CuI-catalyzed cross-coupling of N-tosylhydrazones with terminal alkynes: Synthesis of 1,3-disubstituted allenes

Article abstract of DOI:10.1021/jo3024686

A CuI-catalyzed synthesis of 1,3-disubstituted allenes from 1-alkynes by the reaction with various N-tosylhydrazones has been developed. This method, which uses readily available starting materials and is operationally simple, offers 1,3-disubstituted all

Full text of DOI:10.1021/jo3024686

Note
pubs.acs.org/joc
CuI-Catalyzed Cross-Coupling of N‑Tosylhydrazones with Terminal
Alkynes: Synthesis of 1,3-Disubstituted Allenes
Mohammad Lokman Hossain,†,§ Fei Ye,†,§ Yan Zhang,† and Jianbo Wang*,†,‡
†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
S
* Supporting Information
ABSTRACT: A CuI-catalyzed synthesis of 1,3-disubstituted
allenes from 1-alkynes by the reaction with various N-
tosylhydrazones has been developed. This method, which uses
readily available starting materials and is operationally simple,
offers 1,3-disubstituted allenes in moderate to good yields. The
reaction also tolerates various functional groups.
Scheme 1. Allene Synthesis through Cu-Carbene Migratory
Insertion
wing to the unique structural feature related to the
Opresence of two perpendicular π bonds, allenes are
particularly prone to undergo various transformations. Because
of their rich reactivity, allenes have been recognized as versatile
substrates or intermediates in modern organic synthesis.1,2
Allene moieties are also structural units of many natural
products and pharmacologically interesting compounds.3 It is
thus not surprising that numerous synthetic methodologies to
access such compounds have been explored in the past
decades.4 Among the various methods, the most general one
is based on an SN2′-type displacement of propargyl alcohol
derivatives with organocopper species.4,5
However, an allene synthesis based on a coupling reaction is
relatively less developed, and up to now, there are only a few
catalytic methods reported in the literature. Barrett and co-
workers demonstrated a cross-metathesis by employing the
Grubbs catalysts and observed that the terminal carbon of
allenes could be exchanged to afford symmetrically substituted
allenes, but with a considerable amount of polymeric side
products.6 Bertrand and co-workers employed a cationic Au(I)
complex for the catalytic coupling of enamines and terminal
allenes using N-tosylhydrazones derived from ketones.
However, the previously reported reaction is not suitable for
the synthesis of disubstituted allenes because the reaction did
not proceed well when N-tosylhydrazones derived from
aldehydes were employed as the substrates.
In this note, we report a modification of the previous reaction
conditions for the reaction of N-tosylhydrazones derived from
aldehydes. The reaction is now significantly simplified by only
using CuI as the catalyst, while in the previous reaction, a
complex bisoxazoline ligand is needed. The new reaction
conditions can be successfully applied to the cross-coupling of
N-tosylhydrazones derived from various aldehydes and terminal
alkynes, affording 1,3-disubstituted allenes in moderate to good
yields.
The study began with an evaluation of the reaction between
N-tosylhydrazone 1a with phenylacetylene 2a by surveying
different potential Cu(I) catalysts without using any ligand
(Table 1). With LiOtBu as the base and dioxane as the solvent,
(CuOTf)2·C6H6 proved to be ineffective, giving 3a only in trace
amounts (Table 1, entry 1). Both CuCl and CuBr showed
catalytic activity, affording the desired allene product 3a in 10
and 40% yield, respectively (Table 1, entries 2 and 3). To our
alkynes to afford allenes in good yields.7 In 1979, Crabbe
́
and
co-workers reported the CuBr-mediated reaction to form
terminal allenes from 1-alkynes and formaldehyde in the
presence of diisopropylamine.8 This reaction only works with
formaldehyde, thus it can only be applied to the synthesis of
monosubstituted allenes. Recently, Ma and co-workers
significantly improved this reaction.9 The same group also
expanded the reaction to aldehydes, morpholine, and terminal
alkynes by using ZnI2, which led to an efficient synthesis of 1,3-
disubstituted allenes.9b
Our group has recently developed a different approach
toward allenes by Cu(I)/bisoxazoline-catalyzed cross-coupling
reaction of N-tosylhydrazones with terminal alkynes.10,11
Mechanistically, it has been proposed that the reaction involves
a Cu-carbene migratory insertion process (Scheme 1).12 This
reaction provides a straightforward access to trisubstituted
Received: November 10, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo3024686 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
a
Table 1. Optimization of Reaction Conditions
Scheme 2. Substrate Scope of N-Tosylhydrazones
b
entry
catalyst (20 mol %)
base
solvent
yield (%)
1
2
(CuOTf)2·C6H6
LiOtBu
LiOtBu
LiOtBu
LiOtBu
NaOH
Cs2CO3
KOH
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
DCE
trace
10
CuCl
CuBr
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
3
40
4
78
5
50
6
15
7
8
8
K2CO3
Na2CO3
LiOtBu
LiOtBu
trace
trace
72
9
10
11
MeCN
33
a
Reaction conditions: 1a (0.88 mmol), 2a (0.4 mmol), base (3.5
b
equiv), solvent (5 mL). Isolated yields.
delight, with CuI as the catalyst, the yield of 3a could be
improved to 78% (Table 1, entry 4). Next, we examined the
effect of base on the reaction and observed that other
commonly used bases all gave inferior results (Table 1, entries
5−9). It was noted that Cs2CO3, which was the base used in
our previous study,10 afforded 3a in only 15% yield under the
current reaction conditions (Table 1, entry 6). Finally, two
other polar solvents, 1,2-dichloroethane (DCE) and MeCN,
were examined. The reaction with DCE afforded comparable
results, while in MeCN, the yield was diminished (Table 1,
entries 10 and 11). On the basis of the above experiments, the
optimized reaction conditions can be summarized as follows:
substrate ratio of 1a to 2a is 2.2:1, CuI (20 mol %), LiOtBu
(3.5 equiv), 1,4-dioxane (5 mL), 90 °C, 1 h (Table 1, entry 4).
With the optimized reaction conditions in hand, we next
explored the scope of this reaction with various N-
tosylhydrazones and terminal alkynes. First, we examined the
scope of N-tosylhydrazones by the reaction with 2a (Scheme
2). The reactions of N-tosylhydrazones derived from a variety
of aldehydes proceeded smoothly, affording the corresponding
products 3a−r in moderate to good yields.
a
Reaction conditions: N-tosylhydrazone (2.2 equiv), 2a (0.4 mmol),
CuI (20 mol %), LiOtBu (3.5 equiv), dioxane (5 mL), 90 °C, 1 h.
Isolated yield by column chromatography. CuI (40 mol %) was used.
b
c
a
Scheme 3. Substrate Scope of Terminal Alkynes
For the N-tosylhydrazones derived from aromatic aldehydes,
it is noted that the reactions were not significantly affected by
the substituents on the aromatic ring, although a slightly lower
yield was observed with m-nitrobenzaldehyde tosylhydrazone
(Scheme 2, 3g). Functional groups, such as allyloxy, methoxy,
acetoxy, and −OCH2CO2Et, are all tolerated in this reaction.
Moreover, the reaction with aliphatic tosylhydrazones also
proceeded well (Scheme 2, 3n, 3p, 3q, and 3r).
Next, the reaction scope was investigated for a variety of
terminal alkynes under the optimized reaction conditions
(Scheme 3). The reactions examined under the identical
reaction conditions afforded the corresponding allene products
in moderate to good yields.
To validate whether this allene synthesis can be practiced in
organic synthesis, scale-up experiments were carried out for
several substrates. To our delight, the reactions all proceeded
well and the corresponding allenes could be isolated on a gram-
scale (Scheme 4). Notably, the diazo intermediate is generated
in situ at a slow rate from the corresponding N-tosylhydrazone,
so the evolution of N2 gas is gentle even in scale-up
experiments.
a
Reaction condition: N-tosylhydrazone (2.2 equiv), alkyne (0.4
mmol), CuI (20 mol %), LiOtBu (3.5 equiv), dioxane (5 mL), 90
°C, 1 h. Isolated yield by column chromatography.
b
Finally, we have carried out experiments in a one-pot
reaction mode directly starting from the aldehydes. To our
delight, the one-pot procedure afforded similar results as
B
dx.doi.org/10.1021/jo3024686 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
atmosphere, ethynylbenzene 2a (40.8 mg, 0.4 mmol) was added to a
mixture of CuI (15.3 mg, 0.08 mmol), LitOBu (112 mg, 1.4 mmol),
and the N-tosylhydrazone 1a (241 mg, 0.88 mmol) in 1,4-dioxane (5
mL). The solution was stirred at 90 °C for 1 h, and the progress of the
reaction was monitored by TLC. Upon completion of the reaction, the
mixture was cooled to room temperature and was filtered through a
short silica gel column eluting with EtOAc. The solvent was removed
in vacuum to leave a crude mixture, which was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 1,3-diphenylpropa-1,2-diene 3a13 as a colorless oil (60 mg, 78%):
1H NMR (400 MHz, CDCl3) δ 6.50 (s, 2H), 7.11−7.14 (m, 2H),
7.20−7.27 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 98.4, 127.0,
127.3, 128.7, 133.6, 207.8.
Scheme 4. Gram-Scale Experiments
a
Reaction conditions: N-tosylhydrazone (2.2 equiv), alkyne (10
mmol), CuI (20 mol %), LiOtBu (3.5 equiv), dioxane (125 mL for
3a; 100 mL for 3n and 4e), 90 °C (for 3a) or 110 °C (for 3n and 4e),
1-Methyl-3-(3-phenylpropa-1,2-dienyl)benzene (3b). Following
the typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
b
2 h. Isolated yield by column chromatography.
1
pure 3b as a light yellow oil (55 mg, 67%): H NMR (400 MHz,
compared to the stepwise transformations (Scheme 5). This
CDCl3) δ 2.23 (s, 3H), 6.45−6.50 (m, 2H), 6.94−6.98 (m, 1H),
7.05−7.14 (m, 4H), 7.20−7.28 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 21.3, 98.3, 98.4, 124.2, 127.0, 127.2, 127.6, 128.2, 128.6,
128.7, 133.4, 133.7, 138.4, 207.7; IR (film, cm−1) 3027, 1937, 1603,
1410, 1261, 798, 695, 667; EI-MS (m/z, relative intensity) 206 (M+,
100), 191 (90), 178 (15), 165 (20), 89 (10); HRMS (EI) calcd for
C16H15 [(M + H)+] 207.1168, found 207.1166.
appreciably simplifies the allene preparation.
a
Scheme 5. One-Pot Preparation of Allenes
Buta-1,2-diene-1,4-diyldibenzene (3c).14 Following the typical
procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 3c as a colorless oil (48 mg, 58%): 1H NMR (400 MHz, CDCl3)
δ 3.40 (dd, J = 2.4, 7.2 Hz, 2H), 5.65 (dd, J = 7.2, 13.9 Hz, 1H), 6.09−
6.12 (m, 1H), 7.10−7.16 (m, 2H), 7.19−7.26 (m, 8H); 13C NMR
(100 MHz, CDCl3) δ 35.6, 94.4, 94.9, 126.3, 126.7, 126.8, 128.5,
128.6, 134.6, 140.0, 205.7.
4-(3-Phenylpropa-1,2-dienyl)benzonitrile (3d).15 Following the
typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether/EtOAc =
1
30:1) to afford pure 3d as a light yellow oil (56 mg, 65%): H NMR
(400 MHz, CDCl3) δ 6.52 (d, J = 6.4 Hz, 1H), 6.60 (d, J = 6.4 Hz,
1H), 7.17−7.19 (m, 1H), 7.25 (d, J = 4.4 Hz, 4H), 7.34 (d, J = 8.4 Hz,
2H), 7.50 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 97.6,
99.3, 110.5, 118.9, 127.1, 127.4, 127.8, 128.9, 132.4, 132.5, 138.8,
209.2.
a
Reaction conditions: Aldehyde (2.2 equiv), TsNHNH2 (2.2 equiv),
1-alkyne (0.4 mmol), CuI (20 mol %), LiOtBu (5.4 equiv), dioxane (5
mL), 90 °C, 1 h. Isolated yield by column chromatography.
b
1-(Allyloxy)-2-(3-phenylpropa-1,2-dienyl)benzene (3e). Following
the typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether/EtOAc =
1
In conclusion, we have developed a straightforward synthesis
of 1,3-disubstituted allenes from terminal alkynes and N-
tosylhydrazones by a CuI-catalyzed migratory insertion
reaction. The prominent features of this method include the
following: (1) N-tosylhydrazones are easily available from the
corresponding aldehydes; (2) the CuI catalyst is inexpensive,
and no ligand is required; (3) the reaction is simple to operate
and tolerates various functional groups. It is thus expected that
this method will be useful in organic synthesis.
60:1) to afford pure 3e as a light yellow oil (62 mg, 63%): H NMR
(400 MHz, CDCl3) δ 4.48 (d, J = 5.2 Hz, 2H), 5.18 (dd, J = 1.2, 10.8
Hz, 1H), 5.34 (dd, J = 1.6, 17.2 Hz, 1H), 5.92−6.02 (m, 1H), 6.47 (d,
J = 6.8 Hz, 1H), 6.77−6.82 (m, 2H), 6.96 (d, J = 6.8 Hz, 1H), 7.06−
7.13 (m, 2H), 7.19−7.33 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
69.3, 92.5, 97.8, 112.5, 117.4, 121.0, 122.3, 126.9, 127.0, 128.0, 128.3,
128.6, 133.3, 134.0, 155.2, 208.3; IR (film, cm−1) 2923, 1935, 1596,
1492, 1451, 1243, 1020, 792, 749, 690; EI-MS (m/z, relative intensity)
248 (M+, 15), 207 (100), 178 (60), 152 (12), 115 (10); HRMS (EI)
calcd for C18H17O [(M + H)+] 249.1274, found 249.1270.
4-(3-Phenylpropa-1,2-dienyl)biphenyl (3f).5d Following the typical
procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 3f as a white powder (59 mg, 55%): 1H NMR (400 MHz,
EXPERIMENTAL SECTION
■
General Experimental Methods. Except for the gram-scale
experiments, all reactions were performed under a nitrogen
atmosphere in a 20 mL Schlenk tube. For the gram-scale experiments,
the reactions were carried out in round-bottomed flasks. Dioxane was
dried over Na before use. For chromatographic purifications, 200−300
CDCl3) δ 6.52 (s, 2H), 7.19−7.34 (m, 10H), 7.44−7.49 (m, 4H); 13
C
NMR (100 MHz, CDCl3) δ 98.1, 98.5, 126.9, 127.0, 127.2, 127.3,
127.40, 127.44, 128.8, 132.6, 133.5, 140.2, 140.7, 208.1.
mesh silica gel was employed. H NMR (400 MHz) and 13C NMR
1
1-Nitro-3-(3-phenylpropa-1,2-dienyl)benzene (3g). Following the
typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether/EtOAc =
60:1) to afford pure 3g as a reddish oil (38 mg, 40%): 1H NMR (400
MHz, CDCl3) δ 6.57 (d, J = 6.4 Hz, 1H), 6.62 (d, J = 6.4 Hz, 1H),
7.17−7.20 (m, 1H), 7.24−7.27 (m, 4H), 7.39 (t, J = 8.0 Hz, 1H), 7.58
(d, J = 7.6 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 8.09 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 97.0, 99.5, 121.5, 122.0, 127.2, 127.8, 128.9,
129.5, 132.5, 132.6, 135.9, 148.7, 208.4; IR (film, cm−1) 2962, 1938,
(100 MHz) spectra were recorded in parts per million using
tetramethylsilane (TMS) as the internal standard. IR spectra are
reported in wavenumbers (cm−1). For HRMS measurements, the mass
analyzer is FT-ICR. N-Tosylhydrazones were prepared according to a
literature procedure.10 Unless noted otherwise, materials obtained
from commercial suppliers were used without further purifications.
Typical Procedure for the CuI-Catalyzed Cross-Coupling of
N-Tosylhydrazones and Terminal Alkynes. Under a nitrogen
C
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The Journal of Organic Chemistry
Note
1527, 1350, 1260, 1018, 799, 729, 693, 672; EI-MS (m/z, relative
intensity) 237 (M+, 50), 220 (15), 207 (72), 189 (100), 178 (15), 165
(35), 115 (25); HRMS (EI) calcd for C15H12NO2 [(M + H)+]
238.0863, found 238.0858.
δ 1.05 (s, 9H), 5.49 (d, J = 6.4 Hz, 1H), 6.10 (d, J = 6.4 Hz, 1H),
7.08−7.11 (m, 1H), 7.21 (d, J = 4.4 Hz, 4H); 13C NMR (100 MHz,
CDCl3) δ 30.3, 32.7, 96.2, 106.9, 126.4, 126.6, 128.5, 135.3, 202.4.
2-(3-Phenylpropa-1,2-dienyl)naphthalene (3o).20 Following the
typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 3o as a white powder (58 mg, 60%): 1H NMR (400 MHz,
CDCl3) δ 6.58 (d, J = 6.4 Hz, 1H), 6.68 (d, J = 6.4 Hz, 1H), 7.13−7.44
(m, 8H), 7.65−7.71 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 98.6,
98.8, 124.8, 125.8, 125.9, 126.3, 127.0, 127.4, 127.7, 128.4, 128.8 (one
carbon was missed because of overlap), 131.1, 132.8, 133.6, 133.7,
208.4.
1,3-Dimethoxy-5-(3-phenylpropa-1,2-dienyl)benzene (3h). Fol-
lowing the typical procedure above, the crude residue was purified
by column chromatography on silica gel (eluting with petroleum
ether/EtOAc = 30:1) to afford pure 3h as a light yellow oil (56 mg,
56%): 1H NMR (400 MHz, CDCl3) δ 3.69 (s, 6H), 6.28 (t, J = 2.0 Hz,
1H), 6.44−6.46 (m, 3H), 6.51 (d, J = 6.4 Hz, 1H), 7.16 (d, J = 9.1 Hz,
1H), 7.22−7.28 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 55.3, 98.5,
98.6, 99.7, 105.0, 127.0, 127.3, 128.7, 133.5, 135.7, 161.0, 207.9; IR
(film, cm−1) 2962, 1943, 1593, 1455, 1260, 1204, 1154, 1018, 798,
694; EI-MS (m/z, relative intensity) 252 (M+, 100), 237 (35), 221
(30), 207 (40), 178 (30), 165 (65), 115 (25); HRMS (EI) calcd for
C17H17O2 [(M + H)+] 253.1223, found 253.1220.
(3-Cyclohexylpropa-1,2-dienyl)benzene (3p).21 Following the
typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 3p as a colorless oil (38 mg, 48%): 1H NMR (400 MHz, CDCl3)
δ 1.11−1.27 (m, 5H), 1.55−1.78 (m, 5H), 2.05 (s, 1H), 5.49 (t, J = 6.0
Hz, 1H), 6.06−6.08 (m, 1H), 7.09−7.22 (m, 5H); 13C NMR (100
MHz, CDCl3) δ 26.0, 26.1, 33.1, 33.2, 37.6, 95.4, 101.0, 126.4, 126.6,
128.5, 135.2, 204.1.
Ethyl-2-(2-(3-phenylpropa-1,2-dienyl)phenoxy)acetate (3i). Fol-
lowing the typical procedure above, the crude residue was purified by
column chromatography on silica gel (eluting with petroleum ether/
EtOAc = 40:1) to afford pure 3i as a light yellow oil (65 mg, 55%): 1H
NMR (400 MHz, CDCl3) δ 1.22 (t, J = 7.2 Hz, 3H), 4.18 (q, J = 7.2
Hz, 2H), 4.58 (s, 2H), 6.49 (d, J = 6.8 Hz, 1H), 6.70 (d, J = 8.4 Hz,
1H), 6.85 (t, J = 7.2 Hz, 1H), 7.02 (d, J = 6.8 Hz, 1H), 7.06−7.15 (m,
2H), 7.20−7.28 (m, 4H), 7.35 (dd, J = 1.2 and J = 7.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 14.1, 61.3, 66.1, 92.4, 97.9, 112.5, 122.0,
122.8, 126.9, 127.1, 128.2, 128.3, 128.6, 133.8, 154.5, 168.8, 208.3; IR
(film, cm−1) 2963, 1936, 1758, 1493, 1454, 1260, 1200, 1115, 1024,
795, 750, 692; EI-MS (m/z, relative intensity) 294 (M+, 5), 279 (15),
207 (45), 167 (35), 149 (100), 57 (30); HRMS (EI) calcd for
C19H19O3 [(M + H)+] 295.1329, found 295.1328.
Nona-1,2-dienylbenzene (3q).19 Following the typical procedure
above, the crude residue was purified by column chromatography on
silica gel (eluting with petroleum ether) to afford pure 3q as a colorless
oil (56 mg, 70%): 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J = 6.8 Hz,
3H), 1.18−1.32 (m, 6H), 1.35−1.44 (m, 2H), 2.04 (dq, J = 3.0, 7.1
Hz, 2H), 5.48 (q, J = 6.8 Hz,1H), 6.04 (td, J = 2.9, 6.1 Hz, 1H), 7.07−
7.12 (m, 1H), 7.21 (d, J = 4.4 Hz, 4H); 13C NMR (100 MHz, CDCl3)
δ 14.0, 22.6, 28.8, 28.9, 29.1, 31.6, 94.5, 95.1, 126.6, 128.5 (one carbon
was missed because of overlap), 135.2, 205.1.
2-(5-Phenylpenta-3,4-dienyl)naphthalene (3r). Following the
typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
Penta-1,2-diene-1,5-diyldibenzene (3j).16 Following the typical
procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
1
pure 3s as a light yellow oil (73 mg, 68%): H NMR (400 MHz,
1
pure 3j as a light yellow oil (68 mg, 77%): H NMR (400 MHz,
CDCl3) δ 2.44−2.51 (m, 2H), 3.15 (t, J = 7.7 Hz, 2H), 5.55 (dd, J =
6.6, 13.1 Hz, 1H), 6.05 (td, J = 2.8, 6.0 Hz, 1H), 7.04−7.38 (m, 9H),
7.61 (d, J = 7.6 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.92 (d, J = 8.1 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 29.8, 32.5, 94.5, 95.2, 123.7,
125.4, 125.5, 125.8, 126.2, 126.6, 126.7, 126.8, 128.5, 128.7, 131.8,
133.9, 134.8, 137.6, 205.2; IR (film, cm−1) 3060, 2960, 2926, 2852,
1948, 1596, 1494, 1458, 1395, 1260, 1024, 875, 796, 776, 961; EI-MS
(m/z, relative intensity) 270 (M+, 90), 242 (40), 179 (88), 141 (100),
128 (35), 115 (60); HRMS (EI) calcd for C21H19 [(M + H)+]
271.1481, found 271.1480.
CDCl3) δ 2.31−2.40 (m, 2H), 2.67−2.73 (m, 2H), 5.48 (q, J = 8.8 Hz,
1H), 6.02 (td, J = 4.0, 8.0 Hz, 1H), 7.05−7.21 (m, 10H); 13C NMR
(100 MHz, CDCl3) δ 30.5, 35.3, 94.3, 94.9, 125.9, 126.6, 126.7, 128.3,
128.4, 128.5, 134.8, 141.5, 205.2.
1,2-Dichloro-4-(3-phenylpropa-1,2-dienyl)benzene (3k). Follow-
ing the typical procedure above, the crude residue was purified by
column chromatography on silica gel (eluting with petroleum ether) to
afford pure 3k as a light yellow oil (73 mg, 70%): 1H NMR (400 MHz,
CDCl3) δ 6.41 (d, J = 6.4 Hz, 1H), 6.54 (d, J = 6.4 Hz, 1H), (dd, J =
1.6, 8.4 Hz, 1H), 7.15−7.18 (m, 1H), 7.24−7.28 (m, 5H), 7.32 (d, J =
1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 96.8, 99.2, 126.1, 127.1,
127.7, 128.5, 128.8, 130.6, 130.9, 132.7, 132.8, 133.9, 208.1; IR (film,
cm−1) 2917, 1938, 1589, 1473, 1260, 1131, 1029, 887, 823, 696; EI-
MS (m/z, relative intensity) 260 (M+, 35), 225 (100), 189 (55), 94
(20); HRMS (EI) calcd for C15H11Cl2 [(M + H)+] 261.0232, found
261.0231.
1-tert-Butyl-4-(3-phenylpropa-1,2-dienyl)benzene (4a).5d Follow-
ing the typical procedure above, the crude residue was purified by
column chromatography on silica gel (eluting with petroleum ether) to
1
afford pure 4a as a colorless oil (60 mg, 61%): H NMR (400 MHz,
CDCl3) δ 1.23 (s, 9H), 6.50 (s, 2H), 7.16−7.26 (m, 9H); 13C NMR
(100 MHz, CDCl3) δ 31.3, 34.6, 98.1, 98.3, 125.7, 126.7, 127.0, 127.2,
128.7, 130.6, 133.8, 150.5, 207.8.
1-Bromo-4-(3-phenylpropa-1,2-dienyl)benzene (3l).17 Following
the typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 3l as a colorless oil (72 mg, 67%): 1H NMR (400 MHz, CDCl3)
δ 6.46 (d, J = 6.4 Hz, 1H), 6.51 (d, J = 6.4 Hz, 1H), 7.12−7.17 (m,
3H), 7.22−7.29 (m, 4H), 7.35 (d, J = 8.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 97.6, 98.8, 121.0, 127.0, 127.5, 128.5, 128.8, 131.8,
132.6, 133.1, 207.9.
1-(4,4-Dimethylpenta-1,2-dienyl)-3-methylbenzene (4b). Follow-
ing the typical procedure above, the crude residue was purified by
column chromatography on silica gel (eluting with petroleum ether) to
1
afford pure 4b as a colorless oil (31 mg, 42%): H NMR (400 MHz,
CDCl3) δ 1.05 (s, 9H), 2.25 (s, 3H), 5.48 (d, J = 6.4 Hz, 1H), 6.08 (d,
J = 6.4 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 7.02 (d, J = 6.0 Hz, 2H),
7.09−7.16 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 21.4, 30.3, 32.7,
96.2, 106.8, 123.5, 127.1, 127.4, 128.4, 135.2, 138.1, 202.4; IR (film,
cm−1) 2960, 2865, 1948, 1604, 1459, 1362, 1251, 1190, 903, 880, 792,
690; EI-MS (m/z, relative intensity) 186 (M+, 65), 171 (35), 156 (20),
130 (70), 57 (100); HRMS (EI) calcd for C14H19 [(M + H)+]
187.1481, found 187.1482.
1-(3-Phenylpropa-1,2-dienyl)-4-(trifluoromethyl)benzene
(4c).5d,22 Following the typical procedure above, the crude residue was
purified by column chromatography on silica gel (eluting with
petroleum ether) to afford pure 4c as a colorless oil (68 mg, 65%): 1H
NMR (400 MHz, CDCl3) δ 6.54 (dd, J = 7.4, 17.5 Hz, 2H), 7.09−7.18
(m, 4H), 7.23−7.25 (m, 3H), 7.34 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.0
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 97.6, 99.0, 124.2 (q, J =
1-Fluoro-4-(3-phenylpropa-1,2-dienyl)benzene (3m).18 Following
the typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 3m as a colorless oil (55 mg, 66%): 1H NMR (400 MHz, CDCl3)
δ 6.50 (q, J = 6.5 Hz, 2H), 6.92 (t, J = 8.0 Hz, 2H), 7.13−7.16 (m,
1H), 7.21−7.27 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 97.4, 98.6,
115.7 (d, J = 21.6 Hz), 127.0, 127.4, 128.6 (d, J = 37.3 Hz), 129.1,
129.5 (d, J = 3.4 Hz), 133.4, 162.1 (d, J = 245.1 Hz), 207.5.
(4,4-Dimethylpenta-1,2-dienyl)benzene (3n).19 Following the
typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 3n as a colorless oil (59 mg, 85%): 1H NMR (400 MHz, CDCl3)
D
dx.doi.org/10.1021/jo3024686 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
270.1 Hz), 125.6 (q, J = 3.8 Hz), 127.7, 128.2, 128.8, 129.2 (q, J = 32.2
Hz), 130.2, 132.8, 137.6 (d, J = 1.2 Hz), 208.7.
nitrogen. Then phenylacetylene 2a (40.8 mg, 0.4 mmol) was added.
The resulting mixture was stirred at 90 °C for 1 h. After cooling to
room temperature, the mixture was filtered through a short silica gel
column eluting with EtOAc. The solvent was removed under vacuum,
and the crude residue was purified by column chromatography on
silica gel eluting with petroleum ether to afford pure (4,4-
dimethylpenta-1,2-dienyl)benzene 3n as a colorless oil (70 mg, 94%).
Hepta-1,2-dienylbenzene (4d).19 Following the typical procedure
above, the crude residue was purified by column chromatography on
silica gel (eluting with petroleum ether) to afford pure 4d as a colorless
oil (45 mg, 66%): 1H NMR (400 MHz, CDCl3) δ 0.84 (t, J = 7.2 Hz,
3H), 1.29−1.46 (m, 4H), 2.06 (dq, J = 3.0, 7.2 Hz, 2H), 5.49 (q, J =
6.8 Hz, 1H), 6.04 (td, J = 3.0, 6.2 Hz, 1H), 7.09−7.12 (m, 1H), 7.21
(d, J = 4.4, Hz, 4H); 13C NMR (100 MHz, CDCl3) δ 13.9, 22.2, 28.4,
31.3, 94.5, 95.1, 126.5, 126.6, 128.5, 135.1, 205.1.
ASSOCIATED CONTENT
■
S
* Supporting Information
Nona-3,4-dienylbenzene (4e).20 Following the typical procedure
above, the crude residue was purified by column chromatography on
silica gel (eluting with petroleum ether) to afford pure 4e as a colorless
oil (74 mg, 93%): 1H NMR (400 MHz, CDCl3) δ 0.81 (t, J = 6.8 Hz,
3H), 1.23−1.28 (m, 4H), 1.84−1.90 (m, 2H), 2.19−2.25 (m, 2H),
2.64 (t, J = 7.8 Hz, 2H), 4.97−5.07 (m, 2H), 7.07−7.21 (m, 5H); 13C
NMR (100 MHz, CDCl3) δ 13.9, 22.1, 28.6, 30.7, 31.3, 35.5, 90.2,
91.5, 125.7, 128.2, 128.5, 141.9, 204.0.
1
Copies of H and 13C spectra for all products. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: wangjb@pku.edu.cn.
■
(6,6-Dimethylhepta-3,4-dienyl)benzene (4f).21 Following the
typical procedure above, the crude residue was purified by column
chromatography on silica gel (eluting with petroleum ether) to afford
pure 4f as a colorless oil (71 mg, 89%): 1H NMR (400 MHz, CDCl3)
δ 0.93 (s, 9H), 2.20−2.26 (m, 2H), 2.63 (t, J = 8.0 Hz, 2H), 5.03 (td, J
= 3.0, 6.3 Hz, 1H), 5.12 (q, J = 6.3 Hz, 1H), 7.07−7.21 (m, 5H); 13C
NMR (100 MHz, CDCl3) δ 30.2, 30.9, 31.7, 35.5, 92.1, 103.5, 125.8,
128.3, 128.5, 142.0, 201.1.
3-(3-(Naphthalen-2-yl)propa-1,2-dienyl)thiophene (4g). Follow-
ing the typical procedure above, the crude residue was purified by
column chromatography on silica gel (eluting with petroleum ether/
EtOAc = 100:1) to afford pure 4g as a colorless oil (57 mg, 58%): 1H
NMR (400 MHz, CDCl3) δ 6.61 (dd, J = 6.4, 14.4 Hz, 1H), 6.74 (s,
1H), 7.02−7.16 (m, 2H), 7.27−7.33 (m, 3H), 7.47 (dd, J = 8.5, 41.1
Hz, 1H), 7.60−7.68 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 93.1,
98.0, 121.5, 124.8, 125.8, 125.9, 126.0, 126.4, 127.0, 127.5, 127.6,
127.7, 128.0, 128.1, 128.4, 130.5, 208.6; IR (film, cm−1) 3054, 2959,
2925, 1936, 1597, 1505, 1377, 1260, 1018, 650, 905, 794, 731; EI-MS
(m/z, relative intensity) 248 (M+, 35), 207 (100), 133 (8), 96 (10), 59
(12); HRMS (EI) calcd for C17H13S [(M + H)+] 249.0732, found
249.0731.
Author Contributions
§These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The project is supported by National Basic Research Program
(973 Program, No. 2009CB825300), Natural Science Founda-
tion of China (21272010).
REFERENCES
■
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Typical Procedure for Gram-Scale Experiments. Under a
nitrogen atmosphere, 1-hexyne 2e (820 mg, 10 mmol) was added to a
mixture of CuI (382 mg, 2.0 mmol), LitOBu (2.8 g, 35 mmol), and N-
tosylhydrazones 1j (6.65 g, 22 mmol) in dioxane (100 mL). The
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purified by silica gel column chromatography using petroleum ether as
an eluting solvent to afford pure nona-3,4-dienylbenzene 4e as
colorless oil (1.7 g, 85%).
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dx.doi.org/10.1021/jo3024686 | J. Org. Chem. XXXX, XXX, XXX−XXX