Gold-catalyzed cyclization of (ortho-alkynylphenylthio)silanes: Intramolecular capture of the vinyl-au intermediate by the silicon electrophile

Article abstract of DOI:10.1021/ol701951n

The gold-catalyzed cyclization of (ortho-alkynylphenylthio)silanes 1 produced the corresponding 3-silylbenzo[b]thiophenes 2 in good to excellent yields. For example, the reaction of [2-(1-pentynyl)phenylthio] triisopropylsilane 1a, [2-(p-anisylethynyl)phe

Full text of DOI:10.1021/ol701951n

ORGANIC
LETTERS
2007
Vol. 9, No. 20
4081-4083
Gold-Catalyzed Cyclization of
(ortho-Alkynylphenylthio)silanes:
Intramolecular Capture of the Vinyl
−Au
Intermediate by the Silicon Electrophile
Itaru Nakamura,* Takuma Sato, Masahiro Terada, and Yoshinori Yamamoto
Department of Chemistry, Graduate School of Science, Tohoku UniVersity,
Sendai 980-8578 Japan
itaru-n@mail.tains.tohoku.ac.jp
Received August 10, 2007
ABSTRACT
The gold-catalyzed cyclization of (ortho-alkynylphenylthio)silanes 1 produced the corresponding 3-silylbenzo[b]thiophenes 2 in good to excellent
yields. For example, the reaction of [2-(1-pentynyl)phenylthio]triisopropylsilane 1a, [2-(p-anisylethynyl)phenylthio]triisopropylsilane 1e, and
[2-(phenylethynyl)phenylthio]triisopropylsilane 1g in the presence of 2 mol % of AuCl in toluene at 45
°
C gave 2a, 2e, and 2g in 98, 99, and
97% yields, respectively. This reaction proceeds through intramolecular capture of the vinyl−Au intermediate by the silicon electrophile,
so-called silyldemetalation.
Gold-catalyzed reactions have rapidly gained great impor-
tance as a synthetic method in organic chemistry.1 For a large
Scheme 1. Capture of the Vinyl-Gold Intermediate by
Various Electrophiles: (a) Proton (Protodemetalation), (b)
Carbon Electrophiles, (c) Sulfonyl Groups, and (d) Silicon
Electrophiles (Silyldemetalation)
number of gold-catalyzed reactions, the catalytic cycle is
completed by trapping of a vinyl-Au intermediate with a
proton, so-called protodemetalation (Scheme 1, type a).1a,2
Recently, several groups, including ourselves, have disclosed
that such intermediates can also be captured by carbon
electrophiles, such as iminium, R-alkoxyalkyl, allyl, and
benzyl groups, in an intramolecular fashion (type b).3 We
also recently reported that a vinyl-Au intermediate can be
(1) For a review of Au-catalyzed reactions: (a) Gorin, D. J.; Toste, F.
D. Nature 2007, 446, 395. (b) Fu¨rstner, A.; Davies, P. W. Angew. Chem.,
Int. Ed. 2007, 46, 3410. (c) Hashmi, A. S. K.; Huchings, G. J. Angew.
Chem., Int. Ed. 2006, 45, 7896. (d) Zhang, L.; Sun, J.; Kozmin, S. A. AdV.
Synth. Catal. 2006, 348, 2271. (e) Asao, N. Synlett 2006, 1645. (f)
Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555. (g) Ma, S.;
Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200. (h) Hashmi, A. S. K.
Angew. Chem., Int. Ed. 2005, 44, 6990.
(2) For example: (a) Horino, Y.; Luzung, M. R.; Toste, F. D. J. Am.
Chem. Soc. 2006, 128, 11364. (b) Buzas, A. K.; Istrate, F. M.; Gagosz, F.
Angew. Chem., Int. Ed. 2007, 46, 1141. (c) Lee, J. H.; Toste, F. D. Angew.
Chem., Int. Ed. 2007, 46, 912. (d) Zhang, L.; Kozmin, S. A. J. Am. Chem.
Soc. 2005, 127, 6962.
trapped by sulfur electrophiles in a gold-catalyzed intramo-
lecular aminosulfonylation reaction (type c).4 In this com-
munication, we report that a vinyl-Au intermediate can be
intramolecularly captured by silicon electrophiles (type d);
the gold-catalyzed cyclization of (ortho-alkynylphenylthio)-
(3) (a) Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804. (b) Nakamura,
I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 4473. (c)
Dube´, P.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 12062.
(4) Nakamura, I.; Yamagishi, U.; Song, D.; Konta, S.; Yamamoto, Y.
Angew. Chem., Int. Ed. 2007, 46, 2284.
10.1021/ol701951n CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/05/2007

Table 1. Cyclization of (ortho-Alkynylphenylthio)silanes 1a
entry
1
R1
SiR2
AuCl (mol %)
time(h)
2
yield (%)b
3
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
n-Pr
Cy
Si(i-Pr)3
Si(i-Pr)3
Si(i-Pr)3
Si(i-Pr)3
Si(i-Pr)3
Si(i-Pr)3
Si(i-Pr)3
Si(i-Pr)3
Si(i-Pr)3
2
25
10
5
2
10
2
10
10
2
5
21
18
5
2a
2b
2c
2d
2e
2f
2g
2h
2i
98
44
89
99
99
96
97
60
90
4-i-Pr2NC6H4
2,4-(MeO)2C6H3
4-MeOC6H4
4-MeC6H4
Ph
4-F3CC6H4
2-(1-methylpyrrolyl)
n-Hex
8
24
19
21
18
6
10
11
1j
1k
Si(i-Pr)2(s-Bu)
SiPh3
2j
2k
quant
40
n-Pr
10
2
a
b
The reaction of 1 (0.4 mmol) was carried out in the presence of catalytic amounts of AuCl in toluene (1 mL) at 45 °C. Isolated yield.
silanes 1 produced 3-silylbenzo[b]thiophenes 2 in good to
The reaction mechanism for this gold-catalyzed cyclization
excellent yields (eq 1).
of 1 is illustrated in Scheme 2. The Lewis acidic gold(I)
Scheme 2. Plausible Mechanism
The results are summarized in Table 1. The reaction of
[2-(1-pentynyl)phenylthio]triisopropylsilane 1a in the pres-
ence of 2 mol % of AuCl in toluene at 45 °C for 5 h gave
(2-propylbenzo[b]thiophen-3-yl)triisopropylsilane 2a in 98%
yield (entry 1). The use of AuCl3, AuCl(CO), and AuBr3 as
the catalyst, instead of AuCl, gave 2a in lower yields,
whereas other metal complexes, such as PtCl2, Pt(PPh3)4,
PdCl2, CuCl2, Ag(OTf), and InCl3, did not promote the
present reaction at all. The reaction of 1a using benzene,
hexane, CH2Cl2, or ethyl acetate, instead of toluene, gave
2a in similar yields, whereas the use of other solvents, such
as acetonitrile and THF, was not effective. The reaction of
1a at 25 °C afforded 2a in 63% yield. A higher catalyst
loading (25 mol %) was required for the reaction of 1b
bearing a bulky cyclohexyl group at R1 to obtain 2b in a
moderate yield (entry 2). The reaction of 1c-f having
electron-rich aromatic rings at the alkynyl moiety gave the
corresponding products 2c-f in excellent yields, whereas
the reaction of 1h bearing an electron-deficient aromatic ring
at R1 produced 2h in a lower yield (entries 3-8). A pyrrole
ring was tolerated in this reaction, as migration of the silyl
group to the pyrrole ring was not observed at all (entry 9).
A (2-butyl)diisopropylsilyl group showed reactivity similar
to a triisopropylsilyl group, and the reaction of 1k bearing a
triphenylsilyl group afforded the desired product 2k in a
lower yield (entries 10 and 11). The reaction of a (6-
alkynylbenzodioxol-5-ylthio)silane 1l proceeded smoothly,
affording the tricyclic compound 2l in 72% yield (eq 2).
chloride first coordinates to the alkynyl moiety of 1.5 The
resulting electron-deficient triple bond of 3 undergoes
intramolecular nucleophilic attack by the sulfur atom, leading
to the silylsulfonium intermediate 4. A [1,3] migration of
the silyl group and subsequent elimination of the AuCl, so-
called silyldemetalation, gives the product 2.6,7
Interestingly, crossover of the silyl group was observed
when we mixed 1a and 1j under the standard reaction
conditions. A resulting 1:1:1:1 mixture of normal products
2a and 2j and crossover products 2m and 2n was obtained
quantitatively (Scheme 3, a). We, however, did not observe
any crossover of the silyl group between the starting materials
by GC-MS during the progress of the reaction. This result
contrasts with the crossover experiment of the gold-catalyzed
intramolecular carbothiolation:3b the reaction of a mixture
(5) Hu¨ttel, R.; Forkl, H. Chem. Ber. 1972, 105, 1664.
(6) Migration of silyl groups: (a) Kira, M.; Iwamoto, T. In Chemistry
of Silicon Compounds; Rappoport, Z., Apeloig, Y., Eds.; John Wiley &
Sons Ltd.: Chichester, UK, 2001; p 853. (b) Anderson, G.; Cameron, D.
W.; Feutrill, G. I.; Read, R. W. Tetrahedron Lett. 1981, 22, 4347. (c)
Yamabe, T.; Nakamura, K.; Shiota, Y.; Yoshizawa, K.; Kawauchi, S.;
Ishikawa, M. J. Am. Chem. Soc. 1997, 119, 807. (d) Takahashi, M.; Kira,
M. J. Am. Chem. Soc. 1997, 119, 1948. (e) Ward, B. D.; Orde, G.; Clot,
E.; Cowley, A. R.; Gade, L. H.; Mountford, P. Organometallics 2005, 24,
2368. (f) Seregin, I. V.; Gevorgyan, V. J. Am. Chem. Soc. 2006, 128, 12050.
4082
Org. Lett., Vol. 9, No. 20, 2007

Scheme 3. Crossover Experiments (a) Thiosilylation and (b) Carbothiolation
product 2h in a lower yield (Table 1, entry 8). On the
of the O,S-acetals 5a and 5b in the presence of catalytic
amounts of AuCl gave the products 6a and 6b derived from
each starting material, and only trace amounts of the
crossover products 6c and 6d were observed by GC-MS
(Scheme 3, b). Because the reaction of 1j in the presence of
1 equiv of chlorotriisopropylsilane afforded 2j as a sole
product and 2n, which could be obtained by the reaction
with TIPSCl, was not observed by NMR and GC-mass
spectroscopic analysis (eq 3), the possibility that the chlorine
atom mediated crossover of the silyl group was ruled out.8
Presumably, the much lower migration ability of the silyl
group compared to that of the carbon migrating groups led
to a longer lifetime for the silylsulfonium intermediate 4,
resulting in crossover of the silyl groups between two kinds
of reactive intermediate 4 in situ.
contrary, the reaction of 1p bearing a fluorine atom at R4
gave 2p in a good yield (88%), suggesting that a decrease
in nucleophilicity of the sulfur atom by the fluorine atom at
the meta-position of the silylthio group did not significantly
affect the cyclization step.
In conclusion, we are now in a position for synthesizing
3-silylbenzo[b]thiophenes in good to excellent yields. It
should be noted that the present reaction proceeds through
trans sulfur-silicon bond addition, so-called thiosilylation.10
The present reaction proceeded under mild conditions without
the formation of undesired byproducts, making this meth-
odology useful for the synthesis of highly functionalized
3-silylbenzo[b]thiophenes in an environmentally benign
manner.
Acknowledgment. This work was financially supported
by a Grant-in-Aid for Scientific Research from the Japan
Society for Promotion in Science (JSPS).
To study the electronic effect on both the alkynyl moiety
and the silylthio group, we carried out the reaction of fluoro-
substituted substrates 1o and 1p (eq 4). The reaction of 1o
having a fluorine atom at R3 afforded 2o in a lower yield
(51%), indicating that a decrease in electron density of the
triple bond by the electron-withdrawing fluorine atom at the
meta-position of the alkynyl moiety interferes with π-coor-
dination to the gold catalyst, thus diminishing the reactivity
for the cyclization.9 This result corresponds with that of 1h
having a 4-(trifluoromethyl)phenyl group at R1 giving the
Supporting Information Available: Experimental pro-
cedures and characterization of the products 2 and 6b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL701951N
(8) Heydari, A.; Alijanianzadeh, R. Chem. Lett. 2003, 226.
(9) Asao, N.; Asano, T.; Ohishi, T.; Yamamoto, Y. J. Am. Chem. Soc.
2000, 122, 4817.
(7) Yoshikawa, E.; Gevorgyan, V.; Asao, N.; Yamamoto, Y. J. Am.
Chem. Soc. 1997, 119, 6781.
(10) Platinum-catalyzed thiosilylation proceeds in a cis fashion. Han,
L.-B.; Tanaka, M. J. Am. Chem. Soc. 1998, 120, 8249.
Org. Lett., Vol. 9, No. 20, 2007
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