Palladium-catalyzed decarboxylative coupling of alkynyl carboxylic acids with benzyl halides or aryl halides

Article abstract of DOI:10.1021/jo1010284

(Figure presented) The synthesis of internal benzyl alkynes and 1,2-diarylalkynes has been developed via palladium-catalyzed decarboxylative coupling reactions of alkynyl carboxylic acids with benzyl chlorides or aryl halides. In the presence of Pd(OAc)₂ and Xphos (L3), alkynyl carboxylic acids smoothly underwent the reaction with various benzyl halides, providing the corresponding benzyl alkynes in moderate to good yields. It is noteworthy that the optimal conditions are compatible with a wide range of aryl halides including less active aryl chlorides.

Full text of DOI:10.1021/jo1010284

pubs.acs.org/joc
Palladium-Catalyzed Decarboxylative Coupling of Alkynyl Carboxylic
Acids with Benzyl Halides or Aryl Halides
Wen-Wu Zhang,† Xing-Guo Zhang,† and Jin-Heng Li*,†,‡
†College of Chemistry and Materials Science, Wenzhou University, Wenzhou 325035, China, and
‡Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education),
Hunan Normal University, Changsha 410081, China
jhli@hunnu.edu.cn
Received May 26, 2010
The synthesis of internal benzyl alkynes and 1,2-diarylalkynes has been developed via palladium-
catalyzed decarboxylative coupling reactions of alkynyl carboxylic acids with benzyl chlorides or aryl
halides. In the presence of Pd(OAc)2 and Xphos (L3), alkynyl carboxylic acids smoothly underwent
the reaction with various benzyl halides, providing the corresponding benzyl alkynes in moderate to
good yields. It is noteworthy that the optimal conditions are compatible with a wide range of aryl
halides including less active aryl chlorides.
Introduction
partners, are commercially available and inexpensive. These
methodologies commonly involve the decarboxylative Heck
coupling,1 aldol additions,2 decarboxylative enolate alkyla-
tion,3 and decarboxylative cross-coupling reactions.4-8
Although the decarboxylative coupling reaction with alkynyl
carboxylic acid substrates has been rarely explored,6 these
transformations are interesting by comparison with the
In the past decade transition metal-catalyzed decarboxy-
lative coupling reactions have emerged as useful tools for
constructing the carbon-carbon bonds in organic synthesis
because acids and their derivatives, one of the reaction
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Gooβen, L. J.; Paetzold, J. Angew. Chem., Int. Ed. 2004, 43, 1095. (d) Zhang,
S.-L.; Fu, Y.; Shang, R.; Guo, Q.-X.; Liu, L. J. Am. Chem. Soc. 2010, 132,
638.
(2) (a) Nokami, J.; Mandai, T.; Watanabe, H.; Ohyama, H.; Tsuji, J.
J. Am. Chem. Soc. 1989, 111, 4126. (b) Lou, S.; Westbrook, J. A.; Schaus,
S. E. J. Am. Chem. Soc. 2004, 126, 11440. (c) Lalic, G.; Aloise, A. D.; Shair,
M. D. J. Am. Chem. Soc. 2003, 125, 2852. (d) Magdziak, D.; Lalic, G.; Lee,
H. M.; Fortner, K. C.; Aloise, A. D.; Shair, M. D. J. Am. Chem. Soc. 2005,
127, 7284.
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E. C.; Tunge, J. A. Org. Lett. 2004, 6, 4113. (c) Behenna, D. C.; Stoltz, B. M.
J. Am. Chem. Soc. 2004, 126, 15044. (d) Trost, B. M.; Xu, J. Y. J. Am. Chem.
Soc. 2005, 127, 17180. (e) Burger, E. C.; Tunge, J. A. Org. Lett. 2004, 6, 4113.
(f ) Kuwano, R.; Ishida, N.; Murakami, M. Chem. Commun. 2005, 3951. (g)
Mohr, J. T.; Behenna, D. C.; Harned, A. M.; Stoltz, B. M. Angew. Chem., Int.
Ed. 2005, 44, 6924. (h) Nakamura, M.; Hajra, L.; Endo, K.; Nakamura, E.
Angew. Chem., Int. Ed. 2005, 44, 7248. (i) Trost, B. M.; Bream, R. N.; Xu, J.
Angew. Chem., Int. Ed. 2006, 45, 3109. ( j) McFadden, R. M.; Stoltz, B. M.
J. Am. Chem. Soc. 2006, 128, 7738. (k) Marinescu, S. C.; Nishimata, T.;
Mohr, J. T.; Stoltz, B. M. Org. Lett. 2008, 10, 1039. (l) Trost, B. M.; Xu, J.;
Schmidt, T. J. Am. Chem. Soc. 2008, 130, 11852.
(4) For selected papers on Pd-catalyzed intermolecular decarboxylative
cross-coupling reactions, see: (a) Goossen, L. J.; Goossen, K.; Rodrı
N.; Blanchot, M.; Linder, C.; Zimmermann, B. Pure Appl. Chem. 2008, 80,
1725. (b) Goossen, L. J.; Rodrıguez, N.; Goossen, K. Angew. Chem., Int. Ed.
´
guez,
´
2008, 47, 3100. (c) Tatamidani, H.; Yokota, K.; Kakiuchi, F.; Chatani, N.
J. Org. Chem. 2004, 69, 5615. (d) Gooβen, L. J.; Deng, G.; Levy, L. M.
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Becht, J.-M.; Drian, C. L. Org. Lett. 2008, 10, 3161. ( j) Shintani, R.; Park, S.;
Shirozu, F.; Murakami, M.; Hayashi, T. J. Am. Chem. Soc. 2008, 130, 16174.
(k) Shang, R.; Fu, Y.; Li, J.-B.; Zhang, S.-L.; Guo, Q.-X.; Liu, L. J. Am.
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Hirano, K.; Miura, M. Chem.;Eur. J. 2009, 15, 3674. (m) Xie, K.; Yang, Z.;
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DOI: 10.1021/jo1010284
r
Published on Web 06/25/2010
J. Org. Chem. 2010, 75, 5259–5264 5259
2010 American Chemical Society

Zhang et al.
JOCArticle
traditionally Sonogashira cross-coupling reaction because
they proceed via a CO2-released process under copper-free
conditions, avoiding the occurrence of the homocoupling.9
In 2008, Lee and co-workers first reported a Pd2(dba)3/dppf-
catalyzed cascade reaction of propiolic acid with aryl halides
involving a decarboxylation process (eq 1, Scheme 1).6a Sub-
sequently, they found that alkynyl carboxylic acids could
undergo the decarboxylative coupling with aryl iodides and
bromides with use of the Pd2(dba)3/dppb catalytic system
(eq 2, Scheme 1 ).6b Lee and Kim have also disclosed that
Pd2(dba)3 combined with phosphine ligand (PPh3 or Xant-
phos) were effective for the decarboxylative coupling be-
tween aryl halides (aryl iodides, bromides, and triflates) and
alkynyl carboxylic acids with the aid of Ag2O and LiX (X =
I, Cl) (eq 3, Scheme 1).6c As a continuing interest in the
decarboxylative coupling reactions,5k,8 we here report an
efficient palladium-catalyzed decarboxylative coupling route
to selectively synthesizing internal alkynes using both alkynyl
carboxylic acids and benzyl halides as the reaction partners
(eq 4, Scheme 1). Moreover, the reaction conditions are com-
patible with a wide range of aryl halides including less active
aryl chlorides.
SCHEME 1
TABLE 1. Screening Optimal Conditionsa
Results and Discussion
We began our investigation using readily available phe-
nylpropiolic acid (1a) and benzyl chloride (2a) as the model
substrates (Table 1). However, the results demonstrated that
the reaction between 1a and 2a was not successful under the
reported conditions (entry 1).6a,b After a series of trials,
we found that Pd(OAc)2 combined with dppb (L1) afforded
the desired decarboxylative coupling product 3 in 8% yield
with Cs2CO3 base and DMF medium (entries 2-4). To our
delight, the yield of 3 was enhanced to 36% when dppb was
replaced by PPh3 (L2) (entry 5). Encouraged by these results,
both solvents and reaction temperatures were evaluated to
obtain the optimal conditions (entries 6-9). It was disclosed
that MeCN has no effect on the decarboxylative coupling
reaction (entry 6), and THF displayed the highest efficiency
(entry 7). Among the reaction temperatures examined, it
turned out that the best results were obtained at 80 °C
(entries 7-9). Subsequently, the effect of three other ligands
entry ligand (mol %)
base
solvent T (°C) t (h) yield (%)
1b
2
3
4
5
6
7
8
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L2 (10)
L2 (10)
L2 (10)
L2 (10)
L2 (10)
L3 (10)
L3 (5)
L4 (5)
L5 (5)
L3 (5)
L3 (5)
L3 (5)
L3 (5)
L3 (5)
L3 (5)
L3 (2)
L4 (2)
L3 (2)
TBAF
TBAF
DMSO
DMSO
100
100
100
100
100
100
100
80
5
5
5
5
5
trace
trace
trace
8
Cs2CO3 DMSO
Cs2CO3 DMF
Cs2CO3 DMF
Cs2CO3 CH3CN
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 dioxane
36
5
5
trace
67
72
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
9
65
80
18
89
10
11
12
13
14
15
16
17
18
19c
20d
21d
22e
80
80
86
76
80
80
63
81
(5) For selected papers on Pd-catalyzed intramolecular decarboxylative
cross-coupling reactions, see: (a) Rayabarapu, D. K.; Tunge, J. A. J. Am.
Chem. Soc. 2005, 127, 13510. (b) Wang, C.; Tunge, J. A. Org. Lett. 2005, 7,
2137. (c) Burger, E. C.; Tunge, J. A. J. Am. Chem. Soc. 2006, 128, 10002. (d)
Waetzig, S. R.; Rayabarapu, D. K.; Weaver, J. D.; Tunge, J. A. Angew.
Chem., Int. Ed. 2006, 45, 4977. (e) Waetzig, S. R.; Tunge, J. A. J. Am. Chem.
Soc. 2007, 129, 4138. (f ) Waetzig, S. R.; Tunge, J. A. J. Am. Chem. Soc. 2007,
129, 14860. (g) Yeagley, A. A.; Chruma, J. J. Org. Lett. 2007, 9, 2879. (h)
Weaver, J. D.; Tunge, J. A. Org. Lett. 2008, 10, 4657. (i) Fields, W. H.; Khan,
A. K.; Sabat, M.; Chruma, J. J. Org. Lett. 2008, 10, 5131. ( j) Sim, S. H.; Park,
H.-J.; Lee, S. I.; Chung, Y. K. Org. Lett. 2008, 10, 433. (k) Huang, X.-C.;
Wang, F.; Liang, Y.; Li, J.-H. Org. Lett. 2009, 11, 1139.
Et3N
THF
80
80
78
65
K2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
Cs2CO3 THF
100
60
45
70
80
80
85
92
80
80
75
0
aReaction conditions: 1a (0.6 mmol), 2a (0.5 mmol), Pd(OAc)2 (5 mol
%), ligand (10 mol %), base (1.2 equiv), and solvent (2 mL). bPdCl2-
(PPh3)2 (5 mol %) instead of Pd(OAc)2. cPd(OAc)2 (3 mol %) was added.
dPd(OAc)2 (1 mol %) was added. eWithout Pd catalysis.
(6) (a) Moon, J.; Jeong, M.; Nam, H.; Ju, J.; Moon, J. H.; Jung, H. M.;
Lee, S. Org. Lett. 2008, 10, 945. (b) Moon, J.; Jang, M.; Lee, S. J. Org. Chem.
2009, 74, 1403. (c) Kim, H.; Lee, P. H. Adv. Synth. Catal. 2009, 351, 2827.
(7) For papers on Cu-catalyzed decarboxylation of 2-alkynoic acids, see:
L3-5 was tested (entries 10-13). We were pleased to observe
that three ligands L3-5 were effective for the reaction, and
Xphos (L3) was the most active ligand. Moreover, the
amount of L3 affected the reaction slightly (entries 10 and
11). With the Pd(OAc)2/L3 catalytic system in hand, a
number of experimental variables, such as solvent, base,
reaction temperature, and the Pd loading, were investigated
(entries 14-19). The yield of 3 was lowered by using dioxane
ꢀ
ꢁ
ꢁ
(a) Kolarovic, A.; Faberova, Z. J. Org. Chem. 2009, 74, 7199. (b) Jia, W.;
Jiao, N. Org. Lett. 2010, 12, 2000. (c) Yu, M.; Pan, D.; Jia, W.; Chen, W.;
Jiao, N. Tetrahedron Lett. 2010, 51, 1287.
(8) Pi, S.-F.; Tang, B.-X.; Li, J.-H.; Liu, Y.-L.; Liang, Y. Org. Lett. 2009,
11, 2309.
(9) For selected reviews on the Sonogashira cross-coupling reaction, see:
(a) Sonogashira, K. J. Organomet. Chem. 2002, 653, 46. (b) Negishi, E.-i.;
Anastasia, L. Chem. Rev. 2003, 103, 1979. (c) Nicolaou, K. C.; Bulger, P. G.;
ꢁ
Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4442. (d) Chinchilla, R.; Najera,
C. Chem. Rev. 2007, 107, 874.
5260 J. Org. Chem. Vol. 75, No. 15, 2010

Zhang et al.
JOCArticle
solvent, Et3N or K2CO3 bases (entries 14-16). The reaction
temperatures have a fundamental influence on the reaction,
and the yield was decreased at either 100 or 60 °C (entries 17
and 18). It was interesting to discover that in the presence of
L3 the highest yield was isolated at a loading of 1 mol % of
Pd(OAc)2 (entries 10, 19, and 20), but 1 mol % of Pd(OAc)2
combined L4 gave the same yield with that of 5 mol % of
Pd(OAc)2 (entry 12 vs entry 21). However, the reaction
cannot take place without Pd catalysis (entry 22).
TABLE 2. Pd(OAc)2/L3-Catalyzed Decarboxylative Coupling of
Alkynyl Carboxylic Acids (1) with Halides or Acetates (2)a
As shown in Table 2, the decarboxylative coupling reac-
tions of alkynyl carboxylic acids with various benzyl chlo-
rides were carried out in the presence of Pd(OAc)2, L3, and
Cs2CO3. Initially, a variety of substituted benzyl chlorides
2b-g were investigated for the reaction with phenylpropiolic
acid (1a) (entries 1-6). The results indicated that a number
of functional groups, including methyl, ether, chloro, and
fluoro, on the aryl moiety were tolerated well under the
standard conditions, but the electron-deficient NO2 group
was not suitable. Substrate 2b bearing an o-methylphenyl
group, for instance, underwent the decarboxylative coupling
reaction with acid 1a, Pd(OAc)2, and L3 smoothly, affording
the corresponding product 4 in 80% yield (entry 1). Mode-
rate yields were still achieved from the reaction of either
p-chloro-substituted substrates 2e or o-fluoro-substituted
2f (entries 4 and 5). However, acid 1a cannot react with
1-(chloromethyl)-4-nitrobenzene (2g) under the same condi-
tions and provide the home-coupling product 1,4-diphenyl-
buta-1,3-diyne in 55% yield (based on alkyne) (entry 6). The
reason may be that the electron-withdrawing group deacti-
vated benzyl chloride leading to the home-coupling superior
to the cross-coupling process. We were happy to find that
benzyl bromide (2h) was also consistent with the optimal
conditions leading to 88% yield (entry 7), but benzyl acetate
(2i) was not a suitable substrate (entry 8). Interestingly,
cinnamyl halides 2j-l, (E)-(3-chloroprop-1-enyl)benzene
(2j), (E)-(3-bromoprop-1-enyl)benzene (2k), and cinnamyl
acetate (2l), successfully underwent the decarboxylative coup-
ling with acid 1a, Pd(OAc)2, and L3 in 72%, 69%, and 80%
yields, respectively (entries 9-11). To our delight, the opti-
mal conditions were found to be compatible with various
alkynyl carboxylic acids 1b-f, including substituted aryl and
aliphatic propiolic acids (entries 12-22). For example, ary-
lalkynyl carboxylic acids 1b-d, with a methyl, chloro or
acetyl group on the aryl moiety, were reacted with benzyl
chloride (2a), Pd(OAc)2, L3, and Cs2CO3 smoothly in good
yields (entries 12-14). Gratifyingly, both oct-2-ynoic acid
(1e) and but-2-ynoic acid (1f) were also successful for the
decarboxylative coupling reaction with 5-chloromethyl-
benzo[1,3]dioxole (2d), and afforded the corresponding pro-
ducts 17 and 21 in 88% and 83% yields, respectively (entries 18
and 22). It is noteworthy that NO2-substituted chloride 2g is
suitable for the reaction with acid 1b (entry 21). However, an
attempt at the decarboxylative coupling reaction of terminal
propiolic acid 1g with chloride 2d failed (entry 23).
Next, we tested the optimal conditions for the decarboxy-
lative coupling reactions of alkynyl carboxylic acids 1 with
numerous aryl halides 2m-w, and the results are summa-
rized in Table 3.6 In the presence of Pd(OAc)2, L3, and
Cs2CO3, a variety of aryl halides, including less active aryl
chloride, successfully underwent the reaction with acid 1a
in moderate to good yields. Initially, the reactions of acid 1a
with iodobenzene (2m) or 1-iodo-4-methoxybenzene (2n)
aReaction conditions: 1 (0.6 mmol), 2 (0.5 mmol), Pd(OAc)2 (1 mol
%), L3 (2 mol %), Cs2CO3 (1.2 equiv), and THF (2 mL) at 80 °C for 10 h.
bThe home-coupling product, 1,4-diphenylbuta-1,3-diyne, was obtained
in 55% yield (based on alkyne) together with some side products.
J. Org. Chem. Vol. 75, No. 15, 2010 5261

Zhang et al.
JOCArticle
TABLE 3. Pd(OAc)2/L3-Catalyzed Decarboxylative Coupling of
3-Phenylpropiolic Acid (1a) with Aryl Halides (2)a
SCHEME 2
is general, and its scope was extended to benzyl halides,
cinnamyl halides, and aryl halides including less active aryl
chlorides, and (2) this reaction was carried out under rela-
tively low loading Pd(OAc)2 conditions.
Experimental Section
Typical Experimental Procedure for the Pd(OAc)2/Xphos
(L3)-Catalyzed Decarboxylative Coupling Reaction. Acid 1 (0.6
mmol), Chloride 2 (0.5 mmol), Pd(OAc)2 (1 mol %, 1.1 mg), L3
(2 mol %, 3.9 mg), Cs2CO3 (1.2 equiv, 195.6 mg), and THF
(2 mL) were added to a Schlenk tube in turn. Then the solution
was stirred at 80 °C under nitrogen atmosphere for the indicated
time until complete consumption of starting material as moni-
tored by TLC and GC-MS analysis. After the reaction was
finished, the mixture was washed with brine, extracted with
diethyl ether, dried over anhydrous Na2SO4, and evaporated in
vacuum. The residue was purified by flash column chromato-
graphy on silica gel (hexane/ethyl acetate) to afford the desired
product.
Prop-1-yne-1,3-diyldibenzene (3):10 colorless oil; 1H NMR
(300 MHz, CDCl3) δ 7.46-7.39 (m, 4H), 7.34-7.22 (m, 6H),
3.81 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 136.7, 131.6, 128.5,
128.2, 127.9, 127.8, 126.6, 123.6, 87.5, 82.6, 25.7; LRMS (EI,
70 eV) m/z (%) 192 (Mþ, 100), 191 (91), 189 (30).
1-Methyl-2-(3-phenylprop-1-ynyl)benzene (4):10 colorless oil;
1H NMR (300 MHz, CDCl3) δ 7.48-7.41 (m, 4H), 7.29-7.25
(m, 2H), 7.20-7.15 (m, 2H), 3.72 (s, 2H), 2.34 (s, 3H); 13C NMR
(125 MHz, CDCl3) δ 136.0, 134.9, 131.6, 130.0, 128.3, 128.2,
127.7, 126.8, 126.2, 123.7, 87.2, 82.7, 23.9, 19.3; LRMS (EI,
70 eV) m/z (%) 206 (Mþ, 70), 191 (67), 128 (42), 91 (100).
1-Methoxy-3-(3-phenylprop-1-ynyl)benzene (5):11 colorless oil;
1H NMR (300 MHz, CDCl3) δ 7.46-7.43 (m, 2H), 7.30-
7.22 (m, 4H), 7.00-6.98 (m, 2H), 6.80-6.79 (m, 1H), 3.80-3.76
(m, 5H); 13C NMR (125 MHz, CDCl3) δ 159.8, 138.3, 131.6,
129.5, 128.2, 127.8, 123.6, 120.3, 113.7, 120.0, 87.3, 82.7, 55.1, 25.7;
LRMS (EI, 70 eV) m/z (%) 222 (Mþ, 100), 207 (64), 178 (63).
5-(3-Phenylprop-1-ynyl)benzo[d][1,3]dioxole (6): colorless oil;
1H NMR (300 MHz, CDCl3) δ 7.45-7.43 (m, 2H), 7.42-7.26
(m, 3H), 6.91-6.82 (m, 2H), 6.76 (d, J = 7.9 Hz, 1H), 5.91
(s, 2H), 3.72 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 147.7,
146.2, 131.6, 130.4, 128.2, 127.8, 123.5, 120.7, 108.5, 108.1,
100.9, 87.6, 82.6, 25.3; LRMS (EI, 70 eV) m/z (%) 236 (Mþ,
100), 178 (80), 206 (29); HRMS (EI) for C16H12O2 (Mþ) calcd
236.0837, found 236.0835.
aReaction conditions: 1a (0.6 mmol), 2 (0.5 mmol), Pd(OAc)2 (1 mol
%), L3 (2 mol %), Cs2CO3 (1.2 equiv), and THF (2 mL) at 80 °C for 10 h.
bFor 24 h.
were carried out smoothly to afford the target alkynes 23 and
24 in moderate yields together with the homocoupling pro-
ducts (about 10% yields) from aryl iodides (entries 1 and 2).
Interestingly, good yields were isolated with use of bromo-
benzene (2o) or 2-bromothiophene (2p) as one of the reaction
partners under the same conditions (entries 2 and 3). We
were pleased to find that several functional groups, such as
formyl, acetyl, ester, or nitro group, on the aryl ring were
tolerated (entries 5-8). For instance, 6-bromobenzo[1,3]-
dioxole-5-carbaldehyde (2q) was treated with acid 1a,
Pd(OAc)2, L3, and Cs2CO3 in 81% yield (entry 5). To our
delight, satisfactory yields were still achieved after 24 h for
less active aryl chlorides 2u and 2w under the optimal con-
ditions (entries 9 and 11). However, deactivated 1-chloro-
4-methoxybenzene (2v) displayed less efficiency (entry 10).
As shown in Scheme 2, phenylacetylene (30) could proceed
with the Sonogashira cross-coupling reaction with benzyl
chloride providing a good yield in the presence of Pd(OAc)2,
L3, and Cs2CO3.
In summary, we have developed a palladium-catalyzed
decarboxylative coupling protocol for selectively preparing
internal benzyl alkynes and 1,2-diaryl alkynes. In the pre-
sence of Pd(OAc)2 and Xphos (L3), alkynyl carboxylic acids
smoothly underwent the reaction with benzyl halides and
aryl halides in moderate to good yields. Compared with the
previous reported results of palladium-catalyzed decarboxy-
lative coupling, two features were established: (1) This reaction
1-Chloro-4-(3-phenylprop-1-ynyl)benzene (7):10 colorless oil;
1H NMR (300 MHz, CDCl3) δ 7.45-7.42 (m, 2H), 7.34-7.27
(m, 7H), 3.77 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 135.2,
132.4, 131.6, 129.3, 128.6, 128.2, 127.9, 123.8, 86.8, 83.0, 25.1;
LRMS (EI, 70 eV) m/z (%) 226 (Mþ, 28), 189 (30), 191 (100).
1-Fluoro-2-(3-phenylprop-1-ynyl)benzene (8): colorless oil; 1H
NMR (300 MHz, CDCl3) δ 7.59-7.45 (m, 3H), 7.30-7.02 (m,
6H), 3.84(s, 2H);13C NMR (125 MHz, CDCl3) δ160.6 (d, 1JC,F
=
=
245 Hz, 1C), 131.6, 129.9 (d, 3JC,F = 3.8 Hz, 1C), 128.4 (d, 3JC,F
4
8.8 Hz, 1C), 128.2, 127.9, 124.2, (d, JC,F = 2.5 Hz, 1C), 123.8
(10) (a) Li, C.; Li, W.; Wang, J. Tetrahedron Lett. 2009, 50, 2533. (b)
Adjabeng, G.; Brenstrum, T.; Frampton, C. S.; Robertson, A. J.; Hillhous,
J.; McNulty, J.; Capretta, A. J. Org. Chem. 2004, 69, 5082. (c) Li, C.; Wang, J.
J. Org. Chem. 2007, 72, 7431.
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(d, 2JC,F = 15 Hz, 1C), 123.4, 115.0 (d, 2JC,F = 21.3 Hz, 1C), 86.0,
83.0, 19.1; LRMS (EI, 70 eV) m/z (%) 210 (Mþ, 100), 209 (78), 189
(29); HRMS (EI) for C15H11F (Mþ) calcd 210.0845, found
210.0844.
2.23-2.19 (m, 2H), 1.54-1.50 (m, 2H), 1.40-1.30 (m, 4H), 0.90
(t, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 136.1, 132.1,
129.8, 128.4, 83.1, 76.9, 31.1, 28.6, 24.5, 22.2, 18.7, 13.9; LRMS
(EI, 70 eV) m/z (%) 220 (Mþ, 22), 129 (100), 128 (42).
(E)-Pent-1-en-4-yne-1,5-diyldibenzene (10):12 colorless oil; 1H
NMR (300 MHz, CDCl3) δ 7.47-7.20 (m, 10H), 6.70 (d,
J = 15.7 Hz, 1H), 6.25-6.20 (dt, J = 5.6 Hz, 15.7 Hz, 1H),
3.39 (dd, J = 1.8 Hz, 5.6 Hz, 2H); 13C NMR (125 MHz, CDCl3)
δ 137.1, 131.6, 131.4, 128.5, 128.2, 127.8, 127.3, 126.3, 124.2,
123.7, 86.7, 82.8, 23.0; LRMS (EI, 70 eV) m/z (%) 218 (Mþ,
100), 202 (94), 217 (91).
1-Fluoro-2-(oct-2-ynyl)benzene (19): yellow oil; 1H NMR (300
MHz, CDCl3) δ: 7.54-7.53 (m, 1H), 7.18-7.10 (m, 2H),
7.02-6.98 (m, 1H), 3.59 (s, 3H), 2.24-2.20 (m, 2H), 1.54-
1.51 (m, 2H), 1.39-1.31 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H); 13
C
1
NMR (125 MHz, CDCl3) δ 160.6, (d, JC,F = 245 Hz, 1C),
129.8, (d, 3JC,F = 3.8 Hz, 1C), 128.1 (d, 3JC,F = 7.5 Hz, 1C), 124.8
2
4
(d, JC,F = 16.3 Hz, 1C), 124.0, (d, JC,F = 3.8 Hz, 1C), 114.9
(d, 2JC,F = 21.8 Hz, 1C), 83.1, 76.0, 31.1, 28.7, 22.4, 18.8, 18.5,
14.0; LRMS (EI, 70 eV) m/z (%) 204 (Mþ, 31), 147 (98), 95
(100); HRMS (EI) for C14H17F (Mþ) calcd 204.1314, found
204.1310.
1-Methyl-4-(3-phenylprop-1-ynyl)benzene (11):10 colorless oil;
1H NMR (300 MHz, CDCl3) δ 7.43-7.41 (d, J = 7.2 Hz, 2H),
7.36-7.25 (m, 5H), 7.11-7.08 (d, J = 7.8Hz, 2H); 13C NMR (125
MHz, CDCl3) δ 137.8, 136.9, 131.5, 123.0, 128.5, 127.9, 126.6,
120.6, 86.7, 82.7, 25.7, 21.4; LRMS (EI, 70 eV) m/z (%) 206 (Mþ,
100), 205 (73), 176 (48).
1-Nitro-4-(oct-2-ynyl)benzene (20): yellow oil; 1H NMR (300
MHz, CDCl3) δ: 8.19-8.16 (m, 2H), 7.54-7.51 (m, 2H), 3.69-
3.68 (m, 2H), 2.26-2.21 (m, 2H), 1.55-1.52 (m, 2H), 1.38-1.32
(m, 4H), 0.91 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
128.6, 123.6, 84.2, 75.7, 31.1, 28.5, 25.6, 22.2, 18.7, 14.0; LRMS
(EI, 70 eV) m/z (%) 231 (Mþ, 3), 128 (86), 95 (100); HRMS (EI)
for C14H17NO2 (Mþ) calcd 231.1259, found 231.1257.
5-(But-2-ynyl)benzo[d][1,3]dioxole (21): colorless oil; 1H NMR
(300 MHz, CDCl3) δ 6.84 (s, 1H), 6.78-6.72 (m, 2H), 5.92 (s,
2H), 3.45 (s, 2H), 1.84 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ 147.6, 146.0, 131.3, 120.6, 108.5, 108.0, 100.8, 77.74, 76.87,
24.7, 3.5; LRMS (EI, 70 eV) m/z (%) 174 (Mþ, 100), 115 (93), 116
(59); HRMS (EI) for C11H10O2 (Mþ) calcd. 174.0681, found
174.0680.
1-Chloro-4-(3-phenylprop-1-ynyl)benzene (12):13 colorless oil;
1H NMR (300 MHz, CDCl3) δ 7.41-7.25 (m, 9H), 3.82 (s, 2H);
13C NMR (125 MHz, CDCl3) δ 136.5, 133.8, 132.9, 128.6, 127.9,
126.7, 122.2, 88.6, 81.5, 25.7; LRMS (EI, 70 eV) m/z (%) 226 (Mþ,
50), 191 (100), 190 (25).
1-(4-(3-Phenylprop-1-ynyl)phenyl)ethanone (13): colorless oil;
1H NMR (300 MHz, CDCl3) δ 7.89-7.87 (m, 2H), 7.52-7.49
(m, 2H), 7.41-7.34 (m, 4H), 7.32-7.25 (m, 1H); 13C NMR (125
MHz, CDCl3) δ 197.3, 136.2, 135.9, 131.7, 128.6, 128.5, 128.1,
127.9, 126.8, 91.3, 82.0, 26.5, 25.8; LRMS (EI, 70 eV) m/z (%)
234 (Mþ, 71), 219 (100), 191 (52); HRMS (EI) for C17H14O (Mþ)
calcd 234.1045, found 234.1041.
Oct-2-ynylbenzene (14):14 colorless oil; 1H NMR (300 MHz,
CDCl3) δ 7.36-7.27 (m, 4H), 7.23-7.21 (m, 1H), 3.58 (t, J = 2.2
Hz, 2H), 2.23-2.19 (m, 2H), 1.56-1.51 (m, 2H), 1.39-1.31 (m,
4H), 0.90 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
137.6, 128.3, 127.8, 126.3, 82.7, 77.4, 31.1, 28.7, 25.1, 22.2, 18.8,
14.0; LRMS (EI, 70 eV) m/z (%) 186 (Mþ, 28), 130 (67), 129
(100).
1,2-Diphenylethyne (23):10 white solid, mp 58.5-60.8 (lit. mp
59-60 °C); 1H NMR (300 MHz, CDCl3) δ 7.60-7.51 (m, 4H),
7.39-7.26 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 132.0, 128.7,
128.6, 123.7, 89.7; LRMS (EI, 70 eV) m/z (%) 178 (Mþ, 100).
1-Methoxy-4-(2-phenylethynyl)benzene (24):10 white solid,
mp 55.1-57.8 (lit. mp 56-58 °C); 1H NMR (400 MHz, CDCl3)
δ 7.52-7.51 (m, 2H), 7.48 (d, J = 9.0 Hz, 2H), 7.34-7.32 (m,
3H), 6.88 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 159.6, 133.0, 131.4, 128.3, 127.9, 123.6, 115.4, 114.0,
89.4, 88.1, 55.3; LRMS (EI, 70 eV) m/z (%) 208 (Mþ, 100).
2-(Phenylethynyl)thiophene (25):15 colorless oil; 1H NMR (300
MHz, CDCl3) δ 7.51-7.50 (d, J = 3.9 Hz, 2H), 7.34-7.24 (m,
5H), 7.02-6.99 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 131.8,
;131.4, 128.4, 127.2, 127.1, 123.3, 122.9, 93.0, 82.3; LRMS (EI,
70 eV) m/z (%) 184 (Mþ, 100), 139 (28), 152 (24).
1
1-Methyl-2-(oct-2-ynyl)benzene (15): colorless oil; H NMR
(300 MHz, CDCl3) δ 7.45-7.42 (m, 1H), 7.23-7.12 (m, 3H),
3.48 (t, J = 2.2 Hz, 2H), 2.30 (s, 3H), 2.22-2.19 (m, 2H),
1.52-1.50 (m, 2H), 1.40-1.30 (m, 4H), 0.90 (t, J = 6.9 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ 135.8, 129.9, 128.1, 126.6, 126.0,
82.7, 77.1, 31.1, 28.7, 23.3, 22.2, 18.8, 13.9; LRMS (EI, 70 eV) m/
z (%) 200 (Mþ, 24), 128, (43), 129 (100); HRMS (EI) for C15H20
(Mþ) calcd 200.1565, found 200.1561.
1-Methoxy-3-(oct-2-ynyl)benzene (16): colorless oil; 1H NMR
(300 MHz, CDCl3) δ 7.24-7.19 (m, 1H), 6.93-6.91 (m, 2H),
6.78-6.74 (m, 1H), 3.80 (s, 3H), 3.56 (t, J = 2.2 Hz, 2H), 2.23-
2.19 (m, 2H), 1.53-1.50 (m, 2H), 1.38-1.33 (m, 4H), 0.90 (t, J =
7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 159.7, 139.2, 129.3,
120.2, 113.4, 111.8, 82.8, 77.3, 55.1, 31.1, 28.7, 25.1, 22.2, 18.8,
14.0; LRMS (EI, 70 eV) m/z (%) 216 (Mþ, 100), 115 (53), 116
(40); HRMS (EI) for C15H20O (Mþ) calcd 216.1514, found
216.1516.
6-(Phenylethynyl)benzo[d][1,3]dioxole-5-carbaldehyde (26):16
yellow solid, mp 128.1-130.2 °C (lit. mp 128-130 °C); 1H
NMR (300 MHz, CDCl3) δ 10.49 (s, 1H), 7.54-7.52 (m, 2H),
7.39-7.37 (m, 4H), 7.03 (s, 1H), 6.09 (s, 1H); 13C NMR (125
MHz, CDCl3) δ 190.0, 152.4, 148.7, 132.1, 131.6, 128.9, 128.5,
123.3, 111.9, 106.1, 102.4, 95.1, 84.8; LRMS (EI, 70 eV) m/z (%)
250 (Mþ, 100), 163 (53), 164 (33).
2-(Phenylethynyl)benzaldehyde (27):17 colorless oil; 1H NMR
(300 MHz, CDCl3) δ 10.65 (s, 1H), 7.96-7.30 (d, J = 7.8 Hz,
1H), 7.65-7.55 (m, 4H), 7.46-7.37 (m, 4H); 13C NMR (125
MHz, CDCl3) δ 190.6, 135.8, 133.7, 133.2, 131.6, 129.0, 128.6,
128.5, 127.2, 126.8, 122.3, 96.3, 84.9; LRMS (EI, 70 eV) m/z (%)
206 (Mþ, 100), 178 (47), 176 (43).
5-(Oct-2-ynyl)benzo[d][1,3]dioxole (17): colorless oil; 1H NMR
(300 MHz, CDCl3) δ 6.85-6.71 (m, 3H), 5.91 (s, 2H), 3.48 (t, J =
2.4 Hz, 2H), 2.22-2.17 (m, 2H), 1.54-1.50 (m, 2H), 1.39-1.31
(m, 4H), 0.90 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
147.6, 146.0, 131.4, 120.5, 108.4, 108.0, 100.8, 82.6, 77.6, 31.1, 28.7,
24.8, 22.2, 18.7, 13.9; LRMS (EI, 70 eV) m/z (%) 230 (Mþ, 100),
115(53), 116 (40);HRMS(EI) for C15H18O2 (Mþ) calcd 230.1307,
found 230.1304.
1-(4-(Phenylethynyl)phenyl)ethanone (28):10 yellow solid, mp
1
95.5-98.0 (lit. mp 95-97 °C); H NMR (300 MHz, CDCl3) δ
7.96-7.93 (d, J = 8.4 Hz, 2H), 7.63-7.55 (m, 4H), 7.38-7.26
(m, 1H); 13C NMR (125 MHz, CDCl3) δ 197.3, 136.2, 131.7,
131.6, 128.8, 128.4, 128.3, 128.2, 122.6, 92.7, 88.6, 26.6; LRMS
(EI, 70 eV) m/z (%) 220 (Mþ, 70), 205 (100), 176 (46).
1-Chloro-4-(oct-2-ynyl)benzene (18):14 colorless oil; 1H NMR
(300 MHz, CDCl3) δ 7.26 (m, 4H), 3.53 (t, J = 2.4 Hz, 2H),
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Chem. Soc., Perkin Trans. 2 1972, 192.
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J. Org. Chem. Vol. 75, No. 15, 2010 5263

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Methyl 5-nitro-2-(phenylethynyl)benzoate (29):18 yellow solid;
Acknowledgment. The authors thank the National Nat-
ural Science Foundation of China (No. 20872112) and
Zhejiang Provincial Natural Science Foundation of China
(No. Y407116) for financial support.
1
mp 71.9-74.0 °C; H NMR (300 MHz, CDCl3) δ 8.84 (s, 1H),
8.33 (d, J = 8.5 Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.62-7.61 (m,
2H), 7.41 (s, 1H), 4.02 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
164.5, 146.3, 134.9, 132.7, 132.0, 130.3, 129.6, 128.5, 126.0, 125.8,
122.2, 100.4, 86.9, 52.8; LRMS (EI, 70 eV) m/z (%) 281 (Mþ, 100),
266 (60), 220 (34).
Supporting Information Available: Copies of spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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5264 J. Org. Chem. Vol. 75, No. 15, 2010