Palladium-catalyzed hydrophenylation of alkynes with sodium tetraphenylborate under mild conditions

Article abstract of DOI:10.1021/jo7020554

(Chemical Equation Presented) In an aqueous solution of acetic acid, PdCl₂(PPh₃)₂ showed high catalytic activity for the hydrophenylation of both terminal and internal alkynes with sodium tetraphenylborate (NaBPh₄) under mild conditions, affording phenyl alkenes in moderate to excellent yields.

Full text of DOI:10.1021/jo7020554

Palladium-Catalyzed Hydrophenylation of Alkynes with Sodium
Tetraphenylborate under Mild Conditions
Hanxiang Zeng and Ruimao Hua*
Department of Chemistry, Tsinghua UniVersity, InnoVatiVe Catalysis Program, Key Laboratory of Organic
Optoelectronics and Molecular Engineering of Ministry of Education, Beijing 100084, China
ruimao@mail.tsinghua.edu.cn
ReceiVed September 19, 2007
In an aqueous solution of acetic acid, PdCl2(PPh3)2 showed high catalytic activity for the hydrophenylation
of both terminal and internal alkynes with sodium tetraphenylborate (NaBPh4) under mild conditions,
affording phenyl alkenes in moderate to excellent yields.
Introduction
been described,7 and the reaction has been extended to the
arylative cyclization of alkyne-tethered olefins and aldehydes.8
However, the reaction of hydroarylation with sodium tetraphe-
nylborate, which is a stable and inexpensive phenylating reagent,
has rarely been reported.9 In this paper, we wish to develop an
efficient palladium-catalyzed hydrophenylation of alkynes with
sodium tetraphenylborate under mild conditions.
Catalytic hydroarylation of multiple carbon-carbon bonds
is an important method for constructing complex molecules from
relatively simple precursors. Although transition metal complex1
or Lewis acid2 catalyzed hydroarylations by direct activation
of a C-H bond of arenes have been intensively studied, most
research so far has focused only on the electron-rich arenes,
and the control of regioselectivity is still difficult. The use of
organoheteroatom compounds has also been described in
hydroarylation with high selectivity, such as diphenylantimony
chloride3 and tetraphenyltin.4 In particular, arylboron drew a
lot of attention recently, due to its high functional group
compatibility, ready availability, and stability. Miyaura and co-
workers reported the first rhodium-catalyzed addition of aryl-
boronic acid to R,â-unsaturated ketones in 1997.5 After that,
great effort was made in this rhodium-catalyzed asymmetric 1,4-
addition by applying a variety of appropriate chiral ligands.6
The hydroarylation of alkynes with arylboronic acid has also
Results and Discussion
The reaction of 1-octyne (1a) with sodium tetraphenylborate
was first investigated to optimize reaction conditions, and a
variety of acids and palladium catalysts were examined (Table
1). When a mixture of 1a (0.5 mmol), NaBPh4 (0.5 mmol), and
PdCl2(PPh3)2 (0.005 mmol) was stirred at room temperature in
glacial acetic acid or H2O for 6 h (entries 1 and 2), only a small
(6) Selected examples: (a) Takaya, Y.; Ogasawara, M.; Hayashi, T. J.
Am. Chem. Soc. 1998, 120, 5579-5580. (b) Takaya, Y.; Ogasawara, M.;
Hayashi, T. Tetrahedron Lett. 1999, 40, 6957-6961. (c) Hayashi, T.; Senda,
T.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 1999, 121, 11591-11592.
(d) Senda, T.; Ogasawara, M.; Hayashi, T. J. Org. Chem. 2001, 66, 6852-
6856. (e) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem.
Soc. 2003, 125, 11508-11509. (f) Otomaru, Y.; Kina, A.; Shintani, R.;
Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673-1679. (g) Chen, F.-
X.; Kina, A.; Hayashi, T. Org. Lett. 2006, 8, 341-344.
(1) Selected examples: (a) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.;
Kitamura, T.; Fujiwara, Y. Science 2000, 287, 1992-1995. (b) Lim, Y.-
G.; Lee, K.-H.; Koo, B. T.; Kang, J.-B. Tetrahedron Lett. 2001, 42, 7609-
7612. (c) Tsukada, N.; Mitsuboshi, T.; Setoguchi, H.; Inoue, Y. J. Am. Chem.
Soc. 2003, 125, 12102-12103. (d) Karshtedt, D.; Bell, A. T.; Tilley, T. D.
Organometallics 2004, 23, 4169-4171.
(2) Selected examples: (a) Yamaguchi, M.; Kido, Y.; Hayashi, A.;
Hirama, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 1313-1315. (b)
Yonehara, F.; Kido, Y.; Yamaguchi, M. Chem. Commun. 2000, 1189-
1190. (c) Reetz, M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485-3496.
(3) Matoba, K.; Motofusa, S.-i.; Cho, C. S.; Ohe, K.; Uemura, S. J.
Organomet. Chem. 1999, 574, 3-10.
(4) Ohe, T.; Uemura, S. Tetrahedron Lett. 2002, 43, 1269-1271.
(5) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16,
4229-4231.
(7) (a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am.
Chem. Soc. 2001, 123, 9918-9919. (b) Shirakawa, E.; Takahashi, G.;
Tsuchimoto, T.; Kawakami, Y. Chem. Commun. 2001, 2688-2689.
(8) (a) Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi,
T. J. Am. Chem. Soc. 2004, 127, 54-55. (b) Shintani, R.; Tsurusaki, A.;
Okamoto, K.; Hayashi, T. Angew. Chem., Int. Ed. 2005, 44, 3909-3912.
(9) (a) Cho, C. S.; Uemura, S. J. Organomet. Chem. 1994, 465, 85-92.
(b) Cho, C. S.; Motofusa, S.-i.; Ohe, K.; Uemura, S. J. Org. Chem. 1995,
60, 883-888.
10.1021/jo7020554 CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/14/2007
558
J. Org. Chem. 2008, 73, 558-562

Pd-Catalyzed Hydrophenylation of Alkynes with NaBPh4
TABLE 1. Reaction of 1-Octyne (1a) with Sodium
Tetraphenylboratea
TABLE 2. PdCl2(PPh3)2-Catalyzed Reaction of Alkynes with
Sodium Tetraphenylboratea
yield
entry
catalyst (mol %)
acid (equiv to 1a) (%)b
2a:3ac
1d
2e
3
PdCl2(PPh3)2 (1.0)
PdCl2(PPh3)2 (1.0)
PdCl2(PPh3)2 (1.0)
PdCl2(PPh3)2 (1.0)
PdCl2(PPh3)2 (3.0)
PdCl2(PPh3)2 (3.0)
PdCl2(PPh3)2 (3.0)
HOAc
<5
<5
65
80
98
49
67
HOAc (1.0)
HOAc (2.0)
HOAc (2.0)
HOAc (2.0)
p-nitrobenzoic
acid (2.0)
94:6
95:5
93:7
96:4
96:4
4
5
6f
7
8g
9
PdCl2(PPh3)2 (3.0)
PdCl2(PCy3)2 (3.0)
Pd(OAc)2 (3.0)
PdCl2 (3.0)
PdCl2 (3.0) + PPh3 (6.0) HOAc (2.0)
Pd(PPh3)4 (3.0)
HCl(aq)
0
6
HOAc (2.0)
HOAc (2.0)
HOAc (2.0)
>99:1
>99:1
57:43
>99:1
97:3
10
11
12
13
14
15h
12
17
13
33
0
HOAc (2.0)
HOAc (2.0)
HOAc (2.0)
NiCl2(PPh3)2 (3.0)
NiCl2(dppp) (3.0)
7
>99:1
a Unless otherwise noted, reactions were carried out using 0.5 mmol of
1a and 0.5 mmol of NaBPh4 with acid and catalyst in 1.0 mL of H2O in a
sealed tube at room temperature for 6 h. b Total GC yield. c Determined
by GC. d In 1.0 mL of acetic acid. e In 1 mL of deionized water. f 0.5 equiv
of NaBPh4. g In 1.0 mL of 36% HCl. h dppp ) 1,3-bis(diphenylphophino)
propane.
amount of 2a was formed (confirmed by GC-MS). In an aqueous
solution of acetic acid (0.5 mmol), however, the reaction was
significantly improved to give the hydrophenylation product in
65% GC yield with perfect regioselectivity in favor of the
Markovnikov adduct 2a (entry 3). Increasing the amount of acid
or catalyst loading was found to further promote the reaction
(entries 3-5), and the highest yield of adducts was obtained
by the use of 3.0 mol % PdCl2(PPh3)2 and 2.0 equiv of acetic
acid (entry 5). Decreasing the amount of NaBPh4 to 0.5 equiv
resulted in lower yield of only 49% (entry 6), which means
that only one phenyl group was efficiently utilized under this
condition. Other acids were also tested in our study. The use of
p-nitrobenzoic acid gave somewhat lower yield (67%, entry 7),
whereas the catalyst completely lost its activity in concentrated
aqueous hydrocholoric acid and all of the starting materials were
recovered. This was possibly caused by the strong affinity of
chloride ion to the palladium. In addition, we employed other
palladium or nickel catalysts, but none of them displayed good
activity (entries 9-15). It should also be noted that the PPh3
ligand seems to have a great influence on the selectivity, since
the use of PdCl2 apparently did not favor the Markovnikov
adduct (entry 11) and the addition of PPh3 did not promote the
reaction but changed the selectivity (entry 12).
a Reactions were carried out using alkyne (1.0 mmol), NaBPh4 (1.0
mmol), HOAc (2.0 mmol), and PdCl2(PPh3)2 (0.03 mmol) in H2O (2.0 mL)
in a sealed tube at room temperature for 6 h. b Isolated yield. c Determined
by GC.
TABLE 3. Reaction of Diphenylacetylene (1h) with Sodium
Tetraphenylboratea
amount of NaBPh4
(equiv to 1h)
temp
(°C)
time
(h)
yield
(%)b
entry
1
2
3
4
0.33
0.33
0.33
0.25
rt
rt
50
50
6
24
12
12
58
71
96
75
a Reactions were carried out using 1h (1.0 mmol), NaBPh4 as indicated
in the table, HOAc (2.0 mmol), and PdCl2(PPh3)2 (0.03 mmol) in H2O (2.0
mL in a sealed tube. b Isolated yield based on 1h used.
In order to assess the scope of this process, we have examined
the hydrophenylation of several terminal and internal alkynes
under the optimized condition indicated in entry 5 of Table 1.
The results are summarized in Table 2. As expected, 1-heptyne
(1b) showed similar reactivity as 1a to furnish 2b in 87% yield
(entry 1). However, in the cases of phenylacetylene (1c) and
5-chloropent-1-yne (1d), the corresponding adducts 2c and 2d
were isolated in somewhat low yields (entries 2 and 3). It should
be noted that the C-Cl bond of 1d was intact.
and 1g reacted with NaBPh4 to afford the trisubstituted alkenes
2e, 2f, and 2g in good to high yields (entries 4-6), and the
hydrophenylation of diphenylacetylene (1h) afforded the cor-
responding adduct 2h in quantitative yield (entry 7). Further-
more, the reaction of electron-deficient internal alkyne 1i gave
the adduct 2i in 81% yield (entry 8). As for the unsymmetrical
internal alkynes, the regioselectivity depends on the nature of
substitutents. In the case of 1-phenylpropyne (1j), the two cis-
adducts 2j and 3j were isolated in 44% and 31% yields,
respectively (entry 9). However, the use of methyl but-2-ynoate
(1k) resulted in the formation of methyl 3-phenyl-2-butenoate
Under the same reaction conditions, the hydrophenylation of
internal alkynes also took place smoothly at room temperature
to give cis-adducts. For example, dialkylated acetylene 1e, 1f,
J. Org. Chem, Vol. 73, No. 2, 2008 559

Zeng and Hua
SCHEME 1. Proposed Mechanism for
Palladium(II)-Catalyzed Hydrophenylation of Alkynes with
NaBPh4
(2k) in excellent yield and regioselectivity, indicating that the
phenyl group was almost exclusively introduced at the position
â to the ester group (entry 10).
Although the reaction of 2-methylbut-3-yn-2-ol (1l) with
sodium tetraphenylborate at room temperature afforded a
complicated mixture, in which the formation of corresponding
adduct could be determined by GC and GC-MS, when the same
reaction was performed at 50 °C for 12 h, interestingly, (E)-2-
methyl-4-phenyl-buta-1,3-diene (4) was obtained in 75% isolated
yield (eq 1). These results indicated that, in contrast to linear
terminal alkynes, the use of sterically congested 1l resulted in
selective formation of the anti-Markovnikov adduct, which
underwent dehydration to give 4 under the reaction conditions.
Since many alkynols are relatively easy to access, this process
could be used as a practical method for the synthesis of
conjugated dienes.
TABLE 4. Palladium-Catalyzed Reactions of Alkynes with Sodium
Tetraphenylboratea
However, when 2-phenylbut-3-yn-2-ol (1m) was employed,
no expected products of dehydration could be obtained, and the
corresponding Markovnikov adduct 2m and trans anti-Mark-
ovnikov adduct 3m were isolated in low yields (eq 2). Likewise,
as a result of the steric hindrance of substituents, the formation
of the anti-Markovnikov adduct was favored.
The hydrophenylations of 1,3-diynes were also examined, and
the reactions took place smoothly under the same conditions.
The conversion of 1,4-bis(trimethylsilyl)buta-1,3-diyne (5a) was
almost quantitative, affording both singly and doubly phenylated
products 6 and 7 in 85% and 13% yields, respectively (eq 3).
In the case of 1,4-diphenylbuta-1,3-diyne (5b), the reaction gave
three doubly phenylated products that were isolated in 85% as
a mixture (eq 4). Attempts to separate these adducts were not
successful, and only 8 was isolated in analytical purity with
low yield (15%).
a Reactions were carried out using alkyne (1.0 mmol), NaBPh4 (0.3
mmol), HOAc (2.0 mmol), and PdCl2(PPh3)2 (0.03 mmol) in H2O (2.0 mL)
in a sealed tube at 50 °C for 12 h. b Isolated yield based on alkyne used.
1
c Determined by GC. d Determined by H NMR.
In previous reports on the hydrophenylation of alkenes with
NaBPh49 and coupling reaction of NaBPh4 with aryl halides,10
usually only one or two phenyl groups could be transferred. As
shown in Table 2, entry 7, the reaction of diphenylacetylene
(1h) with NaBPh4 afforded the adduct 2h in quantitative yield.
In order to explore the possibility for further efficient transfer
of phenyl groups in NaBPh4, we examined the reaction of 1h
with 0.33 or 0.25 equiv of NaBPh4 again under different
conditions. As summarized in Table 3, either increasing reaction
temperature or prolonging reaction time could promote the
reaction, and a satisfactory result could be achieved when the
reaction was performed at 50 °C for 12 h with 0.33 equiv of
NaBPh4, indicating that at most three phenyl groups could be
efficiently utilized (entries 3 and 4).
To demonstrate the generality and efficiency of the above
process, we carried out the reaction of 0.33 equiv of NaBPh4
with several other alkynes at 50 °C (Table 4). Although the
reaction of 1a with 0.33 equiv of NaBPh4 afforded adducts in
51% yield (entry 1), similar to the result by using 0.5 equiv of
(10) Wang, J.-X.; Yang, Y.; Wei, B. Synth. Commun. 2004, 34, 2063-
2069.
560 J. Org. Chem., Vol. 73, No. 2, 2008

Pd-Catalyzed Hydrophenylation of Alkynes with NaBPh4
NaBPh4 at room temperature as indicated in entry 6 of Table
1, the internal alkynes underwent the hydrophenylation smoothly
to give corresponding products in good to high yields (entries
2-4). Both yields of adducts and the selectivities of reactions
are comparable to the results summarized in Table 2.
It is known that NaBPh4 can react with acetic acid to give
Ph3B, benzene, and sodium acetate, and Ph3B can be further
hydrolyzed into di- and monophenylboronic acid.9 Therefore,
we also examined the reactivity of Ph3B and PhB(OH)2 with
alkyne at room temperature. As shown in eqs 5 and 6, the
reactions of 1h with Ph3B or PhB(OH)2 also afforded 2h in
moderate yields.
a similar reaction as eq 8 gave the product with deuterium
incorporated at the ortho position of the phenyl group, which
was caused by 1,4-rearrangement of rhodium in intermediate
C.7a Larock has also reported similar behavior in the Pd-
catalyzed reaction of alkynes and aryl iodide.14 However,
possibly as a result of milder reaction conditions, no migration
was observed in the present catalysis system.
On the basis of the above observations, we proposed a
possible mechanism for the present hydrophenylation in Scheme
1. It includes the oxidative addition of the C-B bond to Pd(0)
species to give intermediate B11 and selective insertion of alkyne
into Pd-C to give C. Hydrolysis of C followed by reductive
elimination of the C-C bond finally gives the hydrophenylating
products and regenerates the Pd(0) species. Ph3B, Ph2B(OH),
and PhB(OH)2 should be the possible phenylating intermediates
in the reaction system.
The results obtained in this work can be rationally explained
by this proposed mechanism: (1) the formation of benzene was
found in all the reactions confirmed by GC and GC-MS, and
thus only three phenyl groups in NaBPh4 could be maximally
efficiently used; (2) the dominant formation of Markovnikov-
type adduct in the hydrophenylation of terminal alkynes is due
to the selective insertion of a terminal alkyne (R ) H) into
Pd-C bonds with the R′ group away from the metal center to
give the less steric repulsion intermediate C; (3) the regiose-
lectivity of the phenyl group attached to the position â to the
ester group in the reactions of propiolates 1k, 1n, and 1o (R )
COOR′′) is possibly resulted from the interaction of palladium
and ester group.12
In addition, the careful analyses of the reaction mixture
indicated in entry 5 of Table 1 disclosed the formation of mono-
and diphenylboronic acids, and we have also successfully
isolated PhB(OH)2 from the reaction mixture and found that
PhB(OH)2 is in equilibrium with triphenylboroxin in CDCl3 (eq
7).13 Moreover, as shown in eq 8, the reaction of 1a in D2O
afforded selectively deuterated product 2a-d, which again
confirmed the cis-type addition manner. These findings gave
direct evidence to support our proposed mechanism. More
interestingly, in Hayashi’s Rh-catalyzed hydroarylation system,
Conclusions
In summary, we have developed a palladium-catalyzed
hydrophenylation of alkynes with sodium tetraphenylborate with
improved utilization efficiency of the reagent. From a synthetic
point of view, the present catalytic procedure to produce
arylalkenes has advantages over other methods in that it took
place in an aqueous solution under mild conditions with high
regio- and stereoselectivity and several functional groups were
tolerated.
Experimental Section
Typical Procedure for Hydrophenylation of 1-Octyne (1a)
with Sodium Tetraphenylborate To Afford 2-Phenyloct-1-ene15
(2a) (Table 1, entry 5). A mixture of 1-octyne (1a) (74.0 µL, 0.5
mmol), NaBPh4 (171.1 mg, 0.5 mmol), HOAc (58.0 µL, 1.0 mmol),
PdCl2(PPh3)2 (10.5 mg, 0.015 mmol), and H2O (1.0 mL) was stirred
under nitrogen in a sealed tube at room temperature for 6 h. After
reaction, the mixture was first subjected to a short silica column
chromatography (ca. 5 cm of silica gel, eluted with CH2Cl2) to
remove the water. Then octadecane (92.5 mg, 0.36 mmol) was
added in the elution as internal standard for GC analysis. After
GC and GC-MS analysis, the solvents and volatiles were removed
under vacuum, and the residue was then subjected to preparative
TLC isolation (silica, eluted with petroleum ether). Compound 2a
was obtained in 84.7 mg (0.45 mmol, 90%) as a yellow oil. The
result of GC analysis of the reaction mixture revealed that 2a and
3a were formed in a total of 98% yield with a ratio of 93:7. Data
for 2a: 1H NMR (300 MHz, CDCl3) δ 7.39-7.21 (m, 5H), 5.24
(d, 1H, J ) 1.5 Hz), 5.03 (d, 1H, J ) 1.5 Hz), 2.48 (t, 2H, J ) 7.4
Hz), 1.48-1.23 (m, 8H), 0.86 (t, 3H, J ) 6.9 Hz); 13C NMR (75
MHz, CDCl3) δ 148.8, 141.5, 128.2, 127.2, 126.1, 112.0, 35.4, 31.7,
29.1, 28.3, 22.7, 14.1; GC-MS m/z 188 (M+).
Hydrophenylation of Diphenylacetylene (1h) with Sodium
Tetraphenylborate To Afford Triphenylethene (2h)16 at El-
evated Temperature (Table 3, entry 3). A mixture of diphenyl-
(11) Oxidative addition of a carbon-boron bond to Pd(0) has so far been
proposed in several cases: (a) Ohe, T.; Ohe, K.; Uemura, S.; Sugita, N. J.
Organomet. Chem. 1988, 344, C5. (b) Cho, C. S.; Uemura, S. J. Organomet.
Chem. 1994, 465, 85-92. (c) Cho, C. S.; Motofusa, S.-i.; Ohe, K.; Uemura,
S. J. Org. Chem. 1995, 60, 883-888.
(12) The interaction of carbonyl group and transition metal complex has
been previously reported in catalyzed 1,4-additions. See refs 5 and 8.
(13) For review, see: Lappert, M. F. Chem. ReV. 1956, 56, 959-1064.
(14) Tian, Q.; Larock, C. L. Org. Lett. 2000, 2, 3329-3332.
(15) Yoshida, K.; Hayashi, T. J. Am. Chem. Soc. 2003, 125, 2872-2873.
(16) Song, C. E.; Jung, D.-u.; Choung, S. Y.; Roh, E. J.; Lee, S.-g.;
Angew. Chem., Int. Ed. 2004, 43, 6183-6185.
J. Org. Chem, Vol. 73, No. 2, 2008 561

Zeng and Hua
acetylene (1h) (178.2 mg, 1.0 mmol), NaBPh4 (112.9 mg, 0.33
mmol), HOAc (116.0 µL, 2.0 mmol), PdCl2(PPh3)2 (21.0 mg, 0.03
mmol), and H2O (2.0 mL) was heated in a sealed tube under
nitrogen at 50 °C for 12 h. After reaction, the mixture was first
subjected to a short silica column chromatography (ca. 5 cm of
silica gel, eluted with CH2Cl2) to remove the water. The elution
was condensed and subjected to GC and GC-MS analysis. After
that, the solvents and volatiles were removed under vacuum, and
the residue was then subjected to preparative TLC isolation (silica,
eluted with petroleum ether). Compound 2h was obtained in 245.9
mg (0.96 mmol, 96%) as a pale yellow oil. Data for 2h: 1H NMR
(300 MHz, CDCl3) δ 7.33-6.95 (m, 16H); 13C NMR (75 MHz,
CDCl3) δ 143.4, 142.5, 140.3, 137.3, 130.3, 129.5, 128.6, 128.2,
128.1, 127.9, 127.6, 127.5, 127.4, 126.7; GC-MS m/z 256 (M+).
Acknowledgment. This project (20573061) was supported
by National Natural Science Foundation of China.
Supporting Information Available: General method, charac-
terization data and charts of 1H and 13C NMR for all products. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO7020554
562 J. Org. Chem., Vol. 73, No. 2, 2008