One-pot synthesis of propynoates and propynenitriles

Article abstract of DOI:10.1139/cjc-2016-0181

An efficient transformation towards propynoates and propynenitriles is herein described. The practical methodology was conducted at low temperature (-78 or -60 °C) in a one-pot manner with the assistance of base rather than any transition metal catalysts. The base-induced protocol exhibits good functional group tolerance (up to 28 examples) and high efficiency (up to 92% yields) towards substituted acetylenes of great synthetic significance, which was also well demonstrated by the gram-scale reactions.

Full text of DOI:10.1139/cjc-2016-0181

Page 1 of 8
One-pot Synthesis of Propynoates and Propynenitriles
Fan Shu, Qingjuan Zheng, Wanrong Dong,* Zhihong Peng* and Delie An*
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering,
Hunan University, Changsha 410082, P. R. China.
Emails: wanrongdong@hnu.edu.cn, pzh7251@hnu.edu.cn, deliean@hnu.edu.cn
An efficient transformation towards propynoates and propynenitriles was herein described. The practical method-
o
ology was conducted at low temperature (-78 or -60 C) in a one-pot manner with assistance of base rather than
any transition metal catalysts. The base-induced protocol exhibits good functional groups tolerance (up to 28 ex-
amples) and high efficiency (up to 92% yields) towards substituted acetylenes of great synthetic significance, which
was also well-demonstrated by the gram-scale reactions.
Keywords: Propynoates, Propynenitriles, One-pot Preparation, Base-induced, Elimination
Introduction
Results and Discussion
Propynoates and propynenitriles[1] have attracted
widespread attention for their distinguished photocon-
ductive or biological properties,[2] as well their roles as
the pivotal intermediates for the construction of cyclic
compounds in the synthetic and pharmaceutical chemis-
try.[3] Therefore, great efforts have been devoted for the
synthesis of these compounds. Usually, coupling reac-
tions mediated by transition metal catalysts such as Cu,
Pd and Fe were generally utilized for the synthesis of
the versatile molecules. Some unsaturated compounds
like acetylenes,[4] acetylenic bromides,[5] arylpropiolic
acids,[6] 1,1-dihalo-1-alkenes[7] and others.[8] were usu-
ally employed for the coupling with suitable partners.
However, homo-coupling of the alkynyl substrates was
unavoidable in the metallic catalysis. Thus, attempts
have been devoted to seek the possibility of efficiently
forming propynoates and propynenitriles without the
involvement of any transition metal catalysts. Research
work has been widely carried out for the construction of
triple bonds from the substrates of different structure.
Pioneered by Negishi[9] and Otera,[10] the topic has
gained tremendous development thus far. For example,
Tajima et al. reported a practical preparation of
propynoates in the presence of KF.[11] While synthesis
of propynenitriles was also realized with assistance of
pyridinium salts from the substrates of similar struc-
ture.[12] As a long-standing interest of our group is
aimed at the synthesis of heteroatom-substituted alkynes
(S, Se, N or P),[13] we plan to extend the general and
practical methodology for the preparation of propyno-
ates and propynenitriles with electron-deficient car-
bon-carbon triple bonds herein from easily-prepared
starting materials.
To obtain the optimal conditions, reactions with me-
thyl 3-phenyl-3-oxopropanoate (1a) as the model sub-
strate were conducted as summarized in Table 1.
Table 1 Optimization of reaction conditions[a]
Entry
Base
n-BuLi
Solvent Yield (%)[b]
1
2
THF
THF
THF
THF
Et2O
THF
THF
n.d.[c]
LDA
25
3
LiHMDS
KHMDS
84
4
79
5
6[d]
7[d]
LiHMDS
LiHMDS (t-BuOK)
t-BuOK
65
68
trace
aReaction conditions: i) 1a (0.30 mmol), base (0.33 mmol) in dry
THF (3.0 mL); ii) ClP(O)(OEt)2 (0.36 mmol) at -78 oC, then at r.t.
c
for 30 min; iii) base (0.45 mmol) at -78 oC. bIsolated yields. n.d.
strands for not detected. dConditions: 1) 1a (0.30 mmol),
LiHMDS (0.33 mmol) or t-BuOK (0.33 mmol) in dry THF (3.0
o
mL); 2) ClP(O)(OEt)2 (0.36 mmol) at -78 C, then at r.t. for 30
min; 3) t-BuOK (0.45 mmol) at r.t.
As the results showed, the suitable base for the one-pot
preparation was LiHMDS (entry 3), which afforded the
desired product methyl 3-phenylpropynoate (2a) in 84%
yield, and was superior to other bases such as n-BuLi
(entry 1) and lithium diisopropyl amide (LDA, entry 2).
It was noteworthy that KHMDS was also able to pro-
vide the desired product but in slightly lower yield, 79%
for entry 4. THF performed better than Et2O for the
transformation, since only 65% yield of 2a was obtained

Page 2 of 8
when reaction was conducted in Et2O (entry 5). Utiliza-
tion of t-BuOK, either for deprotonation step or for
elimination step, led to the formation of 2a smoothly,
but in lower yields (entries 6 and 7).
3
4
2d
2e
4-CH3OC6H4, CH3
91
92
2,5-(CH3O)2C6H3, CH3
5
2f
84
6
2g
2h
2i
4-FC6H4, CH3
4-ClC6H4, CH3
82
83
80
78
80
78
81
80
75
78
88
Now with the optimal conditions established, the scope
and limitations of the substrates for the reaction were
evaluated as summarized in Table 2. Except for methyl
3-phenyl-3-oxopropanoate (1a), substrates containing
electron-rich phenyl groups underwent the elimination
transformation successfully towards the desired alkynyl
products. For example, methyl 3-(4-methylphenyl)-3-
7
8
4-BrC6H4, CH3
4-IC6H4, CH3
9
2j
10
11
12
13
14
15
16
2k
2l
3,4-Cl2C6H3, CH3
4-PhC6H4, CH3
2-Naphthyl, CH3
6-CH3O-2-naphthyl, CH3
2-Furyl, CH3
oxopropanoate
3-(2-methylphenyl)-3-oxopropanoate
(1b),
methyl
methyl
(1c),
2m
2n
2o
2p
2q
3-(4-methoxyphenyl)-3-oxopropanoate (1d), methyl
3-(2,5-dimethoxyphenyl)-3- oxopropanoate (1e) and
methyl 3-(1,3-benzodioxol-5-yl)-3-oxopropanoate (1f)
afforded the corresponding methyl propynoates 2b – 2f
successfully, in up to 92% yields (entries 1 – 5). Mean-
while, substrates bearing halogenated phenyl groups
were well compatible with the basic conditions to pro-
duce methyl propynoates, but exhibiting general lower
efficiency by comparison with the substrates with elec-
tron-rich aryl groups. For example, methyl
2-Thiophenyl, CH3
Ph, CH2CH3
[a] Reaction conditions: i) 1 (0.50 mmol), LiHMDS (1.0 M in
o
THF, 0.55 mmol), dry THF (5.0 mL) at -78 C for 30 min; ii)
ClP(O)(OEt)2 (0.60 mmol) at -78 oC and then at r.t. for 30 min;
o
iii) LiHMDS (1.0 M in THF, 0.75 mmol) at -78 C for 1 h. [b]
3-(4-fluorophenyl)-2-propynoate
3-(4-chlorophenyl)-2-propynoate
(2g),
(2h),
methyl
methyl
Isolated yields.
3-(4-bromophenyl)-2-propynoate (2i) and even methyl
3-(4-iodophenyl)-2-propynoate (2j) were afforded
smoothly under the optimal conditions, in yields ranging
from 78% to 83% (entries 6 – 9). Di-halogenated sub-
Encouraged by the broad substrate scope of the one-pot
preparation towards propiolic acid esters, the applicabil-
ity of the alkynylation method in the synthesis of
2-propynenitriles in the same manner was further ex-
plored as shown in Table 3. Pleasingly, under the similar
conditions but at a relatively higher temperature (-60
oC), 3-phenyl-2-propynenitriles (4a) was obtained in the
strate
1k
led
to
the
methyl
3-(3,4-dichlorophenyl)-2-propynoate (2k) in slightly
lower yield, 80% for entry 10. Moreover, biaryl substi-
tuted substrates was also able to afford the desired
one-pot
preparation
protocol
from
products
3-(4,4’-biphenyl)-2-propynoate
readily.
For
instance,
methyl
methyl
3-oxo-3-phenylpropionitrile (3a) in an excellent yield,
up to 85% (entry 1). Analogously, electron-rich phenyl
groups were firstly evaluated in the transformation.
Both mono- and disubstituted phenyl groups were
well-tolerated
3-oxo-3-(4-methylphenyl)
3-oxo-3-(3-methylphenyl)
3-oxo-3-(2-methylphenyl) propionitrile (3d) and
3-oxo-3-(3,4-dimethoxyphenyl) propionitrile (3e) suc-
cessfully afforded the corresponding electron-rich phe-
nyl groups decorated 2-propynenitriles 4b – 4e in yields
from 82% to 91% (entries 2 – 5). Meanwhile, it is
noteworthy that the properties of the substituents on the
phenyl groups of the substrates did not affect the yields
significantly. And it was observed that halogenated
phenyl groups also exhibited good compatibility in the
transformation. Para- or ortho- halogenated phenyl
groups showed slight influence on the yields of the de-
sired products. For example, 3-oxo-3-(4-chlorophenyl)
propionitrile (3f) and 3-oxo-3-(4-bromophenyl) propi-
onitrile (3h) furnished the desired products in 86% and
85% yields, while 3-(2-chlorophenyl)-2-propynenitriles
(4g) and 3-(2-bromophenyl)-2-propynenitriles (4i) were
obtained in 90% yield (entries 6 – 9). In the same man-
(2l),
3-(naphthalene-2-yl)-2-propynoate (2m) and methyl
3-(6-methoxynaphthalene-2-yl)-2-propynoate (2n) were
furnished in yields from 78% to 81% (entries 11 – 13).
It was noteworthy that the hetero-aromatic groups were
also well-tolerated in the transformation under the op-
timal conditions, for methyl 3-(2-furanyl)-2-propynoate
(2o) and methyl 3-(2-thiophenyl)-2-propynoate (2p)
were obtained in 75% and 78% yields, respectively (en-
tries 14 and 15). Also, ethyl 3-phenyl-2-propynoate 2q
was produced under the optimal conditions in 88% yield
(entry 16).
in
the
system.
As
shown,
(3b),
propionitrile
propionitrile
(3c),
Table 2 Substrate scope for the synthesis of propynoates[a]
Entry
2
(Het)Ar, R
Yield (%)b
1
2
2b
2c
4-CH3C6H4, CH3
2-CH3C6H4, CH3
84
92

Page 3 of 8
ner, polyaryl decorated substrates such as
3-oxo-3-(4,4’-biphenyl) propionitrile (3j) and
3-oxo-3-(naphthalene-2-yl) propionitrile (3k) offered
biphenyl or 2-naphthyl fused 2-propynenitriles 4j and
4k in 89% and 83% yields, respectively (entries 10 and
11).
Table 3 Substrate scope for the synthesis of 2-propynenitriles[a]
Scheme 1. Proposed mechanism
Entry
4
Ar
Ph
Yield (%)b
Furthermore, to demonstrate the scalability of the
one-pot alkynylation method for preparing propynoates
and propynenitriles, gram-scale experiments were car-
ried out as shown in Scheme 2. Under the optimized
conditions and in the same concentration (0.1 M), 10
mmol of the substrates 1a or 3a furnished 1.25 g 2a and
0.96 g 4a, in 78% and 76% yields, respectively, reason-
ably lower than the yields of small-scale reactions (0.30
to 0.50 mmol). And the good results showed the prom-
ise of the synthetic method for larger-scale synthesis of
some rare alkynyl derivatives.
1
2
4a
4b
4c
4d
4e
4f
85
82
85
83
91
86
90
85
90
89
83
4-CH3C6H4
3-CH3C6H4
2-CH3C6H4
3,4-(CH3O)2C6H3
4-ClC6H4
3
4
5
6
7
4g
4h
4i
2-ClC6H4
8
4-BrC6H4
O
COOMe
COOMe
9
2-BrC6H4
10
11
4j
4-PhC6H4
1a, 1.78 g
2a, 1.25 g, 78% yield
One-pot Preparation
4k
2-Naphthyl
10 mmol scale
0.1 M in THF
O
[a] Conditions: i) 3 (0.50 mmol), LiHMDS (1.0 M in THF, 0.55
CN
mmol), dry THF (5.0 mL) at -60 oC for 30 min; ii)
CN
o
ClP(O)(OEt)2 (0.6 mmol) at -60 C and then at r.t. for 30 min;
iii) LiHMDS (1.0 M in THF, 0.75 mmol) at -60 oC 1 h. [b] Iso-
lated yields.
3a, 1.45 g
4a, 0.96 g, 76% yield
Scheme 2. Gram-scale experiments
Conclusions
Based on previously demonstrated mechanistic study by
our group,[13] a plausible mechanism for the present
one-pot preparation of propynoates and propynenitriles
was proposed. As illustrated in Scheme 1, treatment of
the substrates with a strong base LiHMDS (1.1 equiva-
lents) led to an intermediate A, which allowed an easy
in situ generation of another intermediate B in the eno-
late form. Then, a nucleophilic attack of the intermedi-
ate B to ClP(O)(OEt)2 formed enol phosphate interme-
diate C, which underwent an elimination step upon the
treatment of an additional 1.5 equivalents of LiHMDS,
affording the corresponding products propynoates or
propynenitriles. However, efforts to isolate of the key
intermediate C with flash column chromatography
(SiO2) failed, probably because that C=C bonds de-
composed during the workup procedure.
In summary, we have disclosed a practical synthetic
method towards propynoates and propynenitriles in a
one-pot manner. The products of great importance were
obtained in good to excellent yields with broad substrate
scope and high efficiency, which was illustrated well by
the scaled-up experiments.
Materials and method
Solvents, reagents were purchased as analytical grade
chemicals and used without further purification. Col-
umn chromatography was performed on silica gel
(200-300 mesh). H and 13C NMR spectra were record-
1
ed on a Varian INOVA-400 spectrometer in deuterated
chloroform at 25 °C with residual solvent peaks as in-
1
ternal standards (δ = 7.26 ppm for H-NMR and δ =
77.16 ppm for 13C-NMR). Chemical shifts (δ) are re-
ported in ppm, and spin-spin coupling constants (J) are
given in Hz, while multiplicities are abbreviated by s
(singlet), d (doublet), t (triplet), q (quartet) and m (mul-
tiplet). Mass spectra were recorded on a ThermoFinni-

Page 4 of 8
gan MAT95XP microspectrometer and high resolution
mass spectra (HRMS) were recorded on an Agilent
Technologies Accurate Mass Q-TOF 6530 microspec-
trometer. Melting points were recorded on a national
standard melting point apparatus (Model: Taike XT-4)
and were uncorrected.
Hz, 1H), 7.23 (d, J = 7.6 Hz, 1H), 7.17 (t, J = 7.5 Hz,
1H), 3.83 (s, 3H), 2.48 (s, 3H). 13C-NMR (100 MHz,
CDCl3) (ppm): 154.69, 142.3, 133.5, 130.8, 129.9,
125.9, 119.4, 85.6, 84.3, 52.8, 20.6. MS (EI) m/z (%):
91.1 (18), 115.1(100), 116.1 (52), 129.1 (12), 143.1 (74),
174.1 (M+, 47). HRMS (EI): calcd. for [C11H10O2]+:
174.0681, Found 174.0675.
Experimental
Methyl 3-(4-methoxyphenyl)-2-propynoate (2d)
Under the nitrogen atmosphere, LiHMDS (0.55 mL, 1.0
mol/L in THF/ethylbenzene) was added dropwise to the
solution of substrate 1 or 3 (0.50 mmol) in dry THF (5.0
mL) at referred temperature and the mixture was kept
stirred for additional 30 min. Then ClP(O)(OEt)2 (0.60
mmol) was added to the above solution. After addition,
the mixture was warmed up to the room temperature
gradually and kept stirred for another 30 min. The mix-
ture was then re-cooled to the referred temperature,
LiHMDS (0.75 mL, 1.0 mol/L in THF/ethylbenzene)
was added dropwise to the solution. The mixture was
kept stirred at the maintained temperature for another 1
h, then, quenched with saturated NH4Cl (aq.). The water
phase extracted with EtOAc (20 mL × 3). The combined
organic phase was dried over anhydrous Na2SO4; sol-
vent was removed by rotary evaporation and the result-
ing oily mixture was purified with silica gel flash col-
umn chromatograph (elute: hexanes), giving the desired
products 2 or 4 in noted yields.
Colorless crystal, m.p.: 34 - 36 oC. Yield: 91% (87 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.53 (d, J = 8.6 Hz,
2H), 6.88 (d, J = 8.7 Hz, 2H), 3.83 (s, 3H), 3.82(s, 3H).
13C-NMR (100 MHz, CDCl3) (ppm): 161.7, 154.9,
135.1, 114.4, 111.43, 87.5, 79.95, 55.5, 52.8. MS (EI)
m/z (%):116.1 (14), 132.1 (74), 144.1 (19), 159.1 (100),
190.1 (M+, 56). HRMS (EI): calcd. for [C11H10O3]+:
190.0630, Found 190.0624.
Methyl 3-(2,5-dimethoxyphenyl)-2-propynoate (2e)
Colorless crystal, m.p.: 69 - 71 oC. Yield: 92% (101 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.03 (d, J = 3.1 Hz,
1H), 6.95 (dd, J = 9.1, 3.1 Hz, 1H), 6.81 (d, J = 9.1 Hz,
1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.74 (s, 3H). 13C-NMR
(100 MHz, CDCl3) (ppm): 156.3, 154.6, 153.1, 119.0,
118.8, 112.3, 109.0, 84.1, 83.6, 56.43, 55.9, 52.8. MS
(EI) m/z (%):77.1 (23), 131.1 (36), 89.1 (30), 147.1 (39),
189.1 (17), 205.1(44),220.1 (M+, 100). HRMS (EI):
calcd. for [C12H12O4]+: 220.0736, Found 220.0731.
Data
Methyl 3-phenyl-2-propynoate (2a)
Methyl 3-(1,3-benzodioxol-5-yl)-2-propynoate (2f)
Colorless oil. Yield: 85% (68 mg). 1H-NMR (400 MHz,
CDCl3) (ppm): 7.58 (d, J = 7.9 Hz, 2H), 7.45 (t, J = 7.4
Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H), 3.84 (s, 3H).
13C-NMR (100 MHz,CDCl3) (ppm): 154.6, 133.1,
130.8, 128.7, 119.7, 86.7, 80.5, 52.9. MS (EI) m/z (%):
75.1 (14), 102.1 (26), 129.1 (100), 118.1 (100), 160.1
(M+, 29). HRMS (EI): calcd. for [C10H8O2]+: 160.0524,
Found 160.0519.
Colorless crystal, m.p.: 71 – 73 oC. Yield: 84% (86 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.15 (d, J = 8.1 Hz,
1H), 7.00 (s, 1H), 6.80 (d, J = 8.1 Hz, 1H), 6.01 (s, 2H),
3.82 (s, 3H). 13C-NMR (100 MHz, CDCl3) (ppm): 154.7,
150.2, 147.8, 129.0, 112.7, 112.6, 108.9, 101.9, 87.1,
79.5, 52.8; MS (EI) m/z (%):63.1 (28), 83.0(21),119.1
(34), 171.1 (48), 202.1(M+, 100); HRMS (EI): calcd. for
[C11H8O4]+: 204.0423, found 204.0427.
Methyl 3-(4-methylphenyl)-2-propynoate (2b)
Methyl 3-(4-fulorophenyl)-2-propynoate (2g)
Colorless crystal, m.p.: 63 - 65 oC. Yield: 84% (73 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.48 (d, J = 8.0 Hz,
2H), 7.18 (d, J = 8.0 Hz, 2H), 3.83 (s, 3H), 2.38 (s, 3H).
13C-NMR (100 MHz, CDCl3) (ppm): 154.8, 141.5,
133.2, 129.5, 116.5, 87.2, 80.2, 52.9, 21.9. MS (EI) m/z
(%): 115.1 (14),116.1 (38), 143.1 (100), 174.1 (M+, 47).
HRMS (EI): calcd. for [C11H10O2]+: 174.0681, Found
174.0675.
Colorless crystal, m.p.: 52 – 54 oC. Yield: 82% (73 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.51 (dd, J = 8.6,
5.4 Hz, 2H), 7.00 (dd, J = 8.6, 5.4 Hz, 2H), 3.77 (s, 3H).
13C-NMR (100 MHz, CDCl3) (ppm): 164.1 (JC-F = 252
Hz), 154.5, 135.4 (JC-F = 9.0 Hz), 116.3 (JC-F = 22.0 Hz),
85.6, 80.4, 52.96; MS (EI) m/z (%):74.1 (5), 99.1 (19),
120.1 (39), 147.1 (100), 178.1 (M+, 27). HRMS (EI):
calcd. for [C10H7O2F]+: 178.0430, found 178.0428.
Methyl 3-(2-methylphenyl)-2-propynoate (2c)
Methyl 3-(4-chlorophenyl)-2-propynoate (2h)
Colorless oil. Yield: 92% (80 mg). 1H-NMR (400 MHz,
CDCl3) (ppm): 7.53 (d, J = 7.6 Hz, 1H), 7.33 (t, J = 7.5
o
Off-white solid, m.p.: 87-89 C. Yield: 83% (81 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.51 (d, J = 8.4 Hz,

Page 5 of 8
2H), 7.36 (d, J = 8.4 Hz, 2H), 3.84 (s, 3H). 13C-NMR
(100 MHz, CDCl3) (ppm): 154.4, 137.3, 134.3, 129.2,
118.1, 85.3, 81.3, 53.0; MS (EI) m/z (%):74.1 (12), 99.1
(24), 136.0 (46), 163.0 (100), 194.0 (M+, 29). HRMS
(EI): calcd. for [C10H7O2Cl]+: 194.0135, found
194.0134.
134.4, 134.0, 132.7, 128.5, 128.4, 128.3, 128.1, 128.0,
127.1, 116.8, 87.1, 80.7, 53.0; MS (EI) m/z (%):150.1
(28), 152.1 (69), 179.1 (94), 210.1 (M+, 100). HRMS
(EI): calcd. for [C14H10O2]+: 210.0681, found 210.0674.
Methyl
3-(6-methoxynaphthalene-2-yl)-2-propynoate
(2n)
Methyl 3-(4-bromophenyl)-2-propynoate (2i)
Off-white solid, m.p.: 103-105 oC; Yield: 80% (96 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 8.06 (s, 1H), 7.70 (t,
J = 8.0 Hz, 2H), 7.53 (dd, J = 8.5, 1.0 Hz, 1H), 7.18 (dd,
J = 9.0, 2.4 Hz, 1H), 7.11 (d, J = 2.0 Hz, 1H), 3.92 (s,
3H), 3.85 (s, 3H). 13C-NMR (100 MHz, CDCl3) (ppm):
159.4, 154.8, 135.6, 134.3, 129.9, 129.1, 128.2, 127.3,
120.1, 114.2, 106.0, 87.7, 80.3, 55.5, 52.9; MS (EI) m/z
(%): 139.1 (27), 165.1 (28), 182.1 (72), 209.1 (61),
240.1 (M+, 100). HRMS (EI): calcd. for [C15H12O3]+:
240.0786, found 240.0780.
o
Off-white solid, m.p.: 97-99 C. Yield: 80% (95 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.52 (d, J = 8.3 Hz,
2H), 7.44 (d, J = 8.3 Hz, 2H), 3.84 (s, 3H). 13C-NMR
(100 MHz, CDCl3) (ppm): 154.4, 134.4, 132.2, 125.7,
118.6, 85.4, 81.4, 53.04; MS (EI) m/z (%): 100.1 (27),
128.1 (49), 180.0 (100), 182.0 (96), 207.0 (24), 238.0
(M+, 23). HRMS (EI): calcd. for [C10H7O2Br]+:
237.9629, found 237.9629.
Methyl 3-(4-iodophenyl)-2-propynoate (2j)
Methyl 3-(2-furanyl)-2-propynoate (2o)
Off-white solid, m.p.: 100-102 oC. Yield: 78% (112 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.52 (d, J = 8.4 Hz,
2H), 7.44 (d, J = 8.4 Hz, 2H), 3.84 (s, 3H). 13C-NMR
(100 MHz, CDCl3) (ppm): 154.4, 134.4, 132.2, 125.7,
118.6, 85.4, 81.4, 53.0; MS (EI) m/z (%): 74.1 (15),
99.1 (26), 121.1 (48), 203.0 (90), 227.0 (100), 286.0
(M+, 30); HRMS (EI): calcd. for [C10H7O2I]+: 285.9491,
found 285.9485.
Light yellow liquid. Yield: 75% (56 mg). 1H-NMR (400
MHz, CDCl3) (ppm): 7.51 (s, 1H), 6.94 (d, J = 3.4 Hz,
1H), 6.47 (dd, J = 3.3, 1.8 Hz, 1H), 3.84 (s, 3H).
13C-NMR (100 MHz, CDCl3) (ppm): 154.2, 146.4,
134.7, 121.3, 111.7, 85.7, 76.9, 53.0; MS (EI) m/z (%):
63.1 (20), 92.1 (76), 109.1 (4), 119.1 (100), 150.1 (M+,
40). HRMS (EI): calcd. for [C8H6O3]+: 150.0317, found
150.0313.
Methyl 3-(3,4-dichlorophenyl)-2-propynoate (2k)
Methyl 3-(2-thiophenyl)-2-propynoate (2p)
Light yellow solid, m.p.: 68-70 oC. Yield: 80% (91 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.66 (d, J = 1.4 Hz,
1H), 7.46 (d, J = 8.3 Hz, 1H), 7.40 (dd, J = 8.3, 1.4 Hz,
1H), 3.84 (s, 3H). 13C-NMR (100 MHz, CDCl3) (ppm):
154.1, 135.7, 134.6, 133.3, 132.0, 130.9, 119.6, 83.6,
81.9, 53.1; MS (EI) m/z (%): 74.1 (10), 98.2 (25), 133.1
(14), 170.1 (50), 197.0 (100), 229.1 (M+, 2). HRMS (EI):
calcd. for [C10H6O2Cl2]+: 227.9745, found 227.9749.
Light yellow liquid, Yield: 78% (65 mg). 1H-NMR (400
MHz, CDCl3) (ppm): 7.48 (dd, J = 8.9, 4.4 Hz, 2H),
7.05 (dd, J = 4.8, 4.0 Hz, 1H), 3.84 (s, 3H). 13C-NMR
(100 MHz, CDCl3) (ppm): 154.5, 136.7, 131.3, 127.7,
119.5, 84.7, 80.7, 52.9; MS (EI) m/z (%): 63.1 (14),
89.1 (45), 107.1 (41), 135.1 (100), 166.0 (M+, 53).
HRMS (EI): calcd. for [C8H6O2S]+: 166.0089, found
166.0086.
Methyl 3-(4,4’-biphenyl)-2-propynoate (2l)
Ethyl 3-phenyl-2-propynoate (2q)
o
Off-white solid,, m.p.: 70-72 C.. Yield: 78% (92 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.66 (d, J = 8.3 Hz,
2H), 7.60 (dd, J = 7.7, 5.8 Hz, 4H), 7.46 (t, J = 7.5 Hz,
2H), 7.39 (t, J = 7.2 Hz, 1H), 3.86 (s, 3H). 13C-NMR
(100 MHz, CDCl3) (ppm): 154.6, 143.6, 139.9, 133.6,
129.1, 128.3, 127.4, 127.2, 118.3, 86.7, 81.1, 52.9; MS
(EI) m/z (%): 176.1 (44), 178.1 (95), 205.1 (100), 236.1
( M+, 81). HRMS (EI): calcd. for [C16H12O2]+: 236.0837,
found 236.0836.
Colorless oil, Yield: 88% (77 mg). 1H-NMR (400 MHz,
CDCl3) (ppm): 7.58 (d, J = 7.3 Hz, 2H), 7.44 (t, J = 7.4
Hz, 1H), 7.37 (t, J = 7.5 Hz, 2H), 4.30 (q, J = 7.1 Hz,
2H), 1.35 (t, J = 7.1 Hz, 3H). 13C-NMR (100 MHz,
CDCl3) (ppm): 154.2, 133.1, 130.7, 128.7, 119.8, 86.2,
80.8, 62.2, 14.2; MS (EI) m/z (%): 75.1 (13), 102.1 (64),
129.1 (100), 130.1 (17), 174.1 (M+, 18). HRMS (EI):
calcd. for [C11H10O2]+: 174.0681, found 174.0676.
Methyl 3-(naphthalene-2-yl)-2-propynoate (2m)
3-Phenyl-2-propynenitriles (4a)
Off-white solid, m.p.: 123 – 124 oC. Yield: 81% (85 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 8.15 (s, 1H), 7.86 –
7.79 (m, 3H), 7.54 (ddd, J = 10.3, 9.6, 7.2 Hz, 3H), 3.87
(s, 3H). 13C-NMR (100 MHz, CDCl3) (ppm): 154.6,
Colorless oil, Yield: 85% (54 mg). 1H-NMR (400 MHz,
CDCl3) (ppm): 7.61 (d, J = 8.1 Hz, 2H), 7.54 (t, J = 7.5
Hz, 1H), 7.42 (t, J = 7.7 Hz, 2H). 13C-NMR (100 MHz,
CDCl3) (ppm): 133.7, 132.0, 129.0, 117.7, 105.6, 83.1,

Page 6 of 8
63.3; MS (EI) m/z (%): 77 (6), 89 (3), 140 (13), 164
(10), 224 (2), 281 (59), 293 (17), 309 (36), 324 (M+,
100); HRMS (EI): calcd. for [C9H5N]+: 127.0422, found
127.0420.
3-(2-Chlorophenyl)-2-Propynenitrile (4g)
o
Colorless crystal. m.p.: 92-94 C. Yield: 90% (72 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.63 (d, J = 7.7 Hz,
1H), 7.47 (d, J = 3.9 Hz, 2H), 7.35 – 7.29 (m, 1H).
13C-NMR (100 MHz, CDCl3) (ppm): 138.4, 135.4,
132.9, 130.1, 127.1, 118.3, 105.3, 79.4, 67.4; MS (EI)
m/z (%): 51.0 (12), 99.1 (24), 100.1 (17), 126.1 (46),
161.1 (M+, 100). HRMS (EI): calcd. for [C9H4NCl]+:
161.0032, found 161.0032.
3-(4-Methylphenyl)-2-Propynenitrile (4b)
Colorless oil, Yield: 82% (58 mg). 1H-NMR (400 MHz,
CDCl3) (ppm): 7.50 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0
Hz, 2H), 2.41 (s, 3H). 13C-NMR (100 MHz, CDCl3)
(ppm): 142.9, 133.6, 129.8, 114.6, 105.8, 83.6, 62.9,
22.0; MS (EI) m/z (%): 63.1 (10), 113.1 (16), 114.1 (40),
140.1 (100), 141.1 (M+, 87). HRMS (EI): calcd. for
[C10H7N]+: 141.0578, found 141.0573.
3-(4-Bromophenyl)-2-Propynenitrile (4h)
Off-white solid. m.p.: 108-110 oC . Yield: 85% (88 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.57 (d, J = 8.3 Hz,
2H), 7.47 (d, J = 8.4 Hz, 2H). 13C-NMR (100 MHz,
CDCl3) (ppm): 134.8, 132.5, 127.1, 116.6, 105.4, 81.9,
64.3; MS (EI) m/z (%): 51.0 (5), 75.1 (7), 99.0 (20),
100.0 (15), 126.1 (17), 205.0 (M+, 100); HRMS (EI):
calcd. for [C9H4NBr]+: 204.9527, found 204.9528.
3-(3-Methylphenyl)-2-Propynenitrile (4c)
Colorless oil, Yield: 85% (60 mg). 1H-NMR (400 MHz,
CDCl3) (ppm): 7.40 (d, J = 6.6 Hz, 2H), 7.35 – 7.24 (m,
2H), 2.35 (s, 3H). 13C-NMR (100 MHz, CDCl3) (ppm):
139.0, 134.0, 132.9, 130.8, 128.9, 117.5, 105.7, 83.5,
62.9, 21.3; MS (EI) m/z (%): 113.1 (14), 114.1 (35),
140.1 (100), 141.1 (M+, 90). HRMS (EI): calcd. for
[C10H7N]+: 141.0578, found 141.0572.
3-(2-Bromophenyl)-2-Propynenitrile (4i)
o
Off-white solid. m.p.: 58-60 C . Yield: 90% (108 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.68 – 7.58 (m,
2H), 7.43 – 7.33 (m, 2H); 13C-NMR (100 MHz, CDCl3)
(ppm): 135.6, 133.2, 132.9, 127.6, 127.2, 120.6, 105.4,
80.9, 66.8; MS (EI) m/z (%): 51.0 (3), 99.1 (17), 126.1
(41), 203.1 (7), 205.0(M+, 100). HRMS (EI): calcd. for
[C9H4NBr]+: 204.9527 found 204.9527.
3-(2-Methylphenyl)-2-Propynenitrile (4d)
Colorless oil. Yield: 83% (59 mg). 1H-NMR (400 MHz,
CDCl3) (ppm): 7.58 (d, J = 7.7 Hz, 1H), 7.43 (t, J = 7.6
Hz, 1H), 7.29 (d, J = 7.9 Hz, 1H), 7.24 (t, J = 7.6 Hz,
1H), 2.50 (s, 3H). 13C-NMR (100 MHz, CDCl3) (ppm):
143.5, 134.2, 131.9, 130.2, 126.2, 117.5, 105.7, 82.5,
66.5, 20.6; MS (EI) m/z (%): 57.2 (6), 63.1 (24), 114.1
(38), 139.1 (9), 140.1 (100), 141.1 (M+, 83). HRMS (EI):
calcd. for [C10H7N]+: 141.0578, found 140.0598.
3-(4,4’-Biphenyl)-2-Propynenitrile (4j)
o
Off-white solid. m.p.: 83-85 C . Yield: 89% (90 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.71 – 7.57 (m,
6H), 7.49 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.2 Hz, 1H).
13C-NMR (100 MHz, CDCl3) (ppm): 144.8, 139.5,
134.1, 129.2, 128.7, 127.6, 127.3, 116.22, 105.7, 83.2,
63.8; MS (EI) m/z (%): 61.1 (8), 86.1 (35), 115.1 (9),
146.1 (74), 173.1 (100), 203.1 (M+, 2). HRMS (EI):
calcd. for [C15H9N]+: 203.0735, found 203.0738.
3-(3,4-Dimethoxyphenyl)-2-Propynenitrile (4e)
o
Yellow foamy solid, m.p.: 98-100 C. Yield: 91% (85
1
mg). H-NMR (400 MHz, CDCl3) (ppm): 7.25 (dd, J =
8.4, 1.6 Hz, 1H), 7.03 (d, J = 1.3 Hz, 1H), 6.84 (d, J =
8.4 Hz, 1H), 3.91 (s, 3H), 3.87 (s, 3H). 13C-NMR (100
MHz, CDCl3) (ppm): 152.6, 149.0, 128.2, 115.2, 111.3,
109.2, 105.9, 83.9, 62.3, 56.1; MS (EI) m/z (%): 75.1
(11), 89.1 (17), 116.1 (20), 126.1 (9), 144.1 (20), 172.1
(28), 187.1 (M+, 100). HRMS (EI): calcd. for
[C11H9O2N]: 187.0633, found 187.0634.
3-(Naphthalene-2-yl)-2-Propynenitrile (4k)
o
Yellowish solid. m.p.: 72 – 74 C . Yield: 83% (73 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 8.18 (s, 1H), 7.86
(dd, J = 7.5, 5.6 Hz, 3H), 7.58 (ddd, J = 16.5, 11.4, 3.5
Hz, 3H). 13C-NMR (100 MHz, CDCl3) (ppm): 135.6,
134.4, 132.50, 128.9, 128.9, 128.3, 128.1, 127.9, 127.6,
114.7, 105.7, 83.7, 63.3; MS (EI) m/z (%): 75.1 (7),
99.1(3), 150.1 (19), 175.1 (6), 177.1 (M+, 100). HRMS
(EI): calcd. for [C13H7N]+: 177.0578, found 177.0576.
3-(4-Chlorophenyl)-2-Propynenitrile (4f)
o
Off-white solid，m.p.: 94-96 C. Yield: 86% (69 mg).
1H-NMR (400 MHz, CDCl3) (ppm): 7.55 (d, J = 8.5 Hz,
2H), 7.40 (d, J = 8.5 Hz, 2H). 13C-NMR (100 MHz,
CDCl3) (ppm): 138.4, 133.0, 127.1, 118.3, 105.3, 79.4,
67.4; MS (EI) m/z (%): 51.0 (12), 75.1 (6), 99.1 (27),
126.1 (78), 161.1 (M+, 100). HRMS (EI): calcd. for
[C9H4NCl]+: 161.0032, found 161.0033.
Acknowledgement
The authors are grateful for the financial support from
the National Natural Science Foundation of China

Page 7 of 8
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Page 8 of 8
Entry for the Table of Contents
Page No.
One-pot Synthesis of Propynoates
and Propynenitriles
Fan Shu, Qingjuan Zheng, Wanrong
Dong,* Zhihong Peng* and Delie An*
An efficient transformation towards ester or nitril substituted al-
kynes was herein described. The practical methodology was con-
ducted at low temperature (-78 or -60 oC) in a one-pot manner
with assistance of LiHMDS. The base-induced protocol exhibits
good functional groups tolerance (up to 28 examples) and high ef-
ficiency (up to 92% yields) towards substituted acetylenes of great
synthetic significance, which was also well-demonstrated by the
gram-scale reactions.