Palladium-catalyzed cross-coupling of electron-poor terminal alkynes with arylboronic acids under ligand-free and aerobic conditions

Article abstract of DOI:10.1021/jo101063p

Palladium-catalyzed cross-coupling reaction of terminal alkynes with arylboronic acids has been described. In the presence of Pd(OAc)₂ and Ag₂O, a variety of terminal alkynes, including electron-poor terminal alkynes, smoothly underwent the reaction with numerous boronic acids to afford the corresponding internal alkynes in moderate to good yields. Moreover, this methodology was applied to the synthesis of 1H-isochromenes and diynes. It is noteworthy that the reaction proceeds under ligand-free and relative lower loading Pd conditions, and the maximal TONs (turnover numbers) of the reaction are up to 720,000.

Full text of DOI:10.1021/jo101063p

pubs.acs.org/joc
Palladium-Catalyzed Cross-Coupling of Electron-Poor Terminal Alkynes
with Arylboronic Acids under Ligand-Free and Aerobic Conditions
Ming-Bo Zhou, Wen-Ting Wei, Ye-Xiang Xie, Yong Lei, and Jin-Heng Li*
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education),
Hunan Normal University, Changsha 410081, China
jhli@hunnu.edu.cn
Received June 1, 2010
Palladium-catalyzed cross-coupling reaction of terminal alkynes with arylboronic acids has been
described. In the presence of Pd(OAc)2 and Ag2O, a variety of terminal alkynes, including electron-
poor terminal alkynes, smoothly underwent the reaction with numerous boronic acids to afford the
corresponding internal alkynes in moderate to good yields. Moreover, this methodology was applied
to the synthesis of 1H-isochromenes and diynes. It is noteworthy that the reaction proceeds under
ligand-free and relative lower loading Pd conditions, and the maximal TONs (turnover numbers) of
the reaction are up to 720,000.
Introduction
methods for constructing this skeleton, the Sonogashira
cross-coupling reaction represents the most straightforward
and efficient tool and has been widely explored since it was
reported by Sonogashira, Cassar, and Heck independently.3-5
Although many modified transformations have been reported
for these purposes,3-5 some limitations still remained: elec-
tron-poor alkynes usually give unsatisfactory results from
the reaction with aryl halides. To overcome these limitations,
Zou and co-workers reported a procedure for construct-
ing internal alkynes through the cross-coupling of terminal
alkynes with arylboronic acids using a palladium/silver system
(eq 1, Scheme 1).6 In the presence of (dppf)PdCl2 and Ag2O,
terminal alkynes including an electron-poor alkyne (ethyl
propiolate) underwent reaction with arylboronic acids at
room temperature for 20-30 h, providing the corresponding
The alkyne skeleton is a prevalent motif found in many
naturally occurring products1 and materials.2 Among the
(1) For reviews, see: (a) Bohlmann, F.; Burkhart, F. T. Zero, C. Naturally
Occurring Acetylenes; Academic: London, 1973. (b) Hunstman, V. D. The
Chemistry of the Carbon-Carbon Triple Bond; Patai, S., Ed.; Wiley-Inter-
science: London, 1978; p 553. (c) Nicolaou, K. C.; Bulger, P. G.; Sarl-ah, D.
Angew. Chem., Int. Ed. 2005, 44, 4442.
(2) For selected reviews and papers, see: (a) Bunz, U. H. F. Chem. Rev.
2000, 100, 1605. (b) Tour, J. M. Acc. Chem. Res. 2000, 33, 791. (c) Siemsen,
P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39, 2632.
(d) Martin, R. E.; Diederich, F. Angew. Chem., Int. Ed. 1999, 38, 1350.
(3) For selected reviews, see: (a) Sonogashira, K.; Tohda, Y.; Hagihara,
N. Tetrahedron Lett. 1975, 16, 4467. (b) Sonogashira, K. In Metal-Catalyzed
Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998; p 203. (c) Moore, J. S. Acc. Chem. Res. 1997, 30, 402.
(d) Sonogashira, K. J. Organomet. Chem. 2002, 653, 46. (e) Tykwinski, R. R.
Angew. Chem., Int. Ed. 2003, 42, 1566. (f) Negishi, E.; Anastasia, L. Chem.
Rev. 2003, 103, 1979. (g) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.;
Diederich, F., de Meijere, A., Eds.; Wiley-VCH: Weinheim, 2004.
(h) Transition Metals for Organic Synthesis; Building Block and Fine Chemicals,
2nd ed.; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004. (i) Nicolaou,
K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4442. (j) Yin,
L.; Liebscher, J. Chem. Rev. 2007, 107, 133. (k) Doucet, H.; Hierso, J.-C.
(4) (a) Diek, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93, 259.
(b) Cassar, L. J. Organomet. Chem. 1975, 93, 253. (c) Sonogashira, K.;
Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467. (d) Tang, B.-X.;
Tang, D.-J.; Tang, S.; Yu, Q.-F.; Zhang, Y.-H.; Liang, Y.; Zhong, P.; Li,
J.-H. Org. Lett. 2008, 10, 1063. (e) Jiang, T.-S.; Zhang, X.-G.; Li, J.-H.
Synthesis 2009, 3029. (f) Pinto, A.; Neuville, L.; Retailleau, P.; Zhu, J. Org.
Lett. 2006, 8, 4927. (g) Pinto, A.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed.
2007, 46, 3291.
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Angew. Chem., Int. Ed. 2007, 46, 834. (l) Chinchilla, R.; Najera, C. Chem. Rev.
2007, 107, 874.
DOI: 10.1021/jo101063p
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Published on Web 07/22/2010
J. Org. Chem. 2010, 75, 5635–5642 5635
2010 American Chemical Society

Zhou et al.
JOCArticle
SCHEME 1
generated alkynylzinc derivatives, were required.9 Thus, the
development of a general and ligand-free method for extend-
ing the electron-poor alkyne scope is interesting. Here, we report
a palladium-catalyzed cross-coupling of terminal alkynes, in-
cluding electron-poor terminal alkynes, with boronic acids under
ligand-free and relatively lower loading Pd conditions (eq 3,
Scheme 1). It is noteworthy that the maximum TONs (turnover
numbers) of the reaction are up to 720000.
Results and Discussion
The reaction between N-methyl-N-phenylpropiolamide
(1a) and phenylboronic acid (2a) was chosen as a model
reaction to screen the optimal reaction conditions, and the
results are summarized in Table 1. To our delight, treatment
of amide 1a with 2a, Pd(OAc)2 (0.1 mol %), Ag2O (1 equiv),
and CH3ONa (1 equiv) afforded the desired product 4 in
61% yield after 12 h (entry 1). Identical results were observed
at a loading of 0.01 mol % of Pd(OAc)2 (entry 2). Subse-
quently, both the amount of Ag2O and the effect of bases
were investigated (entries 3-12). We found that the reaction
could not take place without Ag (entry 6), and 1.5 equiv of
Ag2O gave the best results in the presence of 2 equiv of
K2CO3 base (entry 8). The other bases, including Na2CO3,
Cs2CO3, and KOAc, affected the reaction slightly (entries
9-11). The results demonstrated that a moderate yield was
still isolated using Ag2O alone (entry 12). Two other sol-
vents, n-PrCN and toluene, were tested, and they were less
effective than MeCN (entries 13 and 14). Among the reaction
temperatures examined, 70 °C provided the highest yield
(entries 8 and 15-17). While 70 °C afforded the target
product 4 in 88% yield (entry 15), both 100 and 50 °C
decreased the yield slightly (entries 8 and 16). Gratifyingly,
72% yield of 4 was still achieved at room temperature after a
prolonged time (48 h, entry 17). It is noteworthy that
satisfactory yield can be obtained for 48 h even at 0.0001
mol % of Pd(OAc)2 (TONs = 720000, entry 18), but no
reaction is observed without Pd catalysis (entry 19). Either
PdCl2 or PdCl2/dppf were suitable catalysts for the reaction,
but they were inferior to Pd(OAc)2 (entries 20 and 21).
Finally, four other Ag salts were also evaluated, and they
displayed less efficiency by comparison with Ag2O (entries
22-25).10 It is noteworthy that in the absence of K2CO3 a
moderate yield can be isolated using 0.01 mol % of Pd(OAc)2
and 3.5 equiv of Ag2CO3 (entry 25).
internal alkynes in moderate to good yields. However, the
reaction required high loading of (dppf)PdCl2 (5 mol %) and
phenylacetylene displayed less activity for the cross-coupling
process. Subsequently, Wu and co-workers extended the scope
to arylalkynes using the cyclopalladated ferrocenylimine and
Ag2O system (eq 2, Scheme 1).7 Although both the aforemen-
tioned catalytic systems were efficient and provided an alter-
native route to internal alkynes, only an electron-poor alkyne
was examined and highly expensive palladium-ligand cata-
lytic systems were required.8
Generally, N,3-diarylpropiolamides can be prepared by
the traditional Sonongashira method using electron-poor
alkynes and aryl halides as the reaction partners; however,
the yields are usually low to moderate based on the pro-
perties of both alkynes and aryl halides.4 For example,
treatment of N-methyl-N-phenylpropiolamide (1a) with io-
dobenzene, PdCl2(PPh3)2 (5 mol %), and CuI (10 mol %) in
Et3N/THF afforded the desired product 3 in 62% yield at
room temperature and 51% at 70 °C (Scheme 2).4d-g How-
ever, only a moderate yield was achieved for high active
1-(4-iodophenyl)ethanone under the same conditions. On
the other hand, the Sonogashira cross-coupling reactions of
ynones with aryl iodides cannot take place under the tradi-
tional Sonongashira conditions. To realize these reactions,
some special reagents, such as diaryliodonium salts or in situ
As shown in Table 2, the scope of the alkynes and boronic
acids was explored under the optimal reaction conditions.
Initially, a variety of boronic acids 2 were investigated by
reaction with N-methyl-N-phenylpropiolamide (1a) (entries
1-12). The results demonstrated that several functional
groups, including methyl, methoxy, fluoro, iodo, formyl,
acetyl, nitro, and vinyl groups, on the aryl moiety of sub-
strates 2 were perfectly tolerated. For example, methyl-
substituted arylboronic acids 2b-d smoothly underwent
(5) For selected papers, see: (a) Liang, B.; Dai, M.; Chen, J.; Yang, Z.
J. Org. Chem. 2005, 70, 391. (b) Li, J.-H.; Liang, Y.; Xie, Y.-X. J. Org. Chem.
2005, 70, 4393. (c) Li, J.-H.; Hu, X.-C; Xie, Y.-X. Tetrahedron 2006, 62, 31.
(d) Li, J.-H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu,
X.-C. J. Org. Chem. 2007, 72, 2053. (e) Cheng, J.; Sun, Y.; Wang, F.; Guo,
M.; Xu, J.-H.; Pan, Y.; Zhang, Z. J. Org. Chem. 2004, 69, 5428. (f) Zhang, W.;
Wu, H.; Liu, Z.; Zhong, P.; Zhang, L.; Huang, X.; Cheng, J. Chem. Commun.
2006, 4826. (g) Gelman, D.; Buchwald, S. L. Angew. Chem., Int. Ed. 2003, 42,
5993. (h) Mino, T.; Shirae, Y.; Saito, T.; Sakamoto, M.; Fujita, T. J. Org.
Chem. 2006, 71, 9499. (i) Ma, D.; Liu, F. Chem. Commun. 2004, 1934.
(j) Thorand, S.; Krause, N. J. Org. Chem. 1998, 63, 8551. (k) Mori, A.;
Kawashima, J.; Shimada, T.; Suguro, M.; Hirabayashi, K.; Nishihara, Y.
Org. Lett. 2000, 2, 2935. (l) Castanet, A.; Colobert, F.; Schlama, T. Org. Lett.
2000, 2, 3559. (m) Consorti, C. S.; Flores, F. R.; Rominger, F.; Dupont, J.
Adv. Synth. Catal. 2006, 348, 133. (n) Monnier, F.; Turtaut, F.; Duroure, L.;
Taillefer, M. Org. Lett. 2008, 10, 3203.
(9) (a) Radhakrishnan, U.; Stang, P. J. Org. Lett. 2001, 3, 895.
(b) Anastasia, L.; Negishi, E.-i. Org. Lett. 2001, 3, 3111. (c) Eckert, T.;
Ipaktschi, J. Synth. Commun. 1998, 28, 327.
(10) For selected papers on Ag salt-promoted organic reactions, see:
~
ꢀ
(a) Moreno-Manas, M.; Perez, M.; Pleixats, R. J. Org. Chem. 1996, 61,
2346. (b) Zou, G.; Reddy, Y. K.; Falck, J. R. Tetrahedron Lett. 2001, 42,
7213. (c) Satoh, T.; Ogino, S.; Miura, M.; Nomura, M. Angew. Chem., Int.
Ed. 2004, 43, 5063. (d) Nishihara, Y.; Onodera, H.; Osakada, K. Chem.
Commun. 2004, 192. (e) Letinois-Halbes, U.; Pale, P.; Berger, S. J. Org.
Chem. 2005, 70, 9185.
(6) Zou, G.; Zhu, J.; Tang, J. Tetrahedron Lett. 2003, 44, 8709.
(7) Yang, F.; Wu, Y. Eur. J. Org. Chem. 2007, 3476.
(8) For a paper on CuI-catalyzed cross-coupling of arylboronic acids with
terminal alkynes, see: Pan, C.; Luo, F.; Wang, W.; Ye, Z.; Cheng, J.
Tetrahedron Lett. 2009, 50, 5044.
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SCHEME 2. Controlled Experiments: The Traditional Sonongashira Reaction of N-Methyl-N-phenylpropiolamide with Aryl Iodides
TABLE 1. Screening Optimal Conditionsa
entry
[Pd] (mol %)
[Ag] (mol %)
base (equiv)
solvent
T (°C)
yield (%)
1
2
3
Pd(OAc)2 (0.1)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.0001)
Ag2O (1)
Ag2O (1)
Ag2O (2)
Ag2O (1.5)
Ag2O (0.5)
CH3ONa (1)
CH3ONa (1)
CH3ONa (1)
CH3ONa (1)
CH3ONa (1)
CH3ONa (1)
CH3ONa (2)
K2CO3 (2)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
n-PrCN
toluene
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
100
100
100
100
100
100
100
100
100
100
100
100
100
100
70
50
rt
70
70
70
70
70
61
60
75
75
40
trace
63
85
53
65
72
63
61
72
88
84
72
72
0
4
5b
6
7
8
9
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
Ag2O (1.5)
AgNO3 (1.5)
AgOAc (1.5)
AgBF4 (1.5)
Ag2CO3 (3.5)
Na2CO3 (2)
Cs2CO3 (2)
KOAc (2)
10
11
12
13
14
15
16
17c
18c
19
20
21d
22
23
24
25
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
PdCl2 (0.01)
PdCl2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
Pd(OAc)2 (0.01)
80
76
66
71
67
67
70
70
70
aReaction conditions: 1a (0.3 mmol), 2a (0.36 mmol), base, and solvent (2 mL) at 100 °C for 12 h. bFor 16 h. cFor 48 h. ddppf (0.02 mol %) was added.
the reaction with substrate 1a, Pd(OAc)2 (0.01 mol %), and
Ag2O (1.5 equiv), and the yields were affected by the steric
hindrance in the order 2b (90%) > 2c (86%) > 2d (75%)
(entries 1-3). Interestingly, only boronic acid group in
substrate 2h could react with alkyne 2a, and the active iodo
group was inert under the optimal conditions: this provides
an attractive route to introduction of new functional groups
in this skeleton (entry 7). We were pleased that substrates 2i
and 2l, with an active formylaryl or vinylaryl group, were
tolerated well (entries 8 and 11). Notably, (E)-prop-1-enyl-
boronic acid (2m) was suitable for the reaction under the
optimal conditions (90%, entry 12). Interestingly, two other
boronic electrophiles, phenylboronic acid pinacol ester (2n)
and PhBF3K (2o), were also compatible under the standard
conditions (entries 13 and 14). Subsequently, a number of
electron-poor alkynes, either amide or ester, were examined
in the presence of phenylboronic acid (2a), Pd(OAc)2 (0.01
mol %), and Ag2O (1.5 equiv) (entries 15-22). We found
that N,N-disubstituted amides 1b-f were successfully re-
acted with phenylboronic acid (2a) in moderate to good
yields (entries 15-19), but N-acetyl-N-phenylamide 1g has
no activity under the same conditions (entry 20). Unfortu-
nately, monosubstituted amide 1h was also inert for the
reaction (entry 21). Ester 1i was tested, and 71% yield was
obtained by reacting with phenylboronic acid (2a), Pd(OAc)2,
and Ag2O (entry 22). However, propiolic acid (1j) has no
activity for the reaction under the same conditions (entry 23).
It is noteworthy that ynone (1k) can smoothly undergo the
reaction with boronic acid (2k), Pd(OAc)2, and Ag2O in 54%
yield (entry 24).9
As shown in Scheme 3, a number of aromatic and aliphatic
alkynes were initially investigated under standard condi-
tions. In the presence of Pd(OAc)2 (0.01 mol %), Ag2O
(1.5 equiv), K2CO3 (2 equiv), and MeCN (2 mL), phenyla-
cetylene (1j) was a suitable substrate for the reaction with
phenylboronic acid (2a), providing the desired product 27
in 74%. However, the reaction of ethynyltrimethylsilane
with p-tolylboronic acid (2b) was unsuccessful (28). To our
delight, aliphatic alkynes, bearing a tert-butyl, n-pentyl, or
cyclopropyl group, were consistent with the standard condi-
tions (29-31). Although the yields were not satisfactory
from the reactions of amides 1 with 2-formylphenylboronic
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TABLE 2. The Sonogashira Cross-coupling Reactions of Electron-Poor Terminal Alkynes (1) with Boronic Acids (2) in the Presence of Pd(OAc)2
and Ag2Oa
aReaction conditions: 1 (0.3 mmol), 2 (0.36 mmol), Pd(OAc)2 (0.01 mol %), Ag2O (1.5 equiv), K2CO3 (2 equiv), and MeCN (2 mL) at 70 °C for 12 h.
bPd(OAc)2 (3 mol %).
acid (2i) in the presence of MeOH, two interesting tandem
1H-isochromene products 32 and 33 were obtained in
one pot.11
reactions of iodo-containing products with phenylacetylene
were carried out using our previously reported Pd(OAc)2/
DABCO catalytic system,5b,12 providing the target diynes in
excellent yields.
A possible mechanism as outlined in Scheme 5 was
proposed.6-8,10 Initially, the reaction between Pd(II) and
alkynylsilver or alkyne with the aid of base affords inter-
mediate A. Transmetalation of intermediate A with aryl-
boronic acid 2 subsequently takes place leading to inter-
mediate B. Finally, reductive elimination of intermediate B
gives the desired product and Pd(0) species. Pd(0) species can
The above results showed that the iodo group was inert
under the optimal conditions (entry 7 in Table 2). Thus, this
novel methodology was applied to the one-pot synthesis of
diynes through a dual Sonogashira cross-coupling process
(Scheme 4). Treatment of 4-iodophenylboronic acid (2h)
with amides (1a and 1f) or ester (1i), Pd(OAc)2 (0.01 mol %),
and Ag2O (1.5 equiv) first afforded the corresponding
iodo-containing products in good yields. Subsequently, the
(11) Chandra, A.; Singh, B.; Khanna, R. S.; Singh, R. M. J. Org. Chem.
2009, 74, 5664.
(12) (a) Li, J.-H.; Zhang, X.-D.; Xie, Y.-X. Synthesis 2005, 804.
(b) Luque, R.; Macquarrie, D. J. Org, Biomol. Chem. 2009, 7, 1627.
5638 J. Org. Chem. Vol. 75, No. 16, 2010

Zhou et al.
JOCArticle
SCHEME 3. Reactions of Other Substrates
SCHEME 4. Synthesis of Diynesa
aReaction conditions: (i) 1 (0.3 mmol), 2h (0.36 mmol), Pd(OAc)2 (0.01 mol %), Ag2O (1.5 equiv), K2CO3 (2 equiv) and MeCN (2 mL) at 70 °C for 12 h;
(ii) Phenylacetylene (1.5 equiv), Pd(OAc)2 (0.001 mol %), DABCO (3 equiv), and MeCN (2 mL) at room temperature for 24 h.
SCHEME 5. Possible Mechanism
be readily oxidized by Ag2O to the active Pd(II) species.
Therefore, we deduce at least four roles that Ag2O plays in
the reaction, including the following: (1) base, (2) the reac-
tion partner for the generation of the active alkynylsilver in
situ, (3) promoter for the activation of the alkynylpalladium
complex A facilitating the transmetalation of aryl group
from arylboronic acid, and (4) oxidant to regenerate the
active Pd(II) species.
For the synthesis of 1H-isochromenes, a possible step was
described according to the reported mechanism:11 the corre-
sponding 2-ethynylbenzaldehydes were first generated from
the reaction of amides 1 with 2-formylphenylboronic acid (2i),
J. Org. Chem. Vol. 75, No. 16, 2010 5639

Zhou et al.
JOCArticle
and then nucleophilic addition of MeOH to 2-ethynylbenzal-
dehydes readily took place leading to the target products.
In summary, we have developed a palladium-catalyzed
cross-coupling protocol for selectively preparing internal
alkynes. In the presence of Pd(OAc)2 and Ag2O, a variety
of terminal alkynes, particularly electron-poor terminal
alkynes, smoothly underwent the reaction with numerous
boronic acids to afford the corresponding internal alkynes in
moderate to good yields. In comparison with the previously
reported results, several features were established: (1) this
reaction is general; (2) this reaction is carried out under a
relative lower loading Pd conditions: the maximal TONs of
the reaction are up to 720,000; and (3) the reaction was
applied to the synthesis of 1H-isochromenes and diynes.
91.2, 82.1, 36.3, 21.5; IR (KBr, cm-1): 2231, 1634, 1589; LRMS
(EI, 70 eV) m/z 249 (Mþ, 38), 143 (100), 40 (48).
N-Methyl-N-phenyl-3-o-tolylpropiolamide (9):4 colorless oil;
1H NMR (500 MHz, CDCl3) δ 7.43 (t, J = 7.0 Hz 2H), 7.36 (t,
J = 8.0 Hz 3H), 7.24-7.20 (m, 2H), 7.06 (t, J = 7.5 Hz,
2H), 3.38 (s, 3H), 1.92 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
154.4, 143.3, 141.1 133.1, 129.8, 129.4, 129.3,128.0, 127.5,
125.5, 120.3, 89.8, 86.3, 36.5, 19.9; IR (KBr, cm-1) 2218,
1638, 1581; LRMS (EI, 70 eV) m/z 249 (Mþ, 43), 143 (100),
115 (68).
3-(2,6-Dimethylphenyl)-N-methyl-N-phenylpropiolamide (10):4
white solid; mp 95.4-96.7 °C (uncorrected); 1H NMR (500 MHz,
CDCl3) δ 7.41 (t, J = 8.0 Hz, 2H), 7.34 (d, J = 7.5 Hz, 3H), 7.09
(t, J = 7.5 Hz, 1H), 6.92 (d, J = 7.5 Hz, 2H), 3.38 (s, 3H), 2.06 (s,
6H); 13C NMR (125 MHz, CDCl3) δ 154.5, 143.4, 141.9, 129.4,
129.3, 128.0, 127.6, 126.6, 120.4, 90.7, 88.7, 36.6, 20.5; IR (KBr,
cm-1) 2204, 1634, 1593; LRMS (EI, 70 eV) m/z 263 (Mþ, 22), 157
(100), 128 (40).
Experimental Section
Typical Experimental Procedure for the Pd(OAc)2-Catalyzed
Cross-Coupling Reaction. Alkyne 1 (0.3 mmol), boronic acid 2
(0.36 mmol), Pd(OAc)2 (0.01 mol %), Ag2O (1.5 equiv), K2CO3
(2 equiv), and MeCN (2 mL) were added to a Schlenk tube in
turn. Then the solution was stirred at 70 °C for the indicated
time (12 h) until complete consumption of starting material as
monitored by TLC and GC-MS analysis. After the reaction
was finished, the mixture was filtered, extracted with ethyl
acetate, and evaporated in vacuum. The residue was purified
by flash column chromatography on silica gel (hexane/ethyl
acetate) to afford the desired product.
3-(4-Fluorophenyl)-N-methyl-N-phenylpropiolamide (11):4
white solid; mp 50.3-51.6 °C (uncorrected); 1H NMR (500
MHz, CDCl3) δ 7.46 (t, J = 7.5 Hz, 2H), 7.41-7.35 (m, 3H),
7.13-7.10 (m, 2H), 6.93 (t, J = 8.5 Hz, 2H), 3.40 (s, 3H); 13
C
NMR (125 MHz, CDCl3) δ 164.3, 162.3, 154.1, 143.1, 134.5,
134.5, 129.1, 128.0, 127.4, 115.8, 115.6, 89.7, 82.3, 36.3; IR
(KBr, cm-1): 2231, 1638, 1597; LRMS (EI, 70 eV) m/z 253
(Mþ, 49), 147 (100).
3-(4-Iodophenyl)-N-methyl-N-phenylpropiolamide (12):4 white
solid, 54.1-55.6 °C (uncorrected);1H NMR(500 MHz, CDCl3) δ
7.58 (d, J = 8.5 Hz, 2H), 7.45 (t, J = 7.5 Hz, 2H), 7.40-7.34 (m,
3H), 6.83 (d, J = 7.5 Hz, 2H), 3.39 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 154.0, 143.1, 137.6, 133.6, 129.1, 128.0, 127.4, 119.8,
96.5, 89.7, 83.7, 36.3; IR (KBr, cm-1) 2218, 1646, 1593; LRMS
(EI, 70 eV) m/z 361 (Mþ, 64), 255 (100), 128 (46).
N-Methyl-N,3-diphenylpropiolamide (4):4 white solid; mp
65.2-66.3 °C (uncorrected); 1H NMR (500 MHz, CDCl3) δ
7.45 (t, J = 7.5 Hz, 2H), 7.40-7.38 (m, 1H), 7.36 (d, J = 7.5 Hz,
2H), 7.34-7.30 (m, 1H), 7.27-7.22 (m, 2H), 7.13 (d, J = 8.0 Hz,
2H), 3.39 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 154.3, 143.2,
132.4, 129.9, 129.1, 128.2, 127.9, 127.3, 120.3, 90.8, 82.5, 36.3;
IR (KBr, cm-1) 2207, 1634; LRMS (EI, 70 eV) m/z 235 (Mþ, 34),
129 (100).
3-(2-Formylphenyl)-N-methyl-N-phenylpropiolamide (13):
yellow solid; mp 63.2-64.5 °C (uncorrected); 1H NMR (500
MHz, CDCl3) δ 9.36 (s, 1H), 7.82 (d, J = 7.0 Hz, 1H), 7.54-
7.45 (m, 6H), 7.37-7.35 (m, 2H), 3.41 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 190.5, 153.6, 142.7, 136.8, 134.2, 133.6,
130.3, 129.5, 128.5, 127.4, 126.9, 123.6, 88.4, 85.9, 36.5; IR
(KBr, cm-1): 2214, 1699, 1634, 1593; LRMS (EI, 70 eV) m/z
263 (Mþ, 10), 234 (100), 101 (67); HRMS (EI) for C17H13NO2
(Mþ) calcd 263.0946, found 263.0943.
3-(4-Acetylphenyl)-N-methyl-N-phenylpropiolamide (5):4 pale
yellow solid; mp 92.2-93.9 °C (uncorrected); 1H NMR (500
MHz, CDCl3) δ 7.82 (d, J = 8.5 Hz, 2H), 7.47 (t, J = 7.5 Hz,
2H), 7.41 (t, J = 7.5 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.22 (d,
J = 8.5 Hz, 2H), 3.40 (s, 3H), 2.56 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 197.0, 153.8, 143.0, 137.4, 132.4, 129.2, 128.3, 128.1,
127.3, 125.0, 89.3, 84.8, 36.3, 26.6; IR (KBr, cm-1) 2222, 1681,
1626, 1594; LRMS (EI, 70 eV) m/z 277 (Mþ, 56), 171 (100),
128 (32).
N-Methyl-3-(3-nitrophenyl)-N-phenylpropiolamide (14): yel-
low oil; 1H NMR (500 MHz, CDCl3) δ 8.18-8.16 (m, 1H), 7.90
(s, 1H), 7.51-7.44 (m, 5H), 7.39-7.37 (m, 2H), 3.42 (s, 3H); 13
C
NMR (125 MHz, CDCl3) δ 153.5, 147.9, 142.8, 137.8, 129.6,
129.4, 128.4, 127.4, 127.2, 124.5, 122.2, 87.7, 84.3, 36.4; IR
(KBr, cm-1) 2210, 1638, 1585; LRMS (EI, 70 eV) m/z 280 (Mþ,
99), 174 (83), 128 (100); HRMS (EI) for C16H12N2O3 (Mþ)
calcd 280.0848, found 280.0846.
3-(4-Methoxyphenyl)-N-methyl-N-phenylpropiolamide (6):4
pale yellow solid; mp 93.6-94.9 °C (uncorrected); H NMR
1
(500 MHz, CDCl3) δ 7.45 (t, J = 7.5 Hz, 2H), 7.40-7.35 (m,
3H), 7.07 (d, J = 9.0 Hz, 2H), 6.75 (d, J = 8.5 Hz, 2H), 3.77 (s,
3H), 3.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 160.8, 154.6,
143.3, 134.2, 129.0, 127.8, 127.4 113.9, 112.2, 91.4, 81.9, 55.2,
36.2; IR (KBr, cm-1) 2210, 1636, 1593; LRMS (EI, 70 eV) m/z
265 (Mþ, 33), 159 (100).
N-Methyl-N-phenyl-3-(4-vinylphenyl)propiolamide (15): color-
less oil; 1H NMR (500 MHz, CDCl3) δ 7.47-7.35 (m, 5H),
7.30-7.26 (m, 2H), 7.09 (d, J = 8.0 Hz, 2H), 6.66-6.60 (m, 1H),
5.74 (d, J = 17.5 Hz, 1H), 5.30 (d, J = 11.0 Hz, 1H), 3.39 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 154.3, 143.2, 139.0, 135.8, 132.6,
129.1, 127.9, 127.2, 126.0, 119.4, 115.8, 90.8, 83.1, 36.3; IR (KBr,
cm-1) 2216, 1642, 1493; LRMS (EI, 70 eV) m/z 261 (Mþ, 4), 253
(49), 147 (100); HRMS (EI) for C18H15NO (Mþ) calcd 261.1154,
found 261.1151.
3-(2-Methoxyphenyl)-N-methyl-N-phenylpropiolamide (7):4
pale yellow solid; mp 86.3-87.8 °C (uncorrected); H NMR
1
(500 MHz, CDCl3) δ 7.45-7.35 (m, 5H), 7.29 (d, J = 8.5 Hz,
1H), 7.10 (d, J = 7.5 Hz, 1H), 6.82-6.75 (m, 2H), 3.69 (s, 3H),
3.39 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 161.0, 154.4,
143.2, 134.4, 131.5, 129.0, 127.5, 127.3, 120.2, 110.6, 109.7,
87.7, 86.4, 55.4, 36.4; IR (KBr, cm-1) 2210, 1638, 1581; LRMS
(EI, 70 eV) m/z 265 (Mþ, 9), 159 (72), 147 (52), 131 (44), 115
(100).
(E)-N-Methyl-N-phenylhex-4-en-2-ynamide (16): colorless
oil; H NMR (500 MHz, CDCl3) δ 7.41 (t, J = 7.5 Hz, 2H),
1
7.34 (t, J = 7.5 Hz, 1H), 7.28 (d, J = 8.0 Hz, 2H), 6.05-5.98
(m, 1H), 5.36-5.30 (m, 1H), 3.34 (s, 3H), 1.72 (d, J = 6.5 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 154.4, 145.2, 143.1, 129.0,
127.6, 127.1, 108.9, 90.2, 81.0, 36.3, 18.9; IR (KBr, cm-1):
2202, 1626, 1593, 1495; LRMS (EI, 70 eV) m/z 199 (Mþ, 16),
198 (29), 184 (70), 93(100); HRMS (EI) for C13H13NO (Mþ)
calcd 199.0997, found 199.0995.
N-Methyl-N-phenyl-3-p-tolylpropiolamide (8):4 pale yellow
solid;mp 84.0-85.3 °C (uncorrected); 1H NMR (500 MHz,
CDCl3) δ 7.44 (t, J = 7.5 Hz, 2H), 7.40-7.35 (m, 3H), 7.03 (s,
4H), 3.39 (s, 3H), 2.30 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
154.4, 143.2, 140.4, 132.3, 129.0, 129.0, 127.8, 127.3, 117.2,
5640 J. Org. Chem. Vol. 75, No. 16, 2010

Zhou et al.
JOCArticle
N-(4-Methoxyphenyl)-N-methyl-3-phenylpropiolamide (17):4
yellow solid; mp 78.4-79.7 °C (uncorrected); H NMR (500
27.9, 21.4; LRMS (EI, 70 eV) m/z 172 (Mþ, 40),157 (100),
142 (44).
1
MHz, CDCl3) δ 7.34-7.31 (m, 1H), 7.28-7.23 (m, 4H), 7.18 (d,
J = 8.0 Hz, 2H), 6.95 (d, J = 7.5 Hz, 2H), 3.85 (s, 3H), 3.35 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 159.0, 154.5, 136.0, 132.3,
130.1, 128.5, 128.2, 120.4, 114.2, 90.8, 82.5, 55.5, 36.5; IR (KBr,
cm-1) 2218, 1638, 1507; LRMS (EI, 70 eV) m/z 265 (Mþ, 34),
159 (100).
1-(Hept-1-ynyl)-4-methylbenzene (30):7 colorless oil; 1H
NMR (500 MHz, CDCl3) δ 7.28 (d, J = 8.0 Hz, 2H), 7.07 (d,
J = 8.0 Hz, 2H), 2.38 (t, J = 7.5 Hz, 2H), 2.31 (s, 3H), 1.60 (t,
J = 7.5 Hz, 2H), 1.44-1.41 (m, 4H), 0.92 (t, J = 7.5 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ 137.3, 131.4, 128.9, 121.0, 89.6,
80.5, 31.1, 28.5, 22.2, 21.3, 19.4, 14.0; LRMS (EI, 70 eV) m/z 186
(Mþ, 33),157 (33), 142 (38), 131(69), 129 (100).
N-Benzyl-N,3-diphenylpropiolamide (18):4 pale yellow solid;
mp 84.2-85.7 °C (uncorrected); 1H NMR (500 MHz, CDCl3) δ
1-(Cyclopropylethynyl)-4-methylbenzene (31):17 colorless oil;
1H NMR (500 MHz, CDCl3) δ 7.18 (d, J = 8.0 Hz, 2H), 6.97 (d,
J = 8.0 Hz, 2H), 2.23 (s, 3H), 1.37-1.32 (m, 1H), 0.76-0.74 (m,
2H), 0.71-0.70 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 137.3,
131.4, 128.9, 120.8, 92.5, 75.8, 21.3, 8.5, 0.1; LRMS (EI, 70 eV)
m/z 130 (Mþ, 100), 115 (65), 74 (53).
7.36-7.15 (m, 13H), 7.09 (d, J = 8.0 Hz, 2H), 5.00 (s, 2H); 13
C
NMR (125 MHz, CDCl3) δ 154.4, 141.6, 136.6, 132.4, 129.9,
128.9, 128.7, 128.6, 128.4, 128.2, 128.1, 127.5, 120.3, 91.4, 82.5,
52.2; IR (KBr, cm-1) 2216, 1634, 1589; LRMS (EI, 70 eV) m/z
311 (Mþ, 39), 129 (100), 91 (44).
N-Allyl-N,3-diphenylpropiolamide (19): white solid; mp
66.3-67.6 °C (uncorrected); H NMR (500 MHz, CDCl3) δ
3-(4-Iodophenyl)-1-morpholinoprop-2-yn-1-one (35): white so-
lid; mp 154.6-155.8 °C (uncorrected); 1H NMR (500 MHz,
CDCl3) δ 7.73-7.72 (m, 2H), 7.26-7.24 (m, 2H), 3.83-3.81 (m,
2H), 3.76-3.74 (m, 2H), 3.70 (s, 4H); 13C NMR (125 MHz,
CDCl3) δ 152.9, 137.8, 133.6, 119.6, 96.8, 90.2, 81.8, 66.8, 66.4,
47.3, 42.0; IR (KBr, cm-1) 2210, 1625; LRMS (EI, 70 eV) m/z
341 (Mþ, 73), 254 (100), 128 (80); HRMS (EI) for C13H12INO2
(Mþ) calcd 340.9913, found 340.9910.
1
7.43-7.39 (m, 3H), 7.33 (t, J = 7.5 Hz, 3H), 7.22 (t, J = 7.5 Hz,
2H), 7.11 (d, J = 8.0 Hz, 2H), 5.92-5.87 (m, 1H), 5.19-5.15
(m, 2H), 4.42 (d, J = 6.0 Hz, 2H); 13C NMR (125 MHz, CDCl3)
δ 154.0, 141.8, 132.4, 132.3, 129.9, 129.0, 128.4, 120.4, 118.3,
91.0, 82.6, 51.3; IR (KBr, cm-1) 2221, 1628; LRMS (EI, 70 eV)
m/z 261 (Mþ, 14), 232 (19), 129 (100); HRMS (EI) for
C18H15NO (Mþ) calcd 261.1154, found 261.1150.
Ethyl 3-(4-iodophenyl)propiolate (37):15 colorless oil; 1H
NMR (500 MHz, CDCl3) δ 7.73 (d, J = 7.0 Hz, 2H), 7.29 (d,
J = 7.0 Hz, 2H), 4.32-4.28 (m, 3H), 1.35 (t, J = 7.5 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ: 153.8, 137.9, 134.1, 119.1, 97.4,
84.9, 81.8, 62.2, 14.0; IR (KBr, cm-1) 2210, 1712; LRMS (EI, 70
eV) m/z 300 (Mþ, 28), 255 (45), 228 (100).
Typical Experimental Procedure for the Synthesis of 1H-
Isochromenes. Alkyne 1 (0.3 mmol), boronic acid 2 (0.36 mmol),
Pd(OAc)2 (0.01 mol %), Ag2O (1.5 equiv), K2CO3 (2 equiv),
MeCN (2 mL), and MeOH (4 mL) were added to a Schlenk tube
in turn. Then the solution was stirred at 70 °C for the indicated
time (24 h) until complete consumption of starting material as
monitored by TLC and GC-MS analysis. After the reaction
was finished, the mixture was filtered, extracted with ethyl
acetate, and evaporated in vacuum. The residue was purified
by flash column chromatography on silica gel (hexane/ethyl
acetate) to afford the desired product.
N,N-Diethyl-3-phenylpropiolamide (20):13 colorless oil; 1H
NMR (500 MHz, CDCl3) δ 7.54 (d, J = 7.5 Hz, 2H), 7.41 (t,
J = 7.5 Hz, 1H), 7.36 (t, J = 7.5 Hz, 2H), 3.69-3.65 (m, 2H),
3.50-3.46 (m, 2H), 1.28 (t, J = 7.5 Hz, 2H), 1.18 (t, J = 7.5 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ: 153.9, 132.2, 129.8, 128.4,
120.7, 88.9, 81.8, 43.5, 39.2, 14.3, 12.8; IR (KBr, cm-1): 2213,
1636; LRMS (EI, 70 eV) m/z 201 (Mþ, 31), 129 (100).
1-Morpholino-3-phenylprop-2-yn-1-one (21):14 colorless oil;
1H NMR (500 MHz, CDCl3) δ 7.55 (d, J = 7.5 Hz, 2H), 7.43
(m, 1H), 7.37 (t, J = 7.5 Hz, 2H), 3.85 (t, J = 5.0 Hz 2H), 3.76 (t,
J = 5.0 Hz, 2H), 3.71 (s, 4H); 13C NMR (125 MHz, CDCl3)
δ 153.1, 132.3, 130.1, 128.5, 120.1, 91.2, 80.6, 66.8, 66.4, 47.2,
41.9; IR (KBr, cm-1) 2218, 1626; LRMS (EI, 70 eV) m/z 215
(Mþ, 29), 129 (100).
Ethyl 3-phenylpropiolate (24):14 yellow oil; 1H NMR (500
MHz, CDCl3) δ 7.59 (d, J = 7.5 Hz, 2H), 7.47-7.43 (m, 1H),
7.38 (t, J = 7.5 Hz, 2H), 4.32-4.28 (m, 2H), 1.36 (t, J = 7.0 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 154.1, 133.0, 130.6, 128.5,
120.0, 86.0, 80.7, 62.1, 14.1; IR (KBr, cm-1) 2210, 1709; LRMS
(EI, 70 eV) m/z 174 (Mþ, 15), 129 (100), 102 (87).
1-Methoxy-N-methyl-N-phenyl-1H-isochromene-3-carboxa-
mide (32): yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.45-7.39
(m, 4H), 7.35-7.31 (m, 2H), 7.28 (d, J = 7.5 Hz, 1H), 7.17 (d,
J = 7.5 Hz, 1H), 6.51 (s, 1H), 5.37 (s, 1H), 3.60 (s, 3H), 3.38 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 165.3, 161.4, 144.6, 138.6,
134.3, 130.7, 129.9, 129.4, 127.3, 127.1, 123.1, 120.7, 108.6,
89.1, 55.9, 36.9; IR (KBr, cm-1) 1663; LRMS (EI, 70 eV) m/z
295 (Mþ, 3), 263 (66), 189 (100), 145 (89); HRMS (EI) for
3-(3-Nitrophenyl)-1-phenylprop-2-yn-1-one (26):15 white so-
1
lid; mp 142.0-143.6 °C (uncorrected); H NMR (500 MHz) δ
8.53 (s, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.22 (d, J = 7.5 Hz, 2H),
8.00 (s, d, J = 7.5 Hz, 1H), 7.70-7.64 (m, 2H), 7.56 (t, J = 7.5
Hz, 2H); 13C NMR (125 MHz) δ 177.4, 148.2, 138.4, 136.4,
134.6, 129.9, 129.6, 128.8, 127.6, 125.2, 122.0, 89.0, 88.0; IR
(KBr, cm-1) 2208, 1634; LRMS (EI, 70 eV) m/z 251 (Mþ, 73),
223 (100), 176 (53), 177 (31), 128 (45), 77 (49).
C
18H17NO3 (Mþ) calcd. 295.1208, found 295.1204.
N-Benzyl-1-methoxy-N-phenyl-1H-isochromene-3-carboxamide
1
(33). yellow oil; H NMR (500 MHz, CDCl3) δ 7.44-7.42 (m,
2H), 7.34-7.21 (m, 9H), 7.12 (t, J = 8.5Hz, 3H), 6.53 (s, 1H), 5.34
(s, 1H), 5.15 (d, J = 7.5 Hz, 1H), 4.89 (d, J = 7.5 Hz, 1H), 3.61 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 165.1, 161.9, 143.1, 138.7,
138.1, 134.3, 130.8, 129.9, 129.2, 128.7, 128.3, 128.3, 127.3, 127.0,
123.1, 120.7, 108.7, 88.9, 55.9, 52.5; IR (KBr, cm-1) 1665; LRMS
(EI, 70 eV) m/z 371 (Mþ, 4), 339 (59), 189 (100), 145 (76); HRMS
(EI) for C24H21NO3 (Mþ) calcd 371.1521, found 371.1518.
Typical Experimental Procedure for the Pd(OAc)2-Catalyzed
Sonogashira Cross-Coupling Reaction of Aryl Iodides:5b Iodo-
phenylproiolamides 12, 35, or 37 (0.3 mmol), phenylacetylene 1j
(0.45 mmol), Pd(OAc)2 (0.001 mol %), DABCO (3 equiv), and
MeCN (2 mL) were added to a Schlenk tube in turn. Then the
solution was stirred at room temperature for the indicated time
(24 h) until complete consumption of starting material as
monitored by TLC and GC-MS analysis. After the reaction
1,2-Diphenylethyne (27):4 white solid; mp 59.4-60.3 °C
1
(uncorrected); H NMR (500 MHz, CDCl3) δ 7.54-7.52 (m,
4H), 7.37-7.32 (m, 6H); 13C NMR (125 MHz, CDCl3) δ 131.6,
128.3, 128.2, 123.3, 89.4; IR (KBr, cm-1) 2216; LRMS (EI, 70
eV) m/z 178 (Mþ, 100).
1-(3,3-Dimethylbut-1-ynyl)-4-methylbenzene (28):16 colorless
1
oil; H NMR (500 MHz, CDCl3) δ 7.20 (d, J = 9.0 Hz, 2H),
7.00 (d, J = 7.0 Hz, 2H), 2.25 (s, 3H), 1.24 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 137.3, 131.4, 128.8, 121.0, 97.7, 79.0, 31.1,
(13) Kamijo, S.; Kanazawa, C.; Yamamoto, Y. J. Am. Chem. Soc. 2005,
127, 9260.
ꢁ
(14) Kramer, S.; Dooleweerdt, K.; Lindhardt, A. T.; Rottlander, M.;
Skrydstrup, T. Org. Lett. 2009, 11, 4208.
(15) Savechenkov, P. Y.; Rudenko, A. P.; Vasilev, A. V.; Fukin, G. K.
ꢀ
Russ. J. Org. Chem. 2005, 41, 1316.
(16) Vogel, P.; Dubbaka, S.-R. Adv. Synth. Catal. 2004, 346, 1793.
(17) Ye, S.-Y.; Yu, Z.-X. Org. Lett. 2004, 12, 804.
J. Org. Chem. Vol. 75, No. 16, 2010 5641

Zhou et al.
JOCArticle
was finished, the mixture was filtered, extracted with ethyl
acetate, and evaporated in vacuum. The residue was purified
by flash column chromatography on silica gel (hexane/ethyl
acetate) to afford the desired product.
N-Methyl-N-phenyl-3-(4-(phenylethynyl)phenyl)propiolamide
(34): white solid; mp 102.4.5-103.6 °C (uncorrected); 1H NMR
(500 MHz, CDCl3) δ 7.55-7.44 (m, 4H), 7.41-7.34 (m, 8H),
7.11 (d, J = 7.5 Hz, 2H), 3.40 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 154.1, 143.1, 132.3, 131.6, 131.4, 129.2, 128.7, 128.4,
128.0, 127.4, 125.0, 122.7, 120.0, 92.1, 90.3, 88.6, 84.0, 36.4; IR
(KBr, cm-1) 2214, 1621; LRMS (EI, 70 eV) m/z 335 (Mþ, 46),
229 (100), 200 (21); HRMS (EI) for C24H17NO (Mþ) calcd
335.1310, found 335.1312.
1-Morpholino-3-(4-(phenylethynyl)phenyl)prop-2-yn-1-one (36):
white solid; mp 146.8-147.5 °C (uncorrected); H NMR (500
MHz, CDCl3) δ 7.54-7.52 (m, 6H), 7.36 (t, J = 3.5 Hz, 3H), 3.84
(t, J = 5.0 Hz, 2H), 3.76 (t, J = 5.0 Hz, 2H), 3.71(s, 4H); 13C
NMR (125 MHz, CDCl3) δ: 153.0, 132.3, 131.7, 131.6, 128.7,
128.4, 125.3, 122.6, 119.8, 92.4, 90.7, 88.5, 82.1, 66.9, 66.5, 47.3,
42.0; IR (KBr, cm-1): 2197, 1617; LRMS (EI, 70 eV) m/z 315
(Mþ, 61), 229 (100), 200 (30); HRMS (EI) for C21H17NO2 (Mþ)
calcd 315.1259, found 315.1257.
Ethyl 3-(4-(phenylethynyl)phenyl)propiolate (38): white solid;
mp 99.5-100.6 °C (uncorrected); 1H NMR (500 MHz, CDCl3)
δ: 7.56-7.50 (m, 6H), 7.36 (t, J = 3.5 Hz, 2H), 4.32-4.28 (m,
2H), 1.36 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
153.9, 132.8, 131.6, 131.6, 128.7, 128.4, 125.7, 122.6, 119.1, 92.5,
88.5, 85.4, 82.0, 62.1, 14.0; IR (KBr, cm-1) 2206, 1703; LRMS
(EI, 70 eV) m/z 274 (Mþ, 47), 229 (31), 202 (100); HRMS (EI) for
C19H14O2 (Mþ) calcd 274.0994, found 274.0991.
Acknowledgment. We thank the Scientific Research Fund
of Hunan Provincial Education Department (No. 08A037)
and the National Natural Science Foundation of China (No.
20872112) for financial support.
1
Supporting Information Available: Copies of spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
5642 J. Org. Chem. Vol. 75, No. 16, 2010