Synthesis of 1-aryl-1,3-diyne and 2-aryl-1,1-dialkynylethene from the Sonogashira reactions of 2-aryl-1,1-dibromoethene

Article abstract of DOI:10.1016/S0040-4020(01)00829-8

Both 1-aryl-1,3-diyne and 2-aryl-1,1-dialkynylethene were produced from the Sonogashira reactions of 2-aryl-1,1-dibromoethene with 1-alkyne. The ratio of the products varied according to the reaction conditions. The coupling reactions in benzene afforded

Full text of DOI:10.1016/S0040-4020(01)00829-8

TETRAHEDRON
Pergamon
Tetrahedron 57 42001) 8283±8290
Synthesis of 1-aryl-1,3-diyne and 2-aryl-1,1-dialkynylethene
from the Sonogashira reactions of 2-aryl-1,1-dibromoethene
Hee Bong Lee, Dal Ho Huh, Joon Seok Oh, Gwan-Hong Min, Byung Hyun Kim, Dong Hwal Lee,
Jae Kwang Hwang and Young Gyu Kimp
School of Chemical Engineering, College of Engineering, Seoul National University, Seoul 151-744, South Korea
Received 5 September 2000; accepted 8 August 2001
AbstractÐBoth 1-aryl-1,3-diyne and 2-aryl-1,1-dialkynylethene were produced from the Sonogashira reactions of 2-aryl-1,1-dibromo-
ethene with 1-alkyne. The ratio of the products varied according to the reaction conditions. The coupling reactions in benzene afforded the
2-aryl-1,1-dialkynylethene as a major product and no 1-aryl-1,3-diyne was isolated. The 1-aryl-1,3-diyne could be obtained in DMF in
acceptable yields. When amines were used as a reaction solvent, the coupling reaction gave the 2-aryl-1,1-dialkynylethene 420%) and the
conjugated enyne 468%) in diisopropylamine, whereas only the 1-aryl-1,3-diyne was isolated in piperidine in 56% yield. q 2001 Elsevier
Science Ltd. All rights reserved.
1. Introduction
easier to determine the degree of branching of 2 just by
titration of the acidic groups.
As part of a research program directed toward the synthesis
of hyperbranched polymers with electroluminescent proper-
ties, a novel AB2 type monomer 1 with a carboxylic acid end
group4R ˆH) was designed to overcome the low yield and
the low molecular weight of the polymer product 2 as
reported in the previous study 4Fig. 1).1 It would be much
However, an unexpected 1,3-diyne 4 was obtained as a
minor product after puri®cation2 when the cross-coupling
reaction of dibromide 3 with 10-undecynoate was carried
out to give the desired monomer, 2-aryl-1,1-dialkynylethene
1, under the typical Sonogashira reaction conditions
Figure 1. Structures of monomer 1 and polymer 2.
Scheme 1. Results from the initial Sonogashira reaction.
Keywords: coupling reactions; diyne; enyne; palladium and compounds.
Corresponding author. Tel.: 182-2-880-8347, Fax: 182-2-885-6989; e-mail: ygkim@plaza.snu.ac.kr
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020401)00829-8

8284
H. B. Lee et al. / Tetrahedron 57 &2001) 8283±8290
Scheme 2. The model Sonogashira reactions in the present study. See Experimental and the corresponding Tables for the detailed reaction conditions.
ture to 3, and commercially available 3-butyn-1-ol 46) were
Table 1. Effect of the solvents on the Sonogashira reactions.
chosen as model substrates to reduce complex side
reactions and for simple workup. Dibromide 5 was
ef®ciently prepared from the Heck reaction of 4-bromo-
benzaldehyde with styrene followed by the Wittig-type
dibromoole®nation reaction7 as described in the previous
report 4see Experimental).1 The standard Pd-catalyzed
cross-coupling reaction between 5 and 6 is shown in
Scheme 2 and the detailed reaction conditions are shown
in the corresponding table.
entry time 4h) solvent
5
yield 4%)
4% recovery)
7
8
9
1
5
2
0.7
20
4
PhCH3
benzene
benzene
ClCH2CH2Cl 18
THF
±
±
±
37
60
75
42
40
28
10
48
±
±
±
8
6
32
50
15
±
10
27
43
±
18
±
±
±
±
±
±
±
±
±
9
32
58
43
62
15
28
2
3a
4
5
±
±
60
22
45
±
6
7
8
9
5
EtOAc
acetone
CH3CN
DMF
DMF
DMF
DMSO
NMP
butanol
20
10
13
3.5
2
20
20
6
First, various solvents with different polarity were examined
under the reaction conditions as shown in Table 1. The
results indicate that the polarity of the solvents has a signi®-
cant effect on the reaction products. The reaction in the
solvents of low polarity afforded the monosubstituted conju-
gated enyne 8 as well as the desired disubstituted 2-aryl-1,1-
dialkynylethene 7. However, 1-aryl-1,3-diyne 9 was
isolated as a major product in highly polar solvents such
as DMF or DMSO. The yield of 9 was improved to 58%
by reacting at 708C 4entry 10). No reaction occurred in
HMPA 4not shown). The similar dependence of the products
on the polarity of solvents was also described in the
Stille reactions of the 1,1-dibromo-1-alkenes with organo-
stannanes.6a
10b
11c
12
13
14b
±
±
±
±
±
11
62
±
Reaction conditions: 5 40.5 mmol), 6 42.2 equiv.), PdCl24PPh3)2 410 mol%),
PPh3 420 mol%), CuI 420 mol%), TEA 44 equiv.), solvent 420 mL) at room
temperature.
a
4.4 equiv. of alkyne 6 was used in 5 mL of benzene.
Reacted at 708C.
Reacted at 1008C.
b
c
4Scheme 1).3 Because few studies have been reported on the
formation of 1,3-diynes from the Sonogashira reactions of
1,1-dihaloalkenes,4 we have systematically investigated the
Sonogashira cross-coupling reaction conditions of 2-aryl-
1,1-dibromoethene with 1-alkyne,5,6 and report the results
as follows.
The coupling reactions in the present study gave invariably
the conjugated diyne byproduct, 3,5-octadiyne-1,8-diol,
obtained from the homocoupling of 6 in about 10±15%
yield of the amount of 6 used, whose yields are not included
in Table 1 and the following Tables 2±6.
The ratio of the 4E)- and 4Z)-isomers of 8 was between about
1:2 and 1:4 in other solvents than benzene and toluene,
where the 4Z)-isomer of 8 was exclusively obtained. The
stereochemistry of the 4Z)-isomer was determined by the
2. Results and Discussion
2-44E)-4-Stilbenyl)-1,1-dibromoethene 45), similar in struc-
Table 2. Effect of the amine solvents on the Sonogashira reactions.
entry
amine
6
time
4h)
5
yield 4%)
45 mL)
4equiv.)
4% recovery)
7
8
9
1
2
3
4
piperidine
pyrrolidine
pyrrolidine
morpholine
diisopropylamine
diisopropylamine
diisopropylamine
diethylamine
isopropylamine
t-butylamine
butylamine
2.2
2.2
2.2
2.2
2.2
4.4
5.5
2.2
2.2
2.2
2.2
24
7
24
20
8
8
8
20
12
7
±
48
±
77
5
±
±
±
±
±
20
65
61
±
±
32
±
±
±
±
±
68
5
±
15
±
7
±
56
20
10
12
±
±
±
15
37
36
40
5
6
7a
8
±
59
55
±
9
10
11b
20
±
Reaction conditions: 5 40.5 mmol), 6, PdCl24PPh3)2 410 mol%), PPh3 420 mol%), CuI 420 mol%), amine 45 mL) at room temperature.
Pd24dba)3 410 mol%) was used.
5 mL of DMF was added because no conversion to the expected products was observed even after 20 h in butylamine only.
a
b

H. B. Lee et al. / Tetrahedron 57 &2001) 8283±8290
Table 3. Effect of the palladium reagents on the Sonogashira reactions.
8285
entry
Pd reagents 410 mol%)
time 4h)
6 4equiv.)
solvent
5 4% recovery)
yield 4%)
7
8
9
1
2
3
4
5
6
7
8
PdCl24PPh3)2
Pd24dba)3
Pd4OAc)2
PdCl24PhCN)2
PdCl2
Pd4PPh3)4
PdCl24PPh3)2
Pd24dba)3
Pd4OAc)2
PdCl24PhCN)2
PdCl2
2
2.5
3
3
6
22
10
4
20
10
24
20
3.3
3.3
3.3
3.3
3.3
3.3
2.2
2.2
2.2
2.2
2.2
2.2
benzene
benzene
benzene
benzene
benzene
benzene
DMF
DMF
DMF
DMF
DMF
DMF
±
±
±
±
±
±
45
10
±
72
31
78
70
56
61
54
50
59
±
5
7
±
±
±
±
5
7
8
16
±
±
±
±
±
±
±
±
±
±
±
±
32
50
40
23
45
10
9
10a
11
12
Pd4PPh3)4
±
Reaction conditions: 5 40.5 mmol), 6, Pd reagent 410 mol%), PPh3 420 mol%), CuI 420 mol%), TEA 44 equiv.), solvent 420 mL) at room temperature.
5 mol% of PdCl24PhCN)2 was used.
a
metal±halogen exchange of the 4Z)-isomer of 8 at 2788C
affording ole®n 10 in 89% yield 4Scheme 3). The coupling
constants of the exchanged proton in 10, 16.3 and 2.1 Hz,
indicate the typical 4E)-ole®nic and propargylic coupling,
respectively. The con®gurational stability of the alkenyl-
lithium intermediate has been demonstrated in the litera-
ture.8
The nature of amines is critical to determine the reaction
products. 1,3-Diyne 9 was isolated as the only product in
cyclic secondary amines, isopropyl amine, and butylamine
4entries 1±4, 9 and 11). The highest yield 456%) was
realized with piperidine whereas the more yield of the
1,3-diyne 472%) was resulted from the initial Sonogashira
reaction of 3 and TBS-protected 10-undecyn-1-ol under the
similar reaction conditions. However, the reactions in
4i-Pr)2NH produced both 7 and 8, but we could not isolate
9. The yield of 7 was increased to 65% using excess of 6
4entry 6). The enyne products, 7 and 8, were produced
Next, the impact of amine bases was investigated as
reported by Alami and coworkers9 and the results are listed
in Table 2. The amines were used here as a reaction solvent.
Table 4. Effect of the phosphine ligands on the Sonogashira reactions.
entry
ligands
time 4h)
6 4equiv.)
solvent
5 4% recovery)
yield 4%)
7
8
9
1
2
3
4
5
6
PPh3
TFP
P4o-Tol)3
dppb
P4p-MeOPh)3
PPh3
TFP
2
2.5
2
20
2.5
4
2
4
6
24
6
3.3
3.3
3.3
3.3
3.3
2.2
2.2
2.2
2.2
2.2
2.2
benzene
benzene
benzene
benzene
benzene
DMF
DMF
DMF
DMF
DMF
DMF
±
±
9
92
29
10
±
±
±
70
82
40
±
31
5
5
30
±
±
6
13
5
12
±
±
8
±
±
±
±
±
±
±
±
50
45
41
52
15
40
7
8a
9
TFP
P4o-Tol)3
dppb
P4p-MeOPh)3
10
11
54
±
±
10
Reaction conditions: 5 40.5 mmol), 6, PdCl24PPh3)2 in PhH or Pd24dba)3 in DMF 410 mol%), phosphine ligand 420 mol%), CuI 420 mol%), TEA 44 equiv.),
solvent 420 mL) at room temperature.
2 mol% of Pd24dba)3 was used.
a
Table 5. Effect of the amount of the Pd catalysts on the Sonogashira reactions.
entry
Pd reagents 4mol%)
6 4equiv.)
time 4h)
solvent
5 4% recovery)
yield 4%)
7
8
9
1
2
3
4
5
6
PdCl24PPh3)2 410)
PdCl24PPh3)2 42)
PdCl24PPh3)2 41)
Pd24dba)3 410)
Pd24dba)3 42)
3.3
3.3
3.3
2.2
2.2
2.2
2
5
5
4
17
17
benzene
benzene
benzene
DMF
DMF
DMF
±
6
±
10
58
73
82
61
63
5
±
±
6
±
±
±
50
16
6
25
25
±
±
±
Pd24dba)3 41)
Reaction conditions: 5 40.5 mmol), 6, Pd reagent, PPh3 420 mol%), CuI 420 mol%), TEA 44 equiv.), solvent 420 mL) at room temperature.

8286
H. B. Lee et al. / Tetrahedron 57 &2001) 8283±8290
Table 6. Effect of the reaction concentration on the Sonogashira reactions.
entry
conc. 4mM)
ligand
6 4equiv.)
time 4h)
solvent
5 4% recovery)
yield 4%)
7
8
9
1
2
3
4
25
50
100
200
25
25
50
100
200
200
TFP
TFP
TFP
TFP
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
3.3
3.3
3.3
3.3
2.2
2.2
2.2
2.2
2.2
2.2
2
benzene
benzene
benzene
benzene
DMF
DMF
DMF
DMF
DMF
DMF
±
±
±
82
79
80
82
5
6
5
6
5
±
±
±
±
±
±
±
±
±
±
50
37
46
33
20
44
1.5
1.5
1
±
5
4
10
31
±
±
±
6a
7
20
2.5
1.5
1.0
3.0
3
21
32
32
20
8
9
10a
±
Reaction conditions: 5 40.5 mmol), 6, PdCl24PPh3)2 in PhH or Pd24dba)3 in DMF 410 mol%), PPh3 420 mol%), CuI 420 mol%), TEA 44 equiv.), solvent 420±
2.5 mL) at room temperature.
Piperidine was used instead of TEA.
a
preferentially in the bulky amines whereas the 1,3-diyne
product 9 was more favored in the amines of relatively
small size.
ligands for the formation of the enynes from the Stille
coupling reactions of the 1,1-dibromo-1-alkenes.
Reduction in the amount of the palladium catalyst decreased
the rate and yields of the coupling reactions 4Table 5).
More signi®cant decrease was observed with the Pd24dba)3
catalyst.
Six palladium catalysts were then tested in either benzene or
DMF to optimize the conditions for either 7 or 9, respec-
tively. The results are summarized in Table 3. In benzene,
most of the Pd reagents catalyzed effectively the coupling
reactions to give 7 as a major product. However, Pd24dba)3
was the most ef®cient catalyst in DMF in terms of the yield
and reaction rate for 9 4entry 8).
Increase of the reaction concentration in benzene acceler-
ated the reaction rate but did not affect the yields of the
enyne products much 4Table 6, entries 1±4). However, a
signi®cant amount of 7 was produced in addition to 9 at
the higher concentrations in DMF 4entries 7±10). The
concentration of the reaction mixture was controlled by
reducing the amount of the reaction solvent.
The phosphine ligands were also examined with 10 mol% of
PdCl24PPh3)2 in benzene or with 10 mol% of Pd24dba)3 in
DMF at room temperature, respectively 4Table 4). Tri-2-
furylphosphine 4TFP)10 and PPh3 enhanced the coupling
reactions effectively in both solvents, whereas the dppb
and P4p-MeOPh)3 ligands were less ef®cient. The present
results are in contrast to those reported by Shen and Wang.6a
They reported that P4p-MeOPh)3 was one of the effective
The dependence of the products on the polarity of solvents
in the Sonogashira reactions 4Table 1) could be explained
by the working hypothesis shown in Scheme 4 that is
analogous to that proposed by Shen and Wang.6a The
Scheme 3. Determination of stereochemistry for 4Z)-8 by metal±halogen exchange.
Scheme 4. Possible reaction pathways for the products in the present study.

H. B. Lee et al. / Tetrahedron 57 &2001) 8283±8290
8287
Scheme 5. Conversion studies of 8.
Scheme 6. Formation of the byproduct 14 in pyrrolidine as a reaction solvent.
usual cross-coupling reaction is favored in nonpolar
solvents such as benzene or toluene to give 7 or 8 after
the oxidative addition of Pd40) 4path A). The highly polar
and good coordinating solvents such as DMF or DMSO
would favor the solvated ionic complex 12 that is converted
into the alkynyl palladium intermediate 13 4path B).
a reaction solvent, albeit in poor yield. The major product in
the above reduction reaction, however, was a stereoisomeric
mixture of vinyl bromide 17 456%, 4Z):4E)ˆ,4.5:1). An
authentic sample of alkyne 16 was obtained independently
in high yield 490%) by treating 5 with BuLi as reported in
the literature 4see Experimental).11 The similar reduction
reaction with Bu3SnH in DMF produced, instead, only 17
in high yield 44Z):4E)ˆ,13:1), which seems comple-
mentary to the results reported by Uenishi and coworkers.12
Although they had the exclusive 4Z)-selectivity in several
common organic solvents, the low stereoselectivity
44Z):4E)ˆ,2:1) was observed in polar solvents such as
EtOH or AcOH with no co-solvent. The conjugated diyne
18 was also prepared by coupling of 15 with 16 in order to
show whether 18 is produced as a byproduct in the above
cross-coupling reaction studies or not. No signi®cant
amount of 18 was observed in the cross-coupling reactions
reported. A blank test with 5 under the similar conditions
[10% Pd24dba)3, 20% CuI, 20% PPh3, TEA 44 equiv.),
DMF, rt, 24 h] resulted in only a trace of 18 4,2%) and
most of 5 was recovered.
The effect of the amines also supports the possible presence
of the intermediate 12 that we could not isolate. Better
coordinating amines of small size would favor the preferen-
tial formation 12 leading eventually to 9, whereas poor
coordinating amines of large size produced only the enyne
products 7 and 8 4entries 5 versus 9, Table 2). The amines of
intermediate size gave both products 4entries 8 and 10,
Table 2). At higher concentration, therefore, both reaction
pathways compete even in DMF 4entries 7±10, Table 6).
Alternative pathway to give 9 directly from 8 by dehydro-
bromination was tested by treating 8 without 6 under other-
wise the same reaction conditions 4Scheme 5). No expected
reaction occurred and most of the starting material was
recovered. The similar result has been also reported.6a
Addition of 6 to the above reaction, however, produced 7
in quantitative yield. The poor yield with pyrrolidine 4entry
3, Table 2) seems in part due to the byproduct 14 that
contains the pyrrolidine unit 4Scheme 6). We could obtain
14 in 68% yield without using CuI. We are currently investi-
gating the mechanism and utility of this side reaction, and
will report the results in due course.
3. Conclusions
We have established that the Sonogashira reactions of
2-aryl-1,1-dibromoethene 5 with 1-alkyne 6 produce the
different products depending on the reaction conditions.
Both the solvent polarity and the nature of amines used as
a reaction solvent have a signi®cant impact on the product
ratio. The alkynyl palladium species 13 seemed to be a
possible reaction intermediate for the formation of 1-aryl-
1,3-diyne 9. The result of dependence on the reaction con-
ditions of widely used Sonogashira cross-coupling reactions
should be useful for the preparation of these important
classes of compounds such as 2-aryl-1,1-dialkynylethenes13
In an effort to support that the alkynyl palladium species 13
is a plausible reaction intermediate, we have synthesized 9
independently from the coupling reaction between alkynyl
bromide 15, derived from 5, and alkyne 6 in the presence of
Pd24dba)3 4Scheme 7). We could also produce a terminal
alkyne 16 by reduction with Bu3SnH using pyrrolidine as
Scheme 7. Correlation studies.

8288
H. B. Lee et al. / Tetrahedron 57 &2001) 8283±8290
and 1-aryl-1,3-diynes.14 Particularly, the mild reaction
conditions like ambient temperature could tolerate a wide
range of functional groups present in the starting materials.
In addition, 2-aryl-1,1-dibromoethene can be considered as
a synthetic equivalent to 2-aryl-1-bromoacetylene under the
reaction conditions employed.
4M114, 49), 364 4M112, 100), 362 4M1, 51), 284 44),
202 491), 101 447); HRMS 4EI) calcd for C16H12Br2
363.9285 4M112), found 363.9290.
4.3. Procedure for the standard Sonogashira reactions
To a solution of dibromide 5 4184 mg, 0.500 mmol), palla-
dium reagent 40.0500 mmol), phosphine ligand 40.100
mmol), and CuI 419.5 mg, 0.100 mmol) in solvent 420
mL) at room temperature were added amine reagent 42.00
mmol) and 3-butyn-1-ol 46) 478.0 mg, 1.10 mmol) under N2
atmosphere. After the time indicated in Tables 1±6,
saturated aq. NH4Cl 420 mL) was added to the reaction
mixture and the resulting mixture was extracted with chloro-
form 43£10 mL). The combined organic layers were washed
with water 43£20 mL) and brine 43£5 mL), dried with
anhydrous MgSO4, ®ltered, and concentrated under reduced
pressure. The crude product was puri®ed by ¯ash column
chromatography to give recovered dibromide 5, 2-aryl-1,1-
dialkynylethene 7, conjugated enyne 8, and 1-aryl-1,3-diyne
9 as a yellowish solid. The isolated yields are shown in the
Tables. The inseparable products 8 and 9 were isolated as a
4. Experimental
4.1. General Methods
Materials were obtained from commercial suppliers and
were used without further puri®cation. For anhydrous
solvents, CH2Cl2 was distilled from calcium hydride.
Diethyl ether, THF, benzene, and toluene were distilled
from sodium/benzophenone. All glassware, syringes,
needles, and magnetic bars used in the moisture-sensitive
reactions were oven-dried at 1208C for at least 4 h and
stored in dessicator until use. Upon workup, solvent was
removed with a rotary evaporator and then with a high
vacuum pump. Reactions were monitored by TLC.
1
Commercially available TLC plates 4Silica gel 60 F254
,
mixture and the ratio of 8 to 9 was based on the H NMR
Merck) were visualized under UV light 4254 or 365 nm)
followed by molybdophosphoric acid staining. Dry-column
¯ash chromatography was done on silica gel 60G 4particle
size 5-40 mm, Merck). IR spectra were recorded with a
integration of the isolated mixture. The conjugated diyne
byproduct, 3,5-octadiyne-1,8-diol, obtained from the homo-
coupling of 6 was always obtained in about 10-15% yield of
the amount of 6 used and their yields are not included in
Tables 1±6.
1
JASCO model FT-IR 200. H NMR and 13C NMR spectra
were measured in CDCl3 at 300 MHz and 75 MHz 4JEOL
JNM-LA 300), respectively. Multiplicity was denoted by s
4singlet), d 4doublet), t 4triplet), q 4quartet), m 4multiplet).
Coupling constants 4J) were in hertz 4Hz).
4.3.1. 5-..E)-4-Styrenylbenzylidene)nona-3,6-diyne-1,9-
diol .7). The analytical sample was recrystallized from
chloroform to yield pure 7 as a golden solid: Rfˆ0.3
4EtOAc: hexaneˆ2:1); mp149-150 8C; IR 4KBr) 3343,
3025, 2946, 2214, 1056, 971, 895, 817, 754, 691, 540
4.2. 2-..E)-4-Stilbenyl)-1,1-dibromoethene .5)
1
cm21; H NMR d 7.82 4d, 2H, Jˆ8.2), 7.48-7.53 4m, 4H),
To a solution of 4-bromobenzaldehyde 43.70 g, 20.0 mmol),
Pd4OAc)2 40.225 g, 1.00 mmol), and P4o-Tol)3 40.609 g,
2.00 mmol) in DMF 4120 mL) at room temperature were
added styrene 42.80 mL, 24.0 mmol) and triethylamine
48.40 mL, 60.0 mmol) under N2 atmosphere and the result-
ing mixture was heated for 30 h at 1008C in an oil bath.
After the reaction mixture was cooled to room temperature,
water 4240 mL) was added and the resulting mixture was
extracted with chloroform 43£120 mL). The combined
organic layers were washed with water 43£200 mL) and
brine 43£30 mL), dried with anhydrous MgSO4, and
concentrated under reduced pressure after ®ltration. The
crude product was chromatographed 4CHCl3) to give
3.98 g 4quantitative) of 4E)-4-stilbenecarboxaldehyde with
a small amount of impurity. Without further puri®cation,
this mixture was added to a solution of CBr4 49.95 g,
30.0 mmol) and PPh3 415.7 g, 60.0 mmol) in CH2Cl2
4120 mL) at 08C under N2 atmosphere. After stirring for
2 h at 08C, the reaction mixture was concentrated and the
residue was washed with methanol 43£100 mL). The crude
product was recrystallized from ethyl acetate 4100 mL) to
give 5.53 g 476% from 4-bromobenzaldehyde) of pure 5 as a
pale yellowish crystal: Rfˆ0.6 4CHCl3:hexaneˆ1:2); mp
139-1408C; IR 4KBr) 3022, 972, 879, 817, 756, 693,
7.37 4t, 2H, Jˆ7.4), 7.25-7.29 4m, 1H), 7.16 4d, 1H, Jˆ
16.3), 7.08 4d, 1H, Jˆ16.3), 6.96 4s, 1H), 3.85 4q, 2H, Jˆ
6.2), 3.80 4q, 2H, Jˆ6.2), 2.75 4t, 2H, Jˆ6.2), 2.66 4t, 2H,
Jˆ6.2), 1.87 4t, 2H, Jˆ6.2); 13C NMR d 142.2, 137.9,
137.1, 134.9, 129.5, 129.0, 128.7, 128.0, 127.8, 126.6,
126.4, 102.6, 92.8, 85.5, 82.7, 80.3, 61.0, 60.9, 24.3, 23.9;
MS 4EI) m/z 4%): 342 4M1, 100), 311 46), 265 421), 252
417); HRMS 4EI) calcd for C24H22O2 342.1620, found
342.1624.
4.3.2. .Z)-5-Bromo-6-..E)-4-stilbenyl)hex-5-en-3-yn-1-ol
..Z)-8). The analytical sample was recrystallized from
hexane and ethyl acetate to yield pure 4Z)-8 as a tarnished
yellow solid: Rfˆ0.6 4EtOAc:hexaneˆ2:1); mp145-147 8C
4dec.); IR 4KBr) 3376, 3024, 2944, 2215, 1049, 970, 964,
1
880, 814, 751, 691, 539 cm21; H NMR d 7.69 4d, 2H,
Jˆ8.3), 7.50-7.54 4m, 4H), 7.26-7.40 4m, 3H), 7.19 4s,
1H), 7.17 4d, 1H, Jˆ16.3), 7.08 4d, 1H, Jˆ16.3), 3.82 4q,
2H, Jˆ6.2), 2.74 4t, 2H, Jˆ6.2), 1.77 4t, 1H, Jˆ6.2); 13C
NMR d 137.8, 137.1, 135.7, 134.0, 129.7, 129.6, 128.7,
128.0, 127.9, 126.6, 126.3, 99.9, 89.4, 82.8, 60.9, 23.9;
MS 4EI) m/z 4%): 354 4M112, 99), 352 4M1, 100), 272
414), 241 465); HRMS 4EI) calcd for C20H17OBr 352.0463
4M1), found 352.0449.
1
542 cm21; H NMR d 7.48-7.58 4m, 7H), 7.26-7.40 4m,
3H), 7.17 4d, 1H, Jˆ16.4), 7.08 4d, 1H, Jˆ16.4); 13C
NMR d 137.7, 137.2, 136.6, 134.4, 129.8, 128.8, 128.7,
128.0, 127.9, 126.6, 126.5, 89.3; MS 4EI) m/z 4%): 366
4.3.3. 6-..E)-4-Stilbenyl)hexa-3,5-diyn-1-ol .9). The ana-
lytical sample was recrystallized from hexane and ethyl
acetate to yield pure 9 as a tarnished yellow solid: Rfˆ0.6

H. B. Lee et al. / Tetrahedron 57 &2001) 8283±8290
8289
4EtOAc:hexaneˆ2:1); mp137-139 8C 4dec.); IR 4KBr)
3348, 3024, 2948, 2241, 1039, 971, 824, 752, 691,
41.0 M solution in THF, 0.360 mmol) under N2 atmosphere.
After stirring for 2 h at 2788C, saturated aq. NH4Cl 420 mL)
was added and the resulting mixture was extracted with
chloroform 43£20 mL). The combined organic layers were
washed with water 43£20 mL) and brine 43£5 mL), dried
with anhydrous MgSO4, ®ltered, and concentrated under
reduced pressure. The crude product was puri®ed by ¯ash
column chromatography to give 82.0 mg 495%) of alkynyl
bromide 15 as a yellowish solid. The analytical sample was
recrystallized from hexane to yield pure 15: Rfˆ0.6
4CHCl3:hexaneˆ1:2); mp120 8C; IR 4KBr) 3026, 2193,
9H), 7.14 4d, 1H, Jˆ16.3), 7.06 4d, 1H, Jˆ16.3); 13C
NMR d 137.7, 136.9, 132.3, 129.9, 128.7, 127.9, 127.7,
126.6, 126.3, 121.6, 80.2, 50.5; MS 4EI) m/z 4%): 284
4M112, 58), 282 4M1, 59), 202 4100), 101 423); HRMS
4EI) calcd for C16H11Br 282.0044, found 282.0053.
1
545 cm21; H NMR d 7.46-7.53 4m, 6H), 7.26-7.40 4m,
3H), 7.14 4d, 1H, Jˆ16.3), 7.06 4d, 1H, Jˆ16.3), 3.81 4q,
2H, Jˆ6.2), 2.66 4t, 2H, Jˆ6.2), 1.76 4t, 1H, Jˆ6.2); 13C
NMR d 138.1, 136.9, 132.9, 130.1, 128.7, 128.0, 127.7,
126.6, 126.4, 120.6, 81.5, 75.6, 74.8, 67.0, 60.8, 24.0; MS
4EI) m/z 4%): 272 4M1, 100), 241 476); HRMS 4EI) calcd for
C20H16O 272.1202, found 272.1201.
4.4. .E)-6-..E)-4-Stilbenyl)hex-5-en-3-yn-1-ol .10)
1
971, 823, 754, 690, 544 cm21; H NMR d 7.26-7.53 4m,
To a solution of the 4Z)-isomer of 8 4100 mg, 0.280 mmol)
in THF 410 mL) at 2788C was added slowly 0.9 mL of BuLi
41.6 M solution in hexane, 1.44 mmol) under N2 atmos-
phere. After stirring for 10 min at 2788C, addition of excess
methanol 45 mL) was followed by addition of water
420 mL). The resulting mixture was extracted with chloro-
form 43£20 mL). The combined organic layers were washed
with water 43£20 mL) and brine 43£5 mL), dried with
anhydrous MgSO4, ®ltered, and concentrated under reduced
pressure. The crude product was puri®ed by ¯ash column
chromatography to give 72.0 mg 489%) of enyne 10 as a
yellowish solid. The analytical sample was recrystallized
from hexane and chloroform to yield pure 10: Rfˆ0.57
4EtOAc:hexaneˆ2:1); mp168 8C 4dec.); IR 4KBr) 3413,
4.7. ..E)-4-Stilbenyl)ethyne .16) from dibromide 6 using
BuLi
To a solution of dibromide 6 4174 mg, 0.476 mmol) in dry
THF 410 mL) at room temperature was added 1.20 mL of
BuLi 41.6 M solution in hexane, 1.92 mmol) under N2
atmosphere. After stirring for 1 h, water 420 mL) was
added and the resulting mixture was extracted with chloro-
form 43£20 mL). The combined organic layers were washed
with water 43£20 mL) and brine 43£5 mL), dried with
anhydrous MgSO4, ®ltered and concentrated under reduced
pressure. The crude product was puri®ed by ¯ash column
chromatography to give 88.0 mg 490%) of alkyne 16 as a
yellowish solid. The analytical sample was recrystallized
from hexane to yield pure 16: Rfˆ0.57 4CHCl3:
hexaneˆ1:2); mp121 8C; IR 4KBr) 3285, 3023, 2105, 970,
824, 691, 548 cm21; 1H NMR d 7.45±7.54 4m, 6H), 7.35±
7.40 4m, 2H), 7.24±7.31 4m, 1H), 7.14 4d, 1H, Jˆ16.4), 7.07
4d, 1H, Jˆ16.4), 3.13 4s, 1H); 13C NMR d 137.7, 136.9,
132.4, 129.8, 128.7, 127.9, 127.7, 126.6, 126.3, 120.9,
83.7, 77.9; MS 4EI) m/z 4%): 204 4M1, 100), 189 418),
101 49); HRMS 4EI) calcd for C16H12 204.0939, found
204.0940.
1
3031, 2927, 1045, 968, 821, 694, 532 cm21; H NMR d
7.46-7.53 4m, 4H), 7.34-7.39 4m, 4H), 7.24-7.29 4m, 1H),
7.13 4d, 1H, Jˆ16.5), 7.07 4d, 1H, Jˆ16.5), 6.91 4d, 1H,
Jˆ16.3), 6.16 4dt, 1H, Jˆ16.3, 2.1), 3.79 4t, 2H, Jˆ6.1),
2.67 4dt, 2H, Jˆ6.1 and 2.1), 1.87 4br, 1H); 13C NMR d
140.5, 137.6, 137.1, 135.6, 129.0, 128.7, 128.0, 127.8,
126.8, 126.6, 126.5, 107.9, 89.1, 81.8, 61.2, 24.1; MS 4EI)
m/z 4%): 274 4M1, 100), 241 416), 228 438); HRMS 4EI)
calcd for C20H18O 274.1358, found 274.1366.
4.5. Pyrrolidine ..E)-4-styrenyl)phenylacetamide .14)
To a solution of dibromide 5 4184 mg, 0.500 mmol),
PdCl24PPh3)2 435.1 mg, 0.0500 mmol) and PPh3 426.1 mg,
0.100 mmol) in pyrrolidine 45 mL) at room temperature was
added 6 478.0 mg, 1.10 mmol) under N2 atmosphere. After
stirring for 20 h, 1 N HCl 420 mL) was added to the reaction
mixture and the resulting mixture was extracted with chloro-
form 43£10 mL). The combined organic layers were washed
with water 43£20 mL) and brine 43£5 mL), dried with
anhydrous MgSO4, ®ltered, and concentrated under reduced
pressure. The crude product was puri®ed by ¯ash column
chromatography to give 100 mg 468%) of acetamide 14 as a
pale yellow solid: Rfˆ0.15 4EtOAc:hexaneˆ2:1); mp147±
1488C; IR 4KBr) 3026, 2966, 1641, 1426, 962, 792, 697,
4.8. 1-Bromo-2-..E)-4-stilbenyl)ethene .17)
To a solution of dibromide 5 4174 mg, 0.476 mmol),
Pd4PPh3)4 428.0 mg, 0.0238 mmol) in DMF 45 mL) at
room temperature were added diisopropylethylamine
40.124 mL, 0.720 mmol) and Bu3SnH 4146 mg,
0.500 mmol) under N2 atmosphere. After 1 h of stirring,
water 420 mL) was added and the resulting mixture was
extracted with chloroform 43£20 mL). The combined
organic layers were washed with water 43£20 mL) and
brine 43£5 mL), dried with anhydrous MgSO4, ®ltered,
and concentrated under reduced pressure. The crude product
was puri®ed by ¯ash column chromatography to give
1
534 cm21; H NMR d 7.46±7.53 4m, 4H), 7.23±7.38 4m,
5H), 7.09 4s, 2H), 3.66 4s, 2H), 3.50 4t, 2H, Jˆ6.8), 3.43 4t,
2H, Jˆ6.7), 1.80±1.97 4m, 4H); 13C NMR d 169.3, 137.3,
135.8, 134.3, 129.2, 128.6, 128.4, 128.2, 127.5, 126.6,
126.4, 46.8, 45.9, 42.0, 26.1, 24.3; MS 4EI) m/z 4%): 291
4M1, 79), 193 426), 98 4100); HRMS 4EI) calcd for
C20H21ON 291.1623, found 291.1615.
121 mg 490%) of
a
stereoisomeric mixture, 17
44Z):4E)ˆ,13:1), as a yellowish solid. The 4Z)-isomer of
17: Rfˆ0.57 4CHCl3:hexaneˆ1:2); IR 4KBr) 3022, 2922,
1
965, 828, 688, 538 cm21; H NMR d 7.72 4d, 2H, Jˆ8.4),
4.6. 1-Bromo-2-..E)-4-stilbenyl)ethyne .15)
7.51±7.54 4m, 4H), 7.26±7.40 4m, 3H), 7.17 4d, 1H,
Jˆ16.4), 7.10 4d, 1H, Jˆ16.4), 7. 07 4d, 1H, Jˆ8.1), 6.43
4d, 1H, Jˆ8.1); 13C NMR d 137.3, 137.2, 134.1, 131.9,
129.4, 129.3, 128.7, 128.1, 127.8, 126.5, 126.3, 106.2; MS
To a solution of dibromide 5 4110 mg, 0.300 mmol) in dry
THF 45 mL) at 2788C was added 0.36 mL of NaHMDS

8290
H. B. Lee et al. / Tetrahedron 57 &2001) 8283±8290
4EI) m/z 4%) 286 4M112, 99), 284 4M1, 100), 203 460), 101
431).
Catalysts, John Wiley & Sons: Chichester, 1995; pp.
168±188. 4c) Diederich, F.; Stang, P. J. In Metal-catalyzed
Cross-coupling Reactions, Wiley-VCH: Weinheim, 1998;
pp. 213±219.
4.9. 1,4-Bis..E)-4-stilbenyl)buta-1,3-diyne .18)
4. Very recently, the formation of the 1,3-diynes from the
1,1-dibromo-1-alkenes was reported: Shen, W.; Thomas,
S. A. Org. Lett. 2000, 2, 2857±2860.
To a solution of alkynyl bromide 15 470.0 mg, 0.247 mmol),
PdCl24PPh3)2 417.4 mg, 0.025 mmol), TFP 411.5 mg,
0.049 mmol), and CuI 49.4 mg, 0.049 mmol) in benzene
43 mL) at room temperature were added TEA 4100.1 mg,
0.989 mmol) and alkyne 16 450.5 mg, 0.247 mmol) under
N2 atmosphere. After 2 h of stirring, the product was
obtained as a ¯oating solid. A solution of saturated aq.
NH4Cl 410 mL) was added to the reaction mixture and
the resulting mixture was extracted with chloroform
43£10 mL). The residue was washed with chloroform
43£20 mL). The crude product was recrystallized from
benzene 4150 mL) to give 40.0 mg 440%) of homodiyne
18 as yellowish needles: Rfˆ0.31 4EtOAc:hexaneˆ1:2);
mp274-275 8C; IR 4KBr) 3022, 2141, 1494, 1446, 1408,
5. Formation of the symmetric 1,3-diynes from the 1,1-dibromo-
1-alkenes: 4a) Galamb, V.; Gopal, M.; Alper, H. Organo-
metallics 1983, 2, 801±805. 4b) Soderquist, J. A.; Leon, G.;
Colberg, J. C.; Martinez, I. Tetrahedron Lett. 1995, 36, 3119±
3122.
6. While our work was in progress, the ®rst systematic study on
the formation of the conjugated enynes from the Stille
reactions of the 1,1-dibromo-1-alkenes was reported:
4a) Shen, W.; Wang, L. J. J. Org. Chem. 1999, 64, 8873±
8879. See also: 4b) Zapata, A. J.; Ruiz, J. J. Organomet.
Chem. 1994, 479, C6±C8.
7. Ramirez, F.; Desai, N. B.; McKelvie, N. J. Am. Chem. Soc.
1962, 84, 1745±1747.
1
970, 821, 754, 669, 542 cm21; H NMR d 7.45±7.52 4m,
8. 4a) Seebach, D.; Neumann, H. Tetrahedron Lett. 1976, 4839±
4842. 4b) Miller, R. B.; McGarvey, G. J. Org. Chem. 1979, 44,
4623±4633.
6H), 7.33±7.38 4m, 2H), 7.25±7.29 4m, 1H), 7.15 4d, 1H,
Jˆ16.3), 7.10 4d, 1H, Jˆ16.3); 13C NMR d 137.1, 132.9,
130.5, 128.8, 128.1, 128.0, 127.9, 126.5, 120.9, 100.7, 77.2;
MS 4EI) m/z 4%) 406 4M1, 100), 114 434); HRMS 4EI) calcd
for C32H22 406.1722, found 406.1729.
9. 4a) Alami, M.; Linstrumelle, G. Tetrahedron Lett. 1991, 32,
6109±6112. 4b) Alami, M.; Ferri, F.; Linstrumelle, G.
Tetrahedron Lett. 1993, 34, 6403±6406.
10. Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585±
9595.
Acknowledgements
11. 4a) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769±
3772. 4b) Uenishi, J.; Kawahama, R.; Tanio, A.; Wakabayashi,
S.; Yonemitsu, O. Tetrahedron 1997, 53, 2439±2448.
12. 4a) Uenishi, J.; Kawahama, R.; Shiga, Y.; Yonemitsu, O.;
Tsuji, J. Tetrahedron Lett. 1996, 37, 6759±6762. 4b) Uenishi,
J.; Kawahama, R.; Yonemitsu, O.; Tsuji, J. J. Org. Chem.
1998, 63, 8965±8975.
This work was supported in part by the Brain Korea 21
Project and in part by a grant No. KOSEF 97-0502-0901-5
from the Korea Science and Engineering Foundation.
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