Synthesis of terminal allenes through copper-mediated cross-coupling of ethyne with N-tosylhydrazones or α-diazoesters

Article abstract of DOI:10.1021/jo502316q

Ethyne is employed as coupling partner in coppermediated cross-coupling reactions with N-tosylhydrazones and α-diazoacetate, leading to the development of a new synthetic method for terminal allenes. With this novel coupling method, the terminal allenes w

Full text of DOI:10.1021/jo502316q

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Note
Synthesis of Terminal Allenes through Copper-mediated Cross-
Coupling of Ethyne with N-Tosylhydrazones or alpha-Diazoesters
Fei Ye, Chengpeng Wang, Xiaoshen Ma, Mohammad
Lokman Hossain, Ying Xia, Yan Zhang, and Jianbo Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo502316q • Publication Date (Web): 03 Dec 2014
Downloaded from http://pubs.acs.org on December 8, 2014
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Synthesis of Terminal Allenes through Copper-mediated Cross-
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Coupling of Ethyne with N-Tosylhydrazones or α-Diazoesters
Fei Ye,† Chengpeng Wang,† Xiaoshen Ma,† Mohammad Lokman Hossain,† Ying Xia,† Yan Zhang† and
Jianbo Wang*,†,‡
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†Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic
Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking
University, Beijing 100871, China; ‡State Key Laboratory of Organometallic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, China
wangjb@pku.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
ABSTRACT: Ethyne is employed as coupling partner in copper-mediated cross-coupling reactions with
N-tosylhydrazones and α-diazoacetate, leading to the development of a new synthetic method for
terminal allenes. With this novel coupling method, the terminal allenes were obtained in good yields and
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with excellent functional group tolerance. Copper carbene migratory insertion is proposed as the key
step in these transformations.
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Allenes have found increasing applications in organic synthesis.1 Consequently, various synthetic
methods to access allenes have been developed over the past decades.2 In general, SN2'-type
displacement of propargyl alcohol derivatives with organocopper species is the most widely practiced
method.3 On the contrary, there are only few reports in the literature on the allene synthesis based on
coupling reactions.4 Crabbé and co-workers in 1979 reported the terminal allene synthesis through
CuBr-mediated reaction of 1-alkynes and formaldehyde in the presence of diisopropylamine.5 Recently,
this reaction has been significantly improved and expanded by Ma and coworkers.6,7 In 1980, a reaction
of ethyl diazoacetate with acetylene to generate terminal allene mediated by CuO was reported by
Shapiro and co-workers.8
Scheme 1. Allene Synthesis through Cu Carbene Migratory Insertion
We have recently reported an alternative allene synthesis by Cu(I)-catalyzed cross-coupling
reaction of N-tosylhydrazones with terminal alkynes.9 The reaction is proposed to follow Cu(I) carbene
migratory insertion process.10 However, our previous method by using terminal alkynes as coupling
partner is only applicable to the synthesis of di- and tri-substituted allenes (Scheme 1, a and b). On the
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other hand, the copper-catalyzed coupling reactions between terminal alkynes and diazoacetates were
studied by Jones and Vidal.11 More recently this type of coupling reactions have been developed into the
methods for the synthesis of allenoates and 3-alkynoates by Fox and Fu, respectively.12,13 Herein we
report the copper-mediated synthesis of terminal allenes by the application of ethyne as the cross-
coupling partner under atmospheric pressure conditions. The cross-coupling reaction of N-
tosylhydrazones with a balloon of ethyne is highly efficient and operationally simple, leading to the
straightforward synthesis of mono- and 1,1-disubstituted allenes. The reaction can also be applied to α-
diazoacetates.12,14
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At the outset of this study, N-tosylhydrazone 1a and acetylene 2 were subjected to the coupling
reaction under the similar reaction conditions as we previously reported for the synthesis of 1,3-
disubstituted allene (20 mol% CuI, 2.0 equiv of LiOtBu and 2.0 mL dioxane).9b The desired allene
product 3a could be isolated in 5% yield (Table 1, entry 1). Further study of the solvent effect indicated
that the reaction in DMF afforded improved yield (enter 4), while the reaction in toluene or MeCN gave
poor results (entries 2 and 3). Screening the reaction concentration and the loading of catalyst led to the
conclusion that more concentrated solution and higher loading of CuI were favorable for the reaction
(entries 5-9). Thus, in the presence of 1.0 equiv of CuI, 2.0 equiv of LiOtBu and 1.0 mL DMF, the
allene 3a could be isolated with an optimized yield of 76% (entry 9). Finally, other bases such as KOtBu
and KOMe were examined, but the corresponding reactions only gave trace amount of the allene
product (entries 10 and 11).
Table 1. Optimization of Reaction Conditionsa
Ph
Ph
Ph
Ph
CuI
NNHTs
1a
+
H
H
2
3a
entry cat. (equiv)
base (equiv) solvent (mL) yield (%)b
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1
2
CuI (0.2)
CuI (0.2)
CuI (0.2)
CuI (0.2)
CuI (0.2)
CuI (0.4)
CuI (0.6)
CuI (0.6)
CuI (1)
LiOtBu (2)
LiOtBu (2)
LiOtBu (2)
LiOtBu (2)
LiOtBu (2)
LiOtBu (2)
LiOtBu (2)
LiOtBu (2)
LiOtBu (2)
KOtBu (2)
KOMe (2)
dioxane (2)
MeCN (2)
toluene (2)
DMF (2)
5
trace
trace
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3
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4
5
DMF (1.5)
DMF (1.5)
DMF (1.5)
DMF (1)
14
6
32
7
46
8
52
9
DMF (1)
76
10
11
CuI (1)
DMF (1)
trace
trace
CuI (1)
DMF (1)
aThe reaction was carried out with 1a (0.4 mmol) at 90 oC under an atmosphere of acetylene (balloon)
for 0.5 h. bIsolated yields. DMF: N,N-dimethylformamide.
With the optimized reaction conditions, we proceeded to explore the substrate scope, firstly by
using a series of N-tosylhydrazones 1a-p derived from aryl ketones (Scheme 2). In all the cases, the
corresponding 1,1-disubstituted allene products 3a-p could be isolated in moderate yields. The reaction
is not significantly affected by the electronic effects of the substituents on the aromatic ring of the N-
tosylhydrazones which were derived from diaryl ketones. Both electron-withdrawing groups (such as
fluoro, chloro, and phenyl group), and electron-donating group (such as methyl and alkoxyl group),
show little influence on the reaction (3a-g, 3i-k). Besides, the reactions with the N-tosylhydrazones
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derived from aryl methyl ketones also afforded the desired products (3l and 3m). Notably, the reaction
proceeded well with the N-tosylhydrazones bearing naphthyl, thiophenyl and furanyl groups (3h, 3n and
3p). However, the N-tosylhydrazones derived from other aliphatic ketones, such as cyclohexanone, 1,2-
diphenylethanone and 4-phenylbutan-2-one, are not suitable substrates for this reaction because 1,2-
hydrogen shift becomes competitive and the side products are difficult to separate from the allenes. It
was noted that there were two major side reactions in these transformations: the dimerization of the
carbene intermediates that generated olefins, and the reaction of Ts anion with carbene or diazo
intermediates that gave sulfonyl compounds.
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Scheme 2. The Substrate Scope of N-Tosylhydrazones Derived from Aromatic Ketonesa
CuI (1.0 equiv)
LiOtBu (2.0 equiv)
DMF, 90 oC, 0.5 h
Ar
Ar
+ H
H
NNHTs
1a p
R
R
-
3a p
-
2
X
X
X
b
3a,
X = H, 76%
, X = Me, 64%
, X = F, 68%
3e
, X = Cl, 62%
3b
3c
3d
3f
, X = Ph, 58%
3h
, 63%
3g
, X = OMe, 81%
, X = OMe, 85%
Me
Me
3j
X
X
X'
'
Me
, X = Me, X = OMe, 74%
3l
3i
, X = p-I, 70%
, 75%
'
3m
, X = m-NO2, 44%
3k
, X = Cl, X = OCF3, 63%
S
S
S
S
O
3n
3o
3p
, 53%
, 74%
, 65%
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aThe reaction conditions are as following: N-tosylhydrazones 1a-p (0.4 mmol), acetylene 2 (1 atm), CuI
(1.0 equiv), LiOtBu (0.8 mmol), DMF (1.0 mL), 90 oC, 0.5 h. bIsolated yield.
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Next, we explored the reaction scope with N-tosylhydrazones derived from aromatic aldehydes,
which would afford mono-substituted allenes as the products. As shown in Scheme 3, a series of N-
tosylhydrazones derived from benzaldehydes bearing para, ortho and meta substituents all reacted
smoothly with acetylene 2 under the optimized reaction conditions (Scheme 3, 5a-h). Moreover, the N-
tosylhydrazones derived from benzaldehydes bearing multiple substituents also worked well (5i-k).
Finally, the reaction with N-tosylhydrazone derived from naphthaldehyde gave the corresponding allene
product 5l in 81% yield.
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Scheme 3. The Substrate Scope of N-Tosylhydrazones Derived from Aromatic Aldehydesa
aThe reaction conditions are as following: N-tosylhydrazones 4a-l (0.4 mmol), acetylene 2 (1 atm), CuI
(1.0 equiv), LiOtBu (0.8 mmol), DMF (1.0 mL), 90 oC, 0.5 h. bIsolated yield.
To validate whether this strategy can be practically useful, scale-up experiments were carried out
for N-tosylhydrazones 1a and 4f. The reactions afforded the corresponding allene products 3a and 5f in
gram-scale, albeit in diminished yields as compared with the small scale experiments (eq 1 and 2).
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CuI (1.0 equiv)
LiOtBu (2.0 equiv)
Ph
Ph
Ph
H
H
NNHTs +
DMF, 90 oC, 0.5 h
(1)
(2)
Ph
8
9
2
3a
1a (30 mmol)
, 47% (2.7 g)
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20
CuI (1.0 equiv)
LiOtBu (2.0 equiv)
NNHTs
+ H
H
MeO
MeO
DMF, 90 oC, 0.5 h
5f
, 44% (1.9 g)
4f
2
(30 mmol)
During the substrate scope study shown in Scheme 3, we noticed that in some cases 1-methyl-2-
aryl acetylene derivatives could be isolated as side products, in particular for the reactions with aromatic
N-tosylhydrazones bearing electron-donating substituents. We reasoned that the formation of 1-methyl-
2-aryl acetylene side products were attributed to the base-promoted rearrangement of the primary allene
products. Thus, by extending the reaction time and increasing the amount of base, the 1-methyl-2-aryl
acetylene derivatives might turn to be the major products. This was proved to be the case. As
summarized in Scheme 4, carrying out the coupling reaction for 4 h with increased base (LiOtBu, 3
equiv) could afford the 1-methyl-2-aryl acetylene products in moderate yields.
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Scheme 4. Formation of 1-Methyl-2-aryl Acetylene Derivatives a
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aAll the reaction conditions are as following: N-tosylhydrazones 4b-c, 4e-f, 4i, 4m-n (0.4 mmol),
acetylene 2 (1 atm), CuI (1.0 equiv), LiOtBu (1.2 mmol), DMF (1.0 mL), 90 oC, 4.0 h. bIsolated yield.
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Encouraged by the successful coupling of acetylene gas with N-tosylhydrazones, we then
proceeded to extend this transformation to α-diazo esters.10 To our delight, under modified reaction
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conditions [CuI (1.0 equiv), 1,10-phenanthrene (1.0 equiv), DMF, 60 C, 2 h], the expected allene
products could be isolated in moderate yields (Scheme 5). Notably, the side products due to 1,2-
hydrogen shift, which is a common reaction for metal carbene species, were not observed in most
cases.15
Scheme 5. Cross-coupling with α-Diazo Acetatesa
CuI (1.0 equiv)
1,10-Phen (1.0 equiv)
N2
+
H
H
R
CO2R'
DMF, 60 oC, 2 h
R
CO2R'
8a-g
7a-g
2
Ph
( )n
( )8
CO2Et
nC8H17
CO2Et
CO2Et
8a, n = 1, 76%
8b, n = 3, 93%
8c, 73%
8d, 60%
X
EtO2C
CO2Bn
CO2Me
8g, 43%
8e, X = nPr, 89%
8f, X = cyclopropyl, 90%
a The reaction conditions are as following: α-diazo ester 7a-h (0.4 mmol), acetylene 2 (1 atm), CuI (1.0
equiv), 1,10-phenanthrene (1.0 equiv), DMF (1.5 mL), 60 oC, 2.0 h. bIsolated yield.
In conclusion, we have developed a novel strategy for the synthesis of mono- and 1,1-
disubstituted terminal allenes. This transformation has the following features: 1) the reaction is
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operationally simple by using a balloon of acetylene gas; 2) cheap copper catalyst is used; 3) the N-
tosylhydrazones are easily prepared from the corresponding ketones or aldehydes and they are stable
and easy to purify; 4) the reaction is efficient and tolerates various functional groups. With those
advantages, we expect that this method will find wide applications for the synthesis of terminal allenes.
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EXPERIMENTAL SECTION
General Experimental Methods. Except the gram-scale experiments, all reactions were
performed under acetylene gas atmosphere in a 10 mL microwave tube (Note: the reactions are not
carried out under microwave conditions). DMF and acetylene gas obtained from commercial suppliers
were used without further purifications. For the gram-scale experiments, the reaction was carried out in
round-bottle flask. For chromatographic purification, 200-300 mesh silica gel (Qingdao, China) was
employed. Chemical shifts for H NMR (400 MHz) and 13C NMR (100 MHz) spectra are reported
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relative to the chemical shift of tetramethylsilane (TMS). IR spectra are reported in wave numbers, cm−1.
For HRMS measurements, the mass analyzer is FT-ICR.
N-Tosylhydrazones 1a-p and 4a-l were prepared according to the literature procedure.9 α-Diazo
esters 7a-h were prepared by a two-step procedure as reported in the literature.16 Unless otherwise noted,
materials obtained from commercial suppliers were used without further purifications.
General procedure for the preparation of N-tosylhydrazones 1a-p, 4a-l. A solution of TsNHNH2
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(5 mmol) in methanol (5 mL) was stirred and heated to 60 C until the TsNHNH2 was completely
dissolved. Then the ketone or aldehydes was dropped to the mixture slowly. After approximately 5-30
min the crude products was obtained as precipitates. The precipitates were washed by petroleum ether,
then they were dried in vacuo to afford the corresponding N-tosylhydrazone which was used for the
coupling without further purification.
General procedure for Cu(I)-mediated coupling of 1a-p and 4a-l with acetylene. CuI (76.2 mg,
100 mol%), LiOtBu (0.80 mmol, 64.0 mg) and N-tosylhydrazone (0.40 mmol) were suspended in DMF
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(1.0 mL) in a 10 mL microwave tube under an atmosphere of acetylene gas (a balloon equipped with a
needle was inserted through a rubber plug to the reaction system). The reaction solution was stirred at
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90 C for 20 min. After cooling to room temperature, the resulting mixture was filtered through a short
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path of silica gel, eluting with ethyl acetate and diethyl ether. The filtrate was washed by brine twice to
remove DMF. Then the aqueous phase was extracted by ethyl acetate and diethyl ether. The organic
phases were combined and the volatile compounds were removed in vacuo with rotvap. The crude
residue was purified by column chromatography (SiO2, hexane) to afford the pure allene product.
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Propa-1,2-diene-1,1-diyldibenzene (3a).17 yield 76% (58 mg). H NMR (400 MHz, CDCl3) δ 7.36-
7.30 (m, 8H), 7.26-7.24 (m, 2H), 5.24 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 209.9, 136.2, 128.4,
128.3, 127.2, 109.1, 78.0.
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4,4'-(Propa-1,2-diene-1,1-diyl)bis(methylbenzene) (3b).18 yield 64% (56 mg). H NMR (400 MHz,
CDCl3) δ 7.25 (d, J = 8.0 Hz, 4H), 7.14 (d, J = 8.0 Hz, 4H), 5.22 (s, 2H), 2.35 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 209.6, 136.9, 133.4, 129.1, 128.3, 108.8, 77.7, 21.1.
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4,4'-(Propa-1,2-diene-1,1-diyl)bis(fluorobenzene) (3c).19 yield 68% (62 mg). H NMR (400 MHz,
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CDCl3) δ 7.30-7.27 (m, 4H), 7.05-7.00 (m, 4H), 5.25 (s, 2H); C NMR (100 MHz, CDCl3) δ 209.5,
162.1 (d, J = 247.0 Hz), 132.1 (d, J = 3.2 Hz), 129.9 (d, J = 8.0 Hz), 115.4 (d, J = 21.7 Hz), 107.5, 78.4.
1
4,4'-(Propa-1,2-diene-1,1-diyl)bis(methoxybenzene) (3d).18 yield 85% (86 mg). H NMR (400 MHz,
CDCl3) δ 7.27 (d, J = 8.8 Hz, 4H), 6.87 (d, J = 8.8 Hz, 4H), 5.20 (s, 2H), 3.80 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 209.4, 158.8, 129.4, 128.7, 113.8, 108.2, 77.7, 55.2.
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1-Chloro-4-(1-phenylpropa-1,2-dien-1-yl)benzene (3e).20 yield 62% (56 mg). H NMR (400 MHz,
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CDCl3) δ 7.34-7.31 (m, 4H), 7.29-7.26 (m, 5H), 5.27 (s, 2H); C NMR (100 MHz, CDCl3) δ 209.8,
135.8, 134.8, 133.0, 129.6, 128.6, 128.5, 128.3, 127.4, 108.3, 78.4.
1
4-(1-Phenylpropa-1,2-dien-1-yl)-1,1'-biphenyl (3f). yield 58% (62 mg). H NMR (400 MHz, CDCl3)
δ 7.61-7.56 (m, 4H), 7.45-7.33 (m, 9H), 7.31-7.27 (m, 1H), 5.29 (s, 2H); 13C NMR (100 MHz, CDCl3)
δ 210.0, 140.7, 140.0, 136.2, 135.2, 128.8, 128.7, 128.5, 128.4, 127.3, 127.1, 127.0, 108.9, 78.2; IR
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(film) 1932, 1486, 842, 766, 732, 696 cm-1; EI-MS (m/z, relative intensity) 268 (M+, 100), 253 (21), 244
(24), 207 (73), 191 (26), 165 (22); HRMS (ESI) calcd for C21H17 [(M+H)+] 269.1325, found: 269.1322.
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1-Methoxy-4-(1-phenylpropa-1,2-dien-1-yl)benzene (3g).18 yield 81% (72 mg). H NMR (400 MHz,
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CDCl3) δ 7.37-7.31 (m, 4H), 7.29-7.26 (m, 3H), 6.88 (d, J = 8.8 Hz, 2H), 5.23 (s, 2H), 3.81 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 209.7, 158.9, 136.5, 129.5, 128.4, 128.3, 127.1, 113.9, 108.7, 77.9,
55.3.
1-(1-Phenylpropa-1,2-dien-1-yl)naphthalene (3h).21 yield 63% (61 mg). 1H NMR (400 MHz, CDCl3)
δ 7.90-7.85 (m, 3H), 7.51-7.50 (m, 2H), 7.47-7.44 (m, 1H), 7.40-7.36 (m, 1H), 7.25-7.24 (m, 4H),
7.20-7.18 (m, 1H), 5.24 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 209.1, 136.7, 133.9, 133.8, 132.0,
128.7, 128.4, 128.3, 128.2, 127.8, 126.8, 126.1, 126.0, 125.8, 125.6, 106.4, 77.7.
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1,2-Dimethyl-4-(1-phenylpropa-1,2-dien-1-yl)benzene (3i). yield 75% (66 mg). H NMR (400 MHz,
CDCl3) δ 7.37-7.30 (m, 4H), 7.27-7.23 (m, 1H), 7.14 (s, 1H), 7.12-7.07 (m, 2H), 5.22 (s, 2H), 2.26 (s,
3H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 209.7, 136.6, 136.5, 135.7, 133.6, 129.7, 129.6,
128.4, 128.3, 127.1, 125.9, 109.0, 77.8, 19.8, 19.4; IR (film) 2920, 1934, 1492, 1449, 854, 764, 697 cm-
1; EI-MS (m/z, relative intensity) 220 (M+, 90), 205 (100), 189 (21), 178 (12), 165 (11), 115 (6), 89 (6);
HRMS (ESI) calcd for C17H17 [(M+H)+] 221.1325, found: 221.1326.
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1-Methoxy-3-(1-(m-tolyl)propa-1,2-dien-1-yl)benzene (3j). yield 74% (70 mg). H NMR (400 MHz,
CDCl3) δ 7.27-7.14 (m, 4H), 7.08 (d, J = 7.6 Hz, 1H), 6.95-6.92 (m, 2H), 6.82 (dd, J = 2.2, 8.2 Hz,
1H), 5.24 (s, 2H), 3.78 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 209.7, 159.6, 138.0, 137.8,
136.0, 129.3, 129.1, 128.2, 128.0, 125.5, 120.9, 114.0, 112.7, 109.1, 78.0, 55.2, 21.4; IR (film) 2961,
1931, 1597, 1486, 1260, 1089, 856, 794 cm-1; EI-MS (m/z, relative intensity) 236 (M+, 100), 221 (53),
205 (22), 193 (19), 178 (39), 165 (14), 152 (9); HRMS (ESI) calcd. for C17H17O [(M+H)+] 237.1274,
found: 237.1277.
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1-Chloro-3-(1-(3-(trifluoromethoxy)phenyl)propa-1,2-dien-1-yl)benzene (3k). yield 63% (78 mg). H
NMR (400 MHz, CDCl3) δ 7.39-7.34 (m, 2H), 7.29-7.24 (m, 3H), 7.22-7.20 (m, 2H), 7.16-7.14 (m,
1H), 5.35 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 209.9, 149.4, 137.9, 137.5, 134.5, 129.8, 129.7,
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128.4, 127.6, 126.6, 126.4, 120.9, 120.5 (q, J = 257.5 Hz), 119.8, 107.5, 79.3; IR (film) 1934, 1255,
1217, 1164, 789, 694 cm-1; EI-MS (m/z, relative intensity) 310 (M+, 97), 286 (16), 275 (100), 251 (23),
225 (28), 189 (34), 178 (25); HRMS (ESI) calcd for C16H11ClF3O [(M+H)+] 311.0445, found: 311.0451.
1-(Buta-2,3-dien-2-yl)-4-iodobenzene (3l). yield 70% (72 mg). 1H NMR (400 MHz, CDCl3) δ 7.63 (d,
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J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 5.02 (q, J = 3.0 Hz, 2H), 2.05 (t, J = 3.0 Hz, 3H); C NMR
(100 MHz, CDCl3) δ 208.9, 137.6, 137.3, 136.4, 127.6, 99.2, 91.7, 16.5; IR (film) 2923, 1942, 1483,
1071, 1004, 854, 820, 799 cm-1; EI-MS (m/z, relative intensity) 256 (M+, 100), 241 (8), 128 (97), 114
(10), 102 (12), 77 (13); HRMS (ESI) calcd for C10H10I [(M+H)+] 256.9822, found: 256.9823.
1-(Buta-2,3-dien-2-yl)-3-nitrobenzene (3m). yield 44% (31 mg). 1H NMR (400 MHz, CDCl3) δ 8.22
(s, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.2 Hz, 1H), 7.48 (dt, J = 1.2, 8.0 Hz, 1H), 5.15 (br, 2H),
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2.14 (br, 3H); C NMR (100 MHz, CDCl3) δ 209.2, 148.6, 139.0, 131.5, 129.0, 121.3, 120.3, 98.7,
78.2, 16.5; IR (film) 2962, 1943, 1528, 1345, 1260, 1089, 799 cm-1; EI-MS (m/z, relative intensity) 175
(M+, 62), 128 (100), 102 (16), 77 (10), 63 (10), 51 (14); HRMS (ESI) calcd for C10H10NO2 [(M+H)+]
176.0706, found: 176.0701.
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3-(1-Phenylpropa-1,2-dien-1-yl)thiophene (3n). yield 74% (59 mg). H NMR (400 MHz, CDCl3) δ
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7.43-7.41 (m, 2H), 7.37-7.33 (m, 2H), 7.32-7.28 (m, 2H), 7.14-7.11 (m, 2H), 5.24 (s, 2H); C NMR
(100 MHz, CDCl3) δ 210.0, 136.8, 136.2, 128.4, 128.1, 127.9, 127.4, 125.5, 122.3, 104.8, 78.0; IR
(film) 1932, 1260, 1078, 1028, 850, 787, 698 cm-1; EI-MS (m/z, relative intensity) 198 (M+, 100), 173
(17), 165 (36), 152 (13), 113 (6); HRMS (ESI) calcd for C13H11S [(M+H)+] 199.0576, found: 199.0575.
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3,3'-(Propa-1,2-diene-1,1-diyl)dithiophene (3o). H NMR (400 MHz, CDCl3) yield 65% (53 mg).δ
7.33-7.31 (m, 2H), 7.25-7.23 (m, 2H), 7.17-7.16 (m, 2H), 5.24 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
210.1, 136.7, 127.8, 125.5, 122.1, 100.4, 78.1; IR (film) 2961, 2924, 1260, 1080, 1018, 790, 665 cm-1;
EI-MS (m/z, relative intensity) 204 (M+, 100), 188 (15), 180 (40), 171 (45), 165 (59), 115 (18); HRMS
(ESI) calcd for C11H9S2 [(M+H)+] 205.0140, found: 205.0141.
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3-(1-(Thiophen-3-yl)propa-1,2-dien-1-yl)furan (3p). yield 53% (40 mg). H NMR (400 MHz, CDCl3)
δ 7.50 (s, 1H), 7.43 (t, J = 1.6 Hz, 1H), 7.31 (m, 1H), 7.25 (s, 1H), 7.17 (dd, J = 1.0, 5.0 Hz, 1H), 6.49
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(d, J = 1.0 Hz, 1H), 5.23 (s, 2H); C NMR (100 MHz, CDCl3) δ 209.6, 143.1, 140.1, 136.3, 127.5,
125.6, 121.6, 121.3, 110.3, 96.8, 78.2; IR (film) 2960, 2924, 1260, 1085, 1023, 873, 792, 670 cm-1; EI-
MS (m/z, relative intensity) 188 (M+, 11), 165 (100), 152 (5), 115 (12); HRMS (ESI) calcd for C11H9OS
[(M+H)+] 189.0369, found: 189.0365.
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Methyl 4-(propa-1,2-dien-1-yl)benzoate (5a).22 yield 40% (28 mg). H NMR (400 MHz, CDCl3) δ
7.97 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 6.20 (t, J = 6.8 Hz, 1H), 5.21 (d, J = 6.8 Hz, 2H), 3.90
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 210.6, 166.9, 139.0, 131.4, 129.9, 126.5, 93.6, 79.2, 52.0.
4-(Propa-1,2-dien-1-yl)-1,1'-biphenyl (5b).23 yield 55% (42 mg). H NMR (400 MHz, CDCl3) δ
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7.59-7.53 (m, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.37-7.30 (m, 3H), 6.20 (t, J = 6.8 Hz, 1H), 5.17 (d, J = 6.8
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 210.0, 140.8, 139.7, 133.0, 128.7, 127.3, 127.2, 127.1, 126.9,
93.6, 78.9.
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N,N-Dimethyl-4-(propa-1,2-dien-1-yl)aniline (5c). yield 47% (30 mg). H NMR (400 MHz, CDCl3)
δ 7.17 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 8.8 Hz, 2H), 6.11 (t, J = 6.8 Hz, 1H), 5.10 (d, J = 6.8 Hz, 2H),
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2.94 (s, 6H); C NMR (100 MHz, CDCl3) δ 209.2, 149.7, 127.5, 121.5, 112.8, 93.6, 78.5, 40.6; IR
(film) 2927, 1611, 1520, 908, 859, 817, 731 cm-1; EI-MS (m/z, relative intensity) 159 (M+, 60), 129 (85),
103 (61), 77 (100); HRMS (ESI) calcd for C11H14N [(M+H)+] 160.1121, found: 160.1123.
N-(4-(Propa-1,2-dien-1-yl)phenyl)acetamide (5d).24 yield 67% (46 mg). H NMR (400 MHz,
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CD3COCD3) δ 9.20 (s, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 6.23 (t, J = 6.8 Hz, 1H),
5.16 (d, J = 6.8 Hz, 2H), 2.07 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ 210.4, 168.8, 139.5, 129.4,
127.8, 120.2, 94.0, 79.0, 24.3.
1-Methoxy-2-(propa-1,2-dien-1-yl)benzene (5e).7 yield 62% (36 mg). 1H NMR (400 MHz, CDCl3) δ
7.39 (dd, J = 1.2, 7.6 Hz, 1H), 7.17 (dt, J = 1.2, 8.4 Hz, 1H), 6.92 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 8.4
Hz, 1H), 6.57 (t, J = 6.8 Hz, 1H), 5.10 (d, J = 6.8 Hz, 2H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 210.2, 155.8, 127.9, 127.7, 122.3, 120.8, 110.9, 87.8, 78.0, 55.5.
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1-Methoxy-4-(propa-1,2-dien-1-yl)benzene (5f).24 yield 73% (43 mg). 1H NMR (400 MHz, CDCl3) δ
7.22 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.4 Hz, 2H), 6.12 (t, J = 6.8 Hz, 1H), 5.11 (d, J = 6.8 Hz, 2H), 3.79
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 209.3, 158.7, 127.7, 126.1, 114.1, 93.3, 78.7, 55.3.
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1-Bromo-3-(propa-1,2-dien-1-yl)benzene (5g).25 yield 56% (44 mg). H NMR (400 MHz, CDCl3) δ
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7.45 (s, 1H), 7.32 (d, J = 7.6 Hz, 1H), 7.21-7.14 (m, 2H), 6.09 (t, J = 6.8 Hz, 1H), 5.19 (d, J = 6.8 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 209.9, 136.3, 130.0, 129.8, 129.5, 125.3, 122.8, 93.0, 79.4.
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1-Bromo-4-(propa-1,2-dien-1-yl)benzene (5h).22 yield 64% (50 mg). H NMR (400 MHz, CDCl3) δ
7.42 (d, J = 8.2 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 6.10 (t, J = 6.8 Hz, 1H), 5.14 (d, J = 6.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 209.8, 133.0, 131.7, 128.2, 120.5, 93.2, 79.3.
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5-(Propa-1,2-dien-1-yl)benzo[d][1,3]dioxole (5i).26 yield 63% (40 mg). H NMR (400 MHz, CDCl3)
δ 6.84-6.83 (m, 1H), 6.76-6.71 (m, 2H), 6.09 (t, J = 6.8 Hz, 1H), 5.94 (s, 2H), 5.13 (d, J = 6.8 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 209.3, 148.0, 146.7, 127.9, 120.3, 108.3, 106.6, 101.0, 93.8, 79.1.
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1,2-Dichloro-4-(propa-1,2-dien-1-yl)benzene (5j). yield 54% (40 mg). H NMR (400 MHz, CDCl3)
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δ 7.36-7.34 (m, 2H), 7.11-7.09 (m, 1H), 6.07 (t, J = 6.8 Hz, 1H), 5.19 (d, J = 6.8 Hz, 2H); C NMR
(100 MHz, CDCl3) δ 210.0, 134.3, 132.7, 130.4, 128.2, 125.9, 92.4, 79.7; IR (film) 1941, 1473, 1133,
1031, 884, 854, 802 cm-1; EI-MS (m/z, relative intensity) 184 (41), 149 (100), 113 (17), 87 (6), 63 (8);
HRMS (EI) calcd for C9H6Cl2 [M+] 183.9847, found: 183.9855.
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4-Bromo-3-(propa-1,2-dien-1-yl)phenol (5k). yield 71% (60 mg). H NMR (400 MHz, CDCl3) δ
7.36 (d, J = 8.8 Hz, 1H), 6.95 (d, J = 3.2 Hz, 1H), 6.59-6.54 (m, 2H), 5.17 (d, J = 6.8 Hz, 2H), 5.08 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 210.5, 154.8, 134.6, 133.7, 116.1, 114.6, 113.2, 93.0, 79.1; IR
(film) 3298, 1942, 1571, 1430, 1289, 1023, 870, 804 cm-1; EI-MS (m/z, relative intensity) 207 (90), 149
(57), 131 (100), 102 (46), 77 (53), 63 (15), 51 (27); HRMS (ESI) calcd for C9H6BrO [(M-H)-] 208.9608,
found: 208.9605.
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2-(Propa-1,2-dien-1-yl)naphthalene (5l).27 yield 81% (54 mg). H NMR (400 MHz, CDCl3) δ 7.79-
7.75 (m, 3H), 7.64 (s, 1H), 7.51-7.48 (m, 1H), 7.46-7.39 (m, 2H), 6.33 (t, J = 6.8 Hz, 1H), 5.21 (d, J =
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6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 210.3, 133.6, 132.6, 131.4, 128.2, 127.7, 127.6, 126.2,
125.6, 125.4, 124.6, 94.3, 79.1.
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General procedure for the formation of 1-methyl-2-aryl acetylene derivatives 6a-g. CuI (76.2 mg,
100 mol%), LiOtBu (1.20 mmol, 96.0 mg) and N-tosylhydrazone (0.40 mmol) were suspended in DMF
(1.0 mL) in a 10 mL microwave tube under an atmosphere of acetylene gas (a balloon equipped with a
needle was inserted through a rubber plug to the reaction system). The resulting solution was stirred at
90 oC for 4 h. After cooling down to room temperature, the reaction mixture was filtered through a short
path of silica gel, eluting with ethyl acetate and diethyl ether. The filtrate was washed by brine twice to
remove DMF. Then the aqueous phase was extracted by ethyl acetate and diethyl ether. The organic
phases were combined and the volatile compounds were removed in vacuo with rotvap. The crude
residue was purified by column chromatography (SiO2, hexane) to afford the pure 1-methyl-2-aryl
acetylene derivative products.
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1-Methoxy-4-(prop-1-yn-1-yl)benzene (6a).28 yield 50% (29 mg). H NMR (400 MHz, CDCl3) δ
7.32 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.78 (s, 3H), 2.02 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 159.0, 132.8, 116.1, 113.8, 84.0, 79.4, 55.2, 4.2.
4-(Prop-1-yn-1-yl)-1,1'-biphenyl (6b).29 yield 32% (25 mg). 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J
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= 7.6 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H), 7.46-7.42 (m, 4H), 7.34 (t, J = 6.8 Hz, 1H), 2.08 (s, 3H); C
NMR (100 MHz, CDCl3) δ 140.5, 140.2, 131.9, 128.8, 127.4, 127.0, 126.9, 123.0, 86.5, 79.6, 4.4.
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N,N-dimethyl-4-(prop-1-yn-1-yl)aniline (6c).28 yield 54% (34 mg). H NMR (400 MHz, CDCl3) δ
7.26 (d, J = 8.8 Hz, 2H), 6.60 (d, J = 8.8 Hz, 2H), 2.93 (s, 6H), 2.02 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 149.6, 132.4, 112.7, 111.9, 82.9, 80.2, 40.2, 4.3.
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1-Methoxy-2-(prop-1-yn-1-yl)benzene (6d).30 yield 43% (25 mg). H NMR (400 MHz, CDCl3) δ
7.38-7.36 (m, 1H), 7.26-7.22 (m, 1H), 6.90-6.84 (m, 2H), 3.87 (s, 3H), 2.11 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 159.7, 133.6, 128.9, 120.4, 113.0, 110.4, 90.0, 75.7, 55.7, 4.7.
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5-(Prop-1-yn-1-yl)benzo[d][1,3]dioxole (6e).31 yield 49% (31 mg). H NMR (400 MHz, CDCl3) δ
6.90 (dd, J = 1.4, 8.0 Hz, 1H), 6.84 (d, J = 1.4 Hz, 1H), 6.71 (d, J = 8.0 Hz, 1H), 5.93 (s, 2H), 2.01 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 147.3, 147.2, 125.7, 117.3, 111.5, 108.3, 101.1, 83.9, 79.4, 4.2.
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1,3-Dimethyl-2-(prop-1-yn-1-yl)benzene (6f). yield 74% (43 mg). H NMR (400 MHz, CDCl3) δ
7.05-6.99 (m, 3H), 2.41 (s, 6H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 140.0, 126.8, 126.5,
123.7, 94.0, 77.3, 21.1, 4.5; IR (film) 2918, 1648, 1592, 1467, 1377, 769, 734 cm-1; EI-MS (m/z, relative
intensity) 144 (M+, 94), 128 (100), 115 (20), 102 (6), 77 (8), 63 (10); HRMS (ESI) calcd for C11H12NO
[(M+NO)+] 174.0913, found: 174.0912.
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1,3-Dichloro-2-(prop-1-yn-1-yl)benzene (6g). yield 62% (46 mg). H NMR (400 MHz, CDCl3) δ
7.29 (d, J = 8.0 Hz, 2H), 7.10 (t, J = 8.0 Hz, 1H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.1,
128.2, 127.4, 123.7, 97.5, 74.0, 4.8; IR (film) 2919, 2256, 1556, 1429, 1195, 790, 774, 723 cm-1; EI-MS
(m/z, relative intensity) 184 (M+, 48), 149 (100), 113 (24), 87 (10), 74 (11), 63 (9); HRMS (EI) calcd for
C9H6Cl2 (M+) 183.9847, found: 183.9855.
General procedure for Cu(I)-mediated coupling of α-diazo acetate 7a-g. CuI (76.2 mg, 100
mol%), 1,10-phenanthroline (72 mg, 100 mol%) and diazo compound 7a-g (0.4 mmol) were suspended
in DMF (1.5 mL) in a 10 mL microwave tube under a atmosphere of acetylene gas (a balloon equipped
with a needle was inserted through a rubber plug to the reaction system). The resulting solution was
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stirred at 60 C for 2 hours. After cooling down to room temperature, the reaction mixture was filtered
through a short path of silica gel, eluting with ethyl acetate and diethyl ether. The filtrate was washed by
brine twice to remove DMF. Then the aqueous phase was extracted by ethyl acetate and diethyl ether.
The organic phases were combined and the volatile compounds were removed in vacuo with rotvap. The
crude residue was purified by column chromatography (SiO2, hexane:ethyl acetate = 30:1). The
combined products were further purified via productive thin-layer chromatography (SiO2, hexane:ethyl
acetate = 30:1).
Ethyl 2-benzylbuta-2,3-dienoate (8a).32 yield 76% (61 mg). 1H NMR (400 MHz, CDCl3) δ 7.30-7.20
(m, 5H), 5.09 (t, J = 2.6 Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H), 3.57 (t, J = 2.4 Hz, 2H), 1.25 (t, J = 7.2 Hz,
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3H); C NMR (100 MHz, CDCl3) δ 214.4, 166.8, 139.1, 128.8, 128.2, 126.3, 100.3, 79.2, 61.1, 34.9,
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Ethyl 5-phenyl-2-vinylidenepentanoate (8b). yield 93% (86 mg). H NMR (400 MHz, CDCl3) δ
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7.28-7.24 (m, 2H), 7.18-7.14 (m, 3H), 5.12 (t, J = 3.2 Hz, 2H), 4.19 (q, J = 7.2 Hz, 2H), 2.65 (t, J = 7.6
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Hz, 2H), 2.30-2.25 (m, 2H), 1.83-1.75 (m, 2H), 1.26 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl3)
δ 213.7, 167.1, 142.1, 128.3, 128.2, 125.7, 100.1, 79.0, 60.8, 35.2, 29.6, 27.5, 14.2; IR (film) 2935,
1940, 1710, 1603, 1496, 1454, 1367, 1258, 1214, 1152, 1097, 1029, 849, 797, 746, 699 cm-1; EI-MS
(m/z, relative intensity) 229 (4), 215 (14), 201 (7), 157 (100), 141 (19), 129 (32), 115 (8), 104 (44), 91
(53), 77 (13), 65 (12), 51 (8); HRMS (ESI) calcd for C15H19O2 [(M+H)+]: 231.1380, found: 231.1383.
Ethyl 2-vinylidenedecanoate (8c). yield 73% (65 mg). 1H NMR (400 MHz, CDCl3) δ 5.11 (t, J = 3.0
Hz, 2H), 4.20 (q, J = 7.2 Hz, 2H), 2.24-2.19 (m, 2H), 1.46-1.41 (m, 2H), 1.30-1.26 (m, 13H), 0.88 (t, J
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= 6.8 Hz, 3H); C NMR (100 MHz, CDCl3) δ 213.7, 167.3, 100.4, 78.7, 60.9, 31.8, 29.3, 29.2, 29.1,
28.0, 27.9, 22.6, 14.2, 14.1; IR (film) 2926, 2856, 1942, 1714, 1465, 1367, 1212, 1173, 1129, 1081,
1040, 844, 784 cm-1; EI-MS (m/z, relative intensity) 224 (M+, 13), 206 (13), 167 (13), 153 (22), 140 (21),
127 (100), 112 (30), 99 (84), 91 (24), 81 (84), 67 (61), 55 (73); HRMS (ESI) calcd for C14H25O2
[(M+H)+]: 225.1849, found: 225.1853.
1
Ethyl 2-vinylidenedodec-11-enoate (8d). yield 60% (60 mg). H NMR (400 MHz, CDCl3) δ 5.85-
5.75 (m, 1H), 5.10 (t, J = 3.0 Hz, 2H), 5.10-4.91 (m, 2H), 4.20 (t, J = 7.1 Hz, 2H), 2.24-2.19 (m, 2H),
2.06-2.01 (m, 2H), 1.45-1.26 (m, 15H); 13C NMR (100 MHz, CDCl3) δ 213.7, 167.2, 139.1, 114.1,
100.4, 78.7, 60.8, 33.7, 29.6, 26.3, 29.3, 29.0, 28.9, 27.9, 27.8, 14.2; IR (film) 2927, 2855, 1841, 1714,
1641, 1464, 1367, 1258, 1213, 1173, 1096, 1020, 910, 844, 806 cm-1; EI-MS (m/z, relative intensity)
250 (M+, 2), 235 (2), 221 (2), 205 (4), 189 (4), 177 (10), 169 (9), 161 (10), 154 (4), 135 (19), 127 (90),
114 (25), 107 (32), 99 (64), 81 (100), 67 (85), 51 (87); HRMS (ESI) calcd for C16H27O2 [(M+H)+]:
251.2006, found: 251.2008.
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Benzyl 2-vinylidenehexanoate (8e).33 yield 89% (82 mg). H NMR (400 MHz, CDCl3) δ 7.37-7.24
(m, 5H), 5.18 (s, 2H), 5.12 (t, J = 3.0 Hz, 2H), 2.27-2.22 (m, 2H), 1.49-1.39 (m, 2H), 1.37-1.32 (m, 2H),
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0.90 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 214.0, 167.1, 136.2, 128.4, 127.9, 127.7, 100.2,
78.9, 66.3, 30.0, 27.7, 22.1, 13.8.
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Benzyl 2-(cyclopropylmethyl)buta-2,3-dienoate (8f). yield 90% (82 mg). 1H NMR (400 MHz, CDCl3)
δ 7.37-7.24 (m, 5H), 5.19 (s, 2H), 5.15 (t, J = 3.0 Hz, 2H), 2.18-2.15 (m, 2H), 0.92-0.83 (m, 1H), 0.47-
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0.43 (m, 2H), 0.14-0.10 (m, 2H); C NMR (100 MHz, CDCl3) δ 214.4, 167.1, 136.1, 128.4, 127.9,
127.7, 100.1, 78.9, 66.4, 33.2, 9.6, 4.5; IR (film) 2960, 1966, 1710, 1498, 1456, 1376, 1258, 1212, 1135,
1069, 1018, 799, 687 cm-1; EI-MS (m/z, relative intensity) 183 (4), 169 (15), 155 (5), 104 (10), 91 (100),
77 (8), 65 (12); HRMS (ESI) calcd for C15H17O2 [(M+H)+]: 229.1223, found: 229.1226.
4-Ethyl 1-methyl 2-vinylidenesuccinate (8g). yield 43% (32 mg). 1H NMR (400 MHz, CDCl3) δ 5.24
(t, J = 2.2 Hz, 2H), 4.17 (q, J = 7.2 Hz, 2H)，3.77 (s, 3H), 3.27 (t, J = 2.2 Hz, 2H), 1.26 (t, J = 7.2 Hz,
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3H); C NMR (100 MHz, CDCl3) δ 214.6, 170.3, 166.7, 94.3, 79.5, 60.9, 52.4, 34.7, 14.1; IR (film)
2959, 2926, 2852, 1971, 1739, 1720, 1439, 1369, 1260, 1179, 1099, 1028, 863, 797 cm-1; EI-MS (m/z,
relative intensity) 156 (100), 141 (60), 124 (21), 111 (27), 97 (29), 83 (27), 79 (8), 69 (6), 59 (32), 51
(47); HRMS (ESI) calcd for C9H13O4[(M+H)+]: 185.0808, found: 185.0807.
ASSOCIATED CONTENTS
Supporting Information
Copies of 1H and 13C spectra for all products. This material is available free of charge via the Internet at
http://pubs.acs.org.
ACKNOWLEDGMENTS
The project is supported by National Basic Research Program (973 Program, No. 2012CB821600) and
Natural Science Foundation of China (Grant 21272010 and 21332002).
REFERENCES
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