Rhodium-copper-TBAF-catalyzed hydroarylation of alkynes with aryl Trimethoxysilanes

Article abstract of DOI:10.1016/j.tetlet.2009.01.130

A rhodium-copper-TBAF-catalyzed hydroarylation of alkynes with aryl trimethoxysilanes is described. The procedure utilizes a catalytic amount of copper(II) acetate, rhodium, PPh₃ and TBAF·3H₂O under air. Some asymmetric alkynes gave

Full text of DOI:10.1016/j.tetlet.2009.01.130

Tetrahedron Letters 50 (2009) 1714–1716
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Rhodium–copper–TBAF-catalyzed hydroarylation of alkynes with aryl
Trimethoxysilanes
*
Baoda Lin, Miaochang Liu, Zhishi Ye, Qin Zhang, Jiang Cheng
College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A rhodium–copper–TBAF-catalyzed hydroarylation of alkynes with aryl trimethoxysilanes is described.
The procedure utilizes a catalytic amount of copper(II) acetate, rhodium, PPh3 and TBAFꢀ3H2O under
air. Some asymmetric alkynes gave the products with high regioselectivities.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 5 November 2008
Revised 21 January 2009
Accepted 24 January 2009
Available online 30 January 2009
The regio- and stereoselective synthesis of multi-substituted
olefins has been a challenge for synthetic organic chemists for
years.1 Recently, much attention has been paid to rhodium-cata-
lyzed hydroarylation of alkynes to access the aforementioned com-
pounds.2 Such hydroarylation and hydroalkenylation have already
been attained by palladium- or nickel-catalyzed addition of orga-
nometallic compounds to the alkynes, or by titanium-catalyzed
hydrozincation of alkynes.3 Very recently, the transition-metal-
catalyzed addition of arylboronic acids to unsaturated C–C bonds
to achieve these analogues has drawn considerable attention due
to the advantages of organoboron reagents.4 However, either a
coordinate or electron-withdrawing group was required in the re-
ported addition of boronic acids to asymmetrical alkynes. Com-
pared with the organoborons, organosilane reagents, especially
aryl triethoxysilanes, are of lower cost5 and easier to be purified
by distillation or chromatography.6 However, examples of employ-
ing organosilanes in this transformation were scarely reported or
had limited substrates scope.7 Herein, we wish to report rho-
dium–copper–TBAF-catalyzed hydroarylation of symmetrical and
asymmetrical alkynes with aryl trimethoxysilanes, providing the
tri-substituted alkenes in moderate to good yields (Fig. 1).
Recently, we have developed a copper-catalyzed arylation of
amines and amides employing aryl trimethoxysilanes, which were
activated by catalytic amounts of TBAF.8 We have also reported a
phosphine-free rhodium-catalyzed hydroarylation of alkynes with
boronic acids (Scheme 1).9 Our interests in the development of
transition-metal-catalyzed additions of arylmetallic reagents to
the carbon–carbon or carbon–hetero unsaturated bonds10 spur us
to explore the possibility of using organosilanes activated by cata-
lytic amounts of fluoride salts in such transformation.
Initial studies were conducted using the addition of phenyl tri-
methoxysilane 1a to diphenyl acetylene 2a as a model reaction.
Unfortunately, the combination of PPh3, Cu(OAc)2 and a series of
rhodium sources almost did not deliver the desired product (Table
1, entries 1–4). After intensive screening, we found that the prod-
uct 3aa was formed in 92% yield by employing Rh(cod)Cl dimer as
rhodium source with the combination of PPh3 and Cu(OAc)2.
Chloro bis(cyclooctene) rhodium(I) also gave the product in almost
the same yield (Table 1, entry 5). Encouraged by this promising re-
sult, we tested other parameters, such as ligands and copper
sources. Other copper salts were inferior to Cu(OAc)2. The ligand
also played an important role in the reaction. Among the phos-
phine ligands tested, monodent and bident and the ones bearing
electron-rich or -deficient aryl groups all showed moderate activity
in the reaction (Table 1, entries 12–18). However, the common and
4-tol 4-tol
+
Rh, Cu, PPh3
TBAF.3H2O
toluene/H2O
+
Si(OMe)3 Ph
R
Ph
R
Ph
R
3'
2
1b
3
4-tol
4-tol
Bu
2-Py
Ph
Ph
Ar'
Ar
Rh(CO)2(acac)
toluene/H2O
3bj 70% (88:12)
3bk 88% (95:5)
Ar'B(OH)2
+
Ar
Ar
Ar
Figure 1. Hydroarylation of asymmetric alkynes. (Isolated yield with regioselective
(3:30 in parentheses), which were determined by 1H NMR.)
Cu(OAc)2, TBAF.3H2O
P(C6F5)3,O2, 4 Å MS
R2
R1
+
ArSi(OMe)3
Ar
N
NH
R1
R2
* Corresponding author. Tel./fax: +86 577 88156826.
E-mail address: jiangcheng@wzu.edu.cn (J. Cheng).
Scheme 1. Our previous work.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.130

B. Lin et al. / Tetrahedron Letters 50 (2009) 1714–1716
1715
Table 1
and 8). It is noteworthy that 3ah is difficult to be prepared from
corresponding organoboron in Hayashi’s procedure since a 1,4-
rhodium shift occurs in the catalytic cycle.4c However, in our pro-
cedure, 1a reacted smoothly with 2h, and produced the product
3ah in 73% isolated yield (Table 2, entry 8). The presence of elec-
tron-donating substituents on the phenyl ring decreased the yields.
Notably, the dialkyl acetylene, 3-hexyne 2j was also a good reac-
tion partner under the conditions (Table 2, entry 10), albeit 3aj
was isolated in moderate yield.
Next, we turned our attention to broaden the scope of aryl tri-
methoxysilanes. A series of ArSi(OMe)3 were tested in the reaction
condition and all delivered the product in moderate to good yields.
The hindrance on the aryl group of ArSi(OMe)3 had little effect on
the reaction. For example, 3ca and 3fa were isolated in 91% and
73% yields, respectively (Table 3, entries 2 and 5). However, the
feasibility of access to highly hindered triaryl ethene by using
2,6-di-MeC6H3Si(OMe)3 and diphenyl acetylene failed (Table 3, en-
try 4).
Having demonstrated the utility of an addition reaction condi-
tion on a number of symmetrical diaryl alkynes, we chose to test
the generality of the addition to asymmetrical internal alkynes.
Employing 2-(2-phenylethynyl)pyridine 2m as the substrate, the
product 3bj was delivered in 70% yield with 88:12 regioselectivity.
The pyridin-2-yl attached in the triplet C–C bonds may coordinate
with rhodium to increase the regioselectivity.11 It is noteworthy
that high regioselectivity was obtained when aryl alkyl acetylene
was used as substrate. For example, 3bk was isolated in 88% yield
with 95:5 regioselectivity. To the best our knowledge, the asym-
metrical addition of arylboronic acids to aryl alkyl acetylene were
rarely studied before.4c As such, this represents an exceedingly
practical method for the synthesis of tri-aryl-substituted olefins,
and offers an attractive alternative to traditional organoboron
addition procedures.
Screening for the optimum conditionsa
Ph
Ph
Ph
Cu, Rh, ligand, TBAF.3H2O
toluene/H2O, 110 ºC, air
+
PhSi(OMe)3
2a
1a
3aa
Entry
Rh source
Cu source
Ligand
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Rh(cod)(acac)
Rh(CO)2(acac)
RhCl3ꢀ3H2O
Rh(PPh3)3Cl
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
[Rh(cod)Cl]2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuSO4
CuBr2
CuF2
Cu(OTf)2
CuCl2
CuI
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
<5
<5
<5
<5
92 (91)c
16
<5
26
15
35
52
<5
23
25
28
37
57
<5
PPh3
PPh3
PPh3
P(2-MeC6H4)3
P(3,5-di-MeC6H3)3
P(4-MeOC6H4)3
dppe
P(C6F5)3
P(1-naph)3
P(4-ClC6H4)3
PPh3
<5
a
All reactions were run with phenyl trimethoxysilane (59.4 mg, 0.3 mmol),
diphenyl acetylene (36 mg, 0.2 mmol), Cu source (10 mol %), TBAFꢀ3H2O (6.3 mg,
10 mol %), ligand (10 mol %), Rh source (10 mol %) and solvent (3.05 mL, toluene/
H2O = 60:1) under air at 110 °C for 24 h.
b
Isolated yield.
Chlorobis(cyclooctene) rhodium(I) as rhodium source.
c
commercial available PPh3 was the best. The presence of a proper
portion of H2O is crucial to the reaction. The reaction did not pro-
ceed in dry toluene, and excess H2O decreased the yield. Higher
yield was obtained when the reaction was carried out under air in-
stead of under nitrogen. Thus, the rigorous exclusion of air/mois-
ture is not required in this transformation.
Table 3
a
Hydroarylation of diphenyl acetylene with ArSi(OMe)3
With the optimized reaction conditions in hand, we then ex-
plored the scope of alkynes, as shown in Table 2.
As expected, all the reactions proceeded smoothly and provided
the desired products in moderate to good yields. The hindrance of
the alkynes had some effect on the reaction, for example, 66% and
73% of 3ab and 3ah were isolated, respectively (Table 2, entries 2
Ar
Rh, Cu, PPh3
TBAF.3H2O
toluene/H2O
ArSi(OMe)3
+
Ph
Ph
Ph
Ph
2a
3
1
Entry
Ar
Product
Yielda,b (%)
1
2
3
4
5
6
7
8
9
4-MeC6H4– 1b
2-MeC6H4– 1c
3-MeC6H4– 1d
2,6-Di-MeC6H3– 1e
2-MeOC6H4– 1f
3ba
3ca
3da
3ea
3fa
3ga
3 ha
3ia
80
91
63
<5
73
63
50
57
82
Table 2
a
Hydroarylation of alkynes with PhSi(OMe)3
Ph
4-MeOC6H4– 1g
Rh, Cu, PPh3
TBAF.3H2O
toluene/H2O
PhSi(OMe)3
+
R
R
1-Naphthalenyl 1h
2-Naphthalenyl 1i
3,5-Di-MeC6H3- 1j
R
R
3ja
3
1a
2
a
Reaction conditions: ArSi(OMe)3 (0.3 mmol), diphenyl acetylene (36 mg,
0.2 mmol), Cu(OAc)2 (3.6 mg, 10 mol %), TBAFꢀ3H2O (6.3 mg, 10 mol %), PPh3
(5.2 mg, 10 mol %), [Rh(cod)Cl]2 (4.9 mg, 5 mol %) and toluene/H2O (3.05 mL, 60:1)
under air at 110 oC for 12 h.
Entry
R
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
Ph 2a
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
90
66
71
80
57
76
87
73
90
2-MeC6H4– 2b
3-MeC6H4– 2c
4-MeC6H4– 2d
4-MeOC6H4– 2e
1-Naphthalenyl 2f
2-Naphthalenyl 2 g
2,6-Di-Me–C6H3– 2 h
3,5-Di-Me–C6H3– 2i
b
Isolated yield.
Rh, Cu, PPh3
TBAF.3H2O
toluene/D2O
PhSi(OMe)3
+
a
Reaction conditions: PhSi(OMe)3 (59 mg, 0.3 mmol), diaryl acetylene
(0.2 mmol), Cu(OAc)2 (3.6 mg, 10 mol %), TBAFꢀ3H2O (6.3 mg, 10 mol %), PPh3
(5.2 mg, 10 mol %), [Rh(cod)Cl]2 (4.9 mg, 5 mol %) and toluene/H2O (3.05 mL, 60:1)
under air at 110 oC for 12 h.
D
Ph
3aa', yield: 62%
1a
2a
Scheme 2. Labeling study.
b
Isolated yield.

1716
B. Lin et al. / Tetrahedron Letters 50 (2009) 1714–1716
RhLnCl
H2O
Acknowledgments
ArSi(OMe)3
1
We thank the National Natural Science Foundation of China
(No. 20504023) and Natural Science Foundation of Zhejiang Prov-
ince for Distinguished Young Students (No. 2007R40G2250037)
for financial support.
H2O, TBAF
[ArSi(OH)3F]-
RhLn(OH)
A
Ph
Ar
Ph
H
transmetallation
3
References and notes
hydrolysis
1. (a) Denmark, S. E.; Amburgey, J. J. Am. Chem. Soc. 1993, 115, 10386; (b) Creton,
I.; Marek, I.; Normant, J. F. Synthesis 1996, 1499; (c) Brown, S. D.; Armstrong, R.
W. J. Am. Chem. Soc. 1996, 118, 6331; (d) Organ, M. G.; Cooper, J. T.; Rogers, L. R.;
Soleymanzadeh, F.; Paul, T. J. Org. Chem. 2000, 65, 7959.
H2O
2. Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169.
Ph
Ar
Ph
Ar-RhLn
B
3. (a) Suzuki, A. Acc. Chem. Res. 1982, 15, 178; (b) Miyaura, N.; Suzuki, A. Chem.
Rev. 1995, 95, 2457; (c) Suzuki, A. J. Organomet. Chem. 1999, 576, 147; (d)
Darses, S.; Genet, J. P. Eur. J. Org. Chem. 2003, 4313.
RhLn
C
4. For Pd-catalyzed reactions, see: (a) Oh, C. H.; Jung, H. H.; Kim, K. S. Angew.
Chem., Int. Ed. 2003, 42, 805; (b) Oh, C. H.; Ahn, T. W.; Reddy, V. R. Chem.
Commun. 2003, 2622; For Rh-catalyzed reactions, see: (c) Hayashi, T.; Inoue, K.;
Taniguchi, N.; Ogasawara, M. J. Am. Chem. Soc. 2001, 123, 9918; (d) Oguma, K.;
Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem. Soc. 2000, 122, 10464; (e) Lautens,
M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Martin-Matute, B. J. Am. Chem. Soc. 2001,
123, 5358; (f) Boiteau, J.; Imbos, R.; Minnaard, A. J.; Feringa, B. L. Org. Lett. 2003,
5, 681; For Ni-catalyzed reactions, see: (g) Shirakawa, E.; Takahashi, G.;
Tsuchimoto, T.; Kawakami, Y. Chem. Commun. 2001, 2688; (h) Houpis, I. N.; Lee,
J. Tetrahedron 2000, 56, 817; For review on the organozinc reagents, see: (i)
Knochel, P.; Almena Perea, J. J.; Jones, P. Tetrahedron 1998, 54, 8275.
5. Mitchell, T. N.. In Metal-Catalyzed Cross-Coupling Reactions; de Mejijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 1, pp 125–162.
6. Manoso, A. S.; Ahn, C.; Soheili, A.; Handy, C. J.; Correia, R.; Seganish, W. M.;
DeShong, P. J. Org. Chem. 2004, 69, 8305.
insertion
Ph
Ph
2
Scheme 3. Plausible mechanism.
Labelling studies were conducted, and the result clearly showed
that the H attached to the C'C bond derived from the solvent
(Scheme 2). Moreover, the fact that product 3ah was formed in
73% also ruled out the possibility of 1,4-rhodium shift.4c
A plausible mechanism is outlined in Scheme 3. The water may
play three roles in this transformation: (1) promote the hydrolysis
of the aryl trialkoxysilane to the corresponding aryl silanol, which
is considered to be the actual reagent;12 (2) hydrolyze the rhodium
precatalyst into RhLn (OH) and (3) hydrolyze the rhodium species
formed via the insertion of aryl rhodium species into the triplet
bond, and regenerate the rhodium catalyst. However, the detailed
mechanism, especially the catalytic cycle of the fluoride and the
role of Cu(OAc)2, is still unclear.
In conclusion, we have developed an efficient and versatile rho-
dium-catalyzed addition of ArSi(OMe)3 to alkynes, providing the
hydroarylation products in moderate to good yields. The wide
range of substrates, the high regioselectivities for some asymmet-
ric alkynes, as well as the utilization of the catalytic amount of
TBAF as additive all together are the most attracting characteristics
of this reaction. Furthermore, the rigorous exclusion of air/mois-
ture is not required in these transformations. Mechanistic investi-
gations and the application of the ArSi(OMe)3 activated by catalytic
amount of TBAF to other unsaturated bonds are now in progress.13
7. Fujii, T.; Koike, T.; Mori, A.; Osakada, K. Synlett 2002, 295.
8. Lin, B.; Liu, M.; Ye, Z.; Ding, J.; Wu, H; Cheng, J. Org. Biomol. Chem. 2009.
doi:10.1039/b819510b.
9. Zhang, W.; Liu, M.; Wu, H.; Ding, J.; Cheng, J. Tetrahedron Lett. 2008, 49, 5214.
10. (a) Qin, C.; Wu, H.; Cheng, J.; Chen, X.; Liu, M.; Zhang, W.; Su, W.; Ding, J. J. Org.
Chem. 2007, 72, 4102; (b) Qin, C.; Chen, J.; Wu, H.; Cheng, J.; Zhang, Q.; Zuo, B.;
Su, W.; Ding, J. Tetrahedron Lett. 2008, 49, 1884; (c) Zhang, Q.; Chen, J.; Liu, M.;
Wu, H.; Cheng, J.; Qin, C.; Su, W.; Ding, J. Synlett 2008, 935.
11. The rhodium-catalyzed regioselective hydroarylation reaction of 2-(2-
phenylethynyl)pyridine with arylboronic acids, see: (a) Lautens, M.; Yoshida,
M. Org. Lett. 2002, 4, 123; (b) Lautens, M.; Yoshida, M. J. Org. Chem. 2003, 68,
762.
12. Organosilanols have been reported to be reactive towards transmetallation
with palladium, see: Oi, S.; Honma, Y.; Inoue, Y. Org. Lett. 2002, 4, 667.
13. General procedure: A reaction tube was charged with ArSi(OMe)3 (0.3 mmol),
Cu(OAc)2 (3.6 mg, 10 mol %), TBAFꢀ3H2O (6.3 mg, 10 mol %), PPh3 (5.2 mg,
10 mol %), [Rh(cod)Cl]2 (4.9 mg, 5 mol %), toluene (3 mL) and alkynes
(0.2 mmol) under atmosphere at room temperature. After stirring for 2 h,
60 lL of water was added, and the reaction mixture was continued to be
stirred under atmosphere at reflux for 12 h. After the completion of the
reaction, as monitored by TLC, the solvent was evaporated under reduced
pressure and the residue was purified by flash column chromatography on a
silica gel to give the product.