische Chemie, Universität des Saarlandes, 66123 Saarbrücken, Germany
Fax +49(681)3022409; E-mail: u.kazmaier@mx.uni-saarland.de
Received 25 November 2010
quire reaction temperatures of around 50 °C, here the re-
action was complete after two hours at room temperature,
probably because of the high reactivity of the aryne.
Abstract: Aryl stannanes are easily accessible from o-silylated aryl
triflates in the presence of KF and Bu3SnH. The corresponding
arynes are formed in situ, and undergo clean hydrostannation to
give a mixture of the regioisomeric aryl stannanes. The whole reac-
tion sequence can also be carried out as a one-pot reaction under mi-
crowave irradiation.
We also investigated the influence of other fluoride sourc-
es (entries 2–4). Comparable results were obtained with
CsF in MeCN, but the use of tetrabutylammonium fluo-
ride (TBAF) and KF in the presence of tetrabutylammoni-
um bromide (TBAB) as phase-transfer catalyst gave
significantly lower yields and required longer reaction
times. This clearly indicates that aryne formation is the
rate determining step. Because the very fast and clean re-
action at room temperature was quite surprising, a control
experiment was conducted without the Mo catalyst to es-
tablish its role (entry 5). Indeed, nearly the same result
was obtained with Bu3SnH alone.
Key words: arynes, aryl stannanes, hydrostannation, one-pot reac-
tion, Stille coupling
Vinyl stannanes are interesting building blocks in organic
synthesis,1 and are easily available, for example, by hy-
drostannations of alkynes. In general, these hydrometalla-
tions can be carried out under radical or transition-metal-
catalyzed conditions.2 In principle, aryl stannanes should
be accessible by the same protocol using arynes. Based on
their high reactivity, the tin hydride addition should be a Table 1 Preparation of Phenylstannane 2a
relatively fast process. Surprisingly, to the best of our
knowledge, such a direct synthesis of aryl stannanes via
hydrostannation of arynes is not yet been described in the
TMS
Bu3SnH (1.2 equiv)
SnBu3
F–-source (2 equiv)
reaction condition
OTf
literature. In general, aryl stannanes are obtained from
1a
2a
aryl halides via halogen–metal exchange (with Mg,3 Li4 or
Entry F– source
Reaction conditions
Yield
(%)
Zn5) and subsequent transmetallation with R3SnCl. Alter-
natively, aryl stannanes can be obtained by Pd-catalyzed
6
coupling of aryl halides with (R3Sn)2 or via radical-
1
2
3
4
5
KF/18-C-6
CsF
MoBI3 (3 mol%), THF, r.t., 2 h
MoBI3 (3 mol%), MeCN, r.t., 2 h
90
80
60
40
85
nucleophilic substitution of triorganostannyl anions and
aryl chlorides, aryl phosphates or aryl ammonium salts.7
Furthermore, Pd-catalyzed distannylations of arynes with
(R3Sn)2 have been described.8
TBAF·3H2O MoBI3 (3 mol%), THF, r.t., 4 h
KF/TBAB
KF/18-C-6
MoBI3 (3 mol%), THF, r.t., 16 h
THF, r.t., 2 h
Based on our interest in Mo-catalyzed hydrostannations
of alkynes,9 we were interested to see if such a hydromet-
allation might also work with arynes. Arynes are easily
accessible from o-silylated aryl triflates,10 which were
synthesized according to a known procedure from the cor-
responding o-bromophenols via O-silylation and a se-
quence of lithiation/silyl-migration/triflation.11
To assess the generality of this observation, we investigat-
ed a wide range of other substituted silyl triflates 1
(Table 2). The presence of 10 mol% hydroquinone as rad-
ical inhibitor showed a marginal positive influence on the
yields. As expected, regioisomeric mixtures of aryl stan-
nanes 2 and 2¢ were obtained, which clearly indicates that
the proposed aryne is the real intermediate. For example,
the two regioisomeric triflates 1b and 1c, which generate
the same aryne, gave comparable results, although the
product ratio was slightly different. In general, no signifi-
cant regioselectivity was observed (as expected), except
for the phenyl-substituted derivative 1g and the sterically
extremely hindered substrate 1f. In the latter case the yield
dropped significantly, but the sterically least hindered
stannane 2f was obtained as the sole product.
We began our investigations with the simple silyl triflate
1a, which does not give regioisomers in the hydrostanna-
tion step. In general, arynes are prepared in the presence
of fluoride, preferentially under the influence of crown
ethers. Therefore, we used these conditions in our first ex-
periments (Table 1). With our hydrostannation catalyst
Mo(CO)3(CNt-Bu)3 (MoBl3), a very clean reaction was
observed, giving rise to phenylstannane 2a in excellent
yield. Although hydrostannations of alkynes in general re-
SYNLETT 2011, No. 3, pp 0345–0348
x
x.
x
x.
2
0
1
1
Advanced online publication: 13.01.2011
DOI: 10.1055/s-0030-1259311; Art ID: G36110ST
© Georg Thieme Verlag Stuttgart · New York

346
B. V. Lakshmi et al.
LETTER
Table 2 Preparation of Aryl Stannane 2
TMS
SnBu3
Bu3SnH (1.2 equiv)
KF/18-C-6 (2 equiv)
OTf
hydroquinone (10 mol%)
THF, r.t., 2–3 h
R
R
1
2
Entry
Triflate
Stannanes
Ratio 2/2¢
Yield (%)
80
OMe
MeO
SiMe3
OTf
MeO
MeO
1
2
3
4
5
6
58:42
SnBu3
SnBu3
SnBu3
1b
2b
2b'
2b'
2d'
OMe
SiMe3
OTf
68:32
54:46
68:32
100:0
84:16
78
76
81
30
60
MeO
SnBu3
1c
2b
Me
Me
SiMe3
OTf
Me
SnBu3
SnBu3
Me
1d
2d
Me
Me
OTf
SnBu3
Me
SiMe3
Me
SnBu3 Me
2e
2e'
1e
t-Bu
t-Bu
t-Bu
OTf
SnBu3
t-Bu
SiMe3
t-Bu
Ph
SnBu3 t-Bu
Ph
2f
2f'
1f
Ph
OTf
SnBu3
SiMe3
SnBu3
2g
2g'
1g
Cl
Cl
Cl
OTf
SnBu3
7
8
63:36
58:42
48
60
Cl
SiMe3
Cl
SnBu3
Cl
2h
2h'
1h
SiMe3
SnBu3
OTf
SnBu3
2i
2i'
1i
With these aryl stannanes in hand, several Stille couplings tions, the coupling under microwave irradiation was also
were investigated to evaluate the synthetic potential of investigated. Although the yield of 5 increased only mod-
this method (Scheme 1). Tin–iodide exchange and the erately (60%) the reaction was finished within 30 minutes,
cross coupling with p-nitroiodobenzene worked smooth- which is a significant improvement.
ly, while the best results in the Stille coupling were
Therefore, we next tried to combine the aryl stannane syn-
obtained in the presence of CuI using N,N-dimethylform-
thesis and the subsequent cross coupling reaction into a
amide (DMF) as a solvent.12 Surprisingly, the reaction
one-pot protocol (Scheme 2).13 When silyl triflate 1a was
with benzoyl chloride was rather sluggish; even after 16
irradiated in the microwave oven, complete consumption
hours the starting material could be recovered and the
of the starting material was observed after 15 minutes, and
yield did not exceed 50%. To optimize the reaction condi-
Synlett 2011, No. 3, 345–348 © Thieme Stuttgart · New York

LETTER
Aryl Stannanes from Silyl Triflates
347
In conclusion, the developed procedure enables arynes to
be formed in situ, which then undergo clean hydrostanna-
tion to give a mixture of the regioisomeric aryl stan-
nanes.15 The reaction can also be run as a one-pot
sequence under microwave irradiation.
O2N
3
O2N
I
[allylPdCl]2, Ph3P, CuI
DMF, 60 °C, 16 h, 94%
SnBu3
I2, CH2Cl2
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
I
r.t., 2 h, 85%
4
PhCOCl
[allylPdCl]2, PPh
Acknowledgment
THF, MW, 150 °C, 30 min
60%
THF, 60 °C, 16 h
50%
This work was supported by the Deutsche Forschungsgemeinschaft
and by the Fonds der Chemischen Industrie.
O
References and Notes
5
(1) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508;
Angew. Chem. 1986, 98, 504. (b) Davies, A. G. In
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Organotin Chemistry; VCH: Weinheim, 1997.
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Chem. Rev. 2000, 100, 3257. (b) Trost, B. M.; Ball, Z. T.
Synthesis 2005, 853; and references cited therein.
(3) Hayashi, T.; Ishigedani, M. Tetrahedron 2001, 57, 2589.
(4) (a) Gilman, H.; Rosenberg, S. D. J. Am. Chem. Soc. 1953,
75, 2507. (b) Earbon, C.; Seconi, G. J. Chem. Soc., Perkin
Trans. 2 1976, 925. (c) Iddon, B.; Lim, B. L. J. Chem. Soc.,
Perkin Trans. 1 1983, 271.
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Scheme 1 Reactions of phenylstannane
aryl stannane 2a was isolated in 90% yield. A similar
reaction with subsequent addition of benzoyl chloride and
the Pd catalyst gave the expected benzophenone in the
same yield as in the reaction of benzoyl chloride with pu-
rified stannane 2a.
Bu3SnH, KF/18-C-6
SiMe3
hydroquinone (10 mol%)
MW, 100 °C, 15 min, 90%
OTf
SnBu3
1a
2a
1) Bu3SnH, KF/18-C-6
hydroquinone (10 mol%)
MW, 100 °C, 15 min
O
SiMe3
OTf
2) PhCOCl, [allylPdCl]2
Ph3P, MW, 150 °C
30 min, 60%
(7) (a) Lockhart, M. T.; Chopa, A. B.; Rossi, R. A.
J. Organomet. Chem. 1999, 582, 229. (b) Chopa, A. B.;
Lockhart, M. T.; Silbestri, G. Organometallics 2001, 20,
3358. (c) Chopa, A. B.; Lockhart, M. T.; Silbestri, G.
Organometallics 2000, 19, 2249.
1a
5
Scheme 2 One-pot synthesis of phenylstannane and coupling
The major drawback of this protocol is the formation of
regioisomeric products, which, in some cases (highly non-
polar compounds), cannot be separated by chromatogra-
phy. The stannylated toluenes 2d and 2d¢ are examples of
such an inseparable mixture. Therefore, the Stille cou-
pling conditions were applied to the isomeric mixtures.
For example, Stille coupling with iodobenzene under a
CO atmosphere14 gave rise to the corresponding regioiso-
meric ketones 6 and 7, which could then be readily sepa-
rated (Scheme 3). In this case, DMF was also the solvent
of choice, giving a nearly quantitative yield of the cou-
pling product.
(8) (a) Yoshida, H.; Tanino, K.; Ohshita, J.; Kunai, A. Angew.
Chem. Int. Ed. 2004, 43, 5052; Angew. Chem. 2004, 116,
5162. (b) Yoshida, H.; Tanino, K.; Ohshita, J.; Kunai, A.
Chem. Commun. 2005, 5678.
(9) (a) Kazmaier, U.; Schauß, D.; Pohlman, M. Org. Lett. 1999,
1, 1017. (b) Kazmaier, U.; Pohlman, M.; Schauß, D. Eur. J.
Org. Chem. 2000, 2761. (c) Kazmaier, U.; Schauß, D.;
Pohlman, M.; Raddatz, S. Synthesis 2000, 914.
(d) Kazmaier, U.; Schauß, D.; Raddatz, S.; Pohlman, M.
Chem. Eur. J. 2001, 7, 456. (e) Braune, S.; Kazmaier, U.
J. Organomet. Chem. 2002, 641, 26. (f) Braune, S.;
Pohlman, M.; Kazmaier, U. J. Org. Chem. 2004, 69, 468.
(g) Kazmaier, U.; Dörrenbächer, S.; Wesquet, A.; Lucas, S.;
Kummeter, M. Synthesis 2007, 320. (h) Lakshmi, B. V.;
Kazmaier, U. Synlett 2010, 407.
Me
Me
(10) (a) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett.
1983, 1211. (b) Peña, D.; Escudero, S.; Pérez, D.; Guitián,
E.; Castedo, L. Angew. Chem. Int. Ed. 1998, 37, 2659;
Angew. Chem. 1998, 110, 2804. For this and other methods
to generate arines and for applications see the following
reviews:. (c) Pellissier, H.; Santelli, M. Tetrahedron 2003,
59, 701. (d) Yoshida, H.; Ohshita, J.; Kunai, A. Bull. Chem.
Soc. Jpn. 2010, 83, 199.
Me
Me
PhI, CO, DMF
[allylPdCl]2, PPh
+
+
1) r.t., 15 min
2) 65 °C, 16 h
95%
SnBu3
COPh
SnBu3
COPh
2d
2d'
6
7
Scheme 3 Carbonylative Stille coupling of stannane mixture 2d
Synlett 2011, No. 3, 345–348 © Thieme Stuttgart · New York

348
B. V. Lakshmi et al.
LETTER
(11) (a) Himeshima, Y.; Kobayashi, H.; Sonoda, T. J. Am. Chem.
Soc. 1985, 107, 5286. (b) Peña, D.; Pérez, D.; Guitián, E.;
Castedo, L. J. Org. Chem. 2000, 65, 6944. (c) Peña, D.;
Cobas, A.; Pérez, D.; Guitián, E. Synthesis 2002, 1454.
(d) Zhijian, L.; Larock, R. C. J. Org. Chem. 2006, 71, 3198.
(12) Yoshida, H.; Terayama, T.; Ohshita, J.; Kunai, A. Chem.
Commun. 2004, 1980.
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(15) General procedure for the synthesis of aryl stannanes 2:
In a Schlenk flask, silyl triflate 1 (0.33 mmol) was dissolved
in THF (3 mL) and hydroquinone (0.033 mmol, 3.6 mg),
tributyltin hydride (0.10 mL, 0.39 mmol), 18-crown-6 (174
mg, 0.660 mmol), and KF (37 mg, 0.66 mmol) were added
sequentially. The resulting mixture was stirred at 20 °C for
2–3 h. The reaction mixture was then diluted with ethyl
acetate, filtered through Celite, and concentrated. Column
chromatography on silica gel (pentane or hexane with 1
vol% Et3N) gave aryl stannanes 2 as colorless oils.
One-pot synthesis of phenyl stannane and Stille coupling
with benzoyl chloride: In a microwave vial, silyl triflate 1a
(100 mg, 0.330 mmol) was dissolved in THF (2.0 mL) and
hydroquinone (0.033 mmol, 3.6 mg), tributyltin hydride
(0.089 mL, 0.33 mmol), 18-crown-6 (174 mg, 0.660 mmol),
and KF (37 mg, 0.66 mmol) were added sequentially. The
resulting mixture was subjected to microwave irradiation for
15 min at 100 °C (max. 200 W). Separately, in a round-
bottom flask, [(allyl)PdCl]2 (0.0033 mmol, 1.2 mg) and Ph3P
(3.5 mg, 0.013 mmol) were dissolved in THF (2 mL) and
stirred at r.t. for 5 min. The resulting solution and benzoyl
chloride (70 mg, 0.49 mmol) were added to the crude
reaction mixture in the microwave vial, which was subjected
to further microwave irradiation at 150 °C for 30 min (max.
200 Watt). The reaction mixture was diluted with saturated
aq KF (3 mL) and stirred for 30 min. The mixture was
extracted with Et2O and the combined organic layers were
dried with NaSO4, filtered and concentrated under reduced
pressure. Purification of the residue by column
chromatography on silica gel (hexane–EtOAc, 19:1)
afforded benzophenone as a colorless solid (37 mg, 60%).
Synlett 2011, No. 3, 345–348 © Thieme Stuttgart · New York

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