Unusual regioselectivity of Pd(0)-catalyzed coupling reaction of electron-deficient alkenyl halides with allenic/propargylic zinc reagents. Highly selective synthesis of 6-phenylhex-5-yn-2(or 3)-enoates/enitrile and 4-phenyl-6-substituted-hexa-2,4,5-trienoates

Article abstract of DOI:10.1021/jo991243g

The Pd(0)-catalyzed coupling reaction of electron-deficient alkenyl halides with the organozinc formed by the subsequent treatment of 1- phenylalk-1-yne with n-BuLi and ZnBr₂ with or without a catalytic amount of HgCl₂ was studied. Both the allene-formation- and the alkyne-formation-type coupling reactions were observed with high regio- and stereoselectivity: the reaction of 1-phenylprop-1-yne afforded 6-phenylhex-5-yn-2(or 3)-enoates and -enitriles, while the reaction of 1-phenylhex-1-yne formed 4-phenyl-6- substituted-hexa-2,4,5-trienoates. A plausible explanation for the regioselectivity was discussed. The double bonds in 6-phenylhex-5-yn-2- enoates were prone to migrate to the position conjugated with the carbon- carbon triple bonds to form 6-phenylhex-5-yn-3-enoates at higher temperature. The migration did not occur in absence of an excess amount of allenic/propargylic zinc reagent or at low temperature.

Full text of DOI:10.1021/jo991243g

J . Org. Chem. 2000, 65, 2287-2291
2287
Un u su a l Regioselectivity of P d (0)-Ca ta lyzed Cou p lin g Rea ction of
Electr on -Deficien t Alk en yl Ha lid es w ith Allen ic/P r op a r gylic Zin c
Rea gen ts. High ly Selective Syn th esis of 6-P h en ylh ex-5-yn -2(or
3)-en oa tes/En itr ile a n d
4-P h en yl-6-su bstitu ted -h exa -2,4,5-tr ien oa tes
Shengming Ma,*,† Aibin Zhang,† Yihua Yu,‡ and Wei Xia‡
Laboratory of Organometallic Chemistry and Department of Analytical Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received August 5, 1999
The Pd(0)-catalyzed coupling reaction of electron-deficient alkenyl halides with the organozinc
formed by the subsequent treatment of 1-phenylalk-1-yne with n-BuLi and ZnBr2 with or without
a catalytic amount of HgCl2 was studied. Both the allene-formation- and the alkyne-formation-
type coupling reactions were observed with high regio- and stereoselectivity: the reaction of
1-phenylprop-1-yne afforded 6-phenylhex-5-yn-2(or 3)-enoates and -enitriles, while the reaction of
1-phenylhex-1-yne formed 4-phenyl-6-substituted-hexa-2,4,5-trienoates. A plausible explanation for
the regioselectivity was discussed. The double bonds in 6-phenylhex-5-yn-2-enoates were prone to
migrate to the position conjugated with the carbon-carbon triple bonds to form 6-phenylhex-5-
yn-3-enoates at higher temperature. The migration did not occur in absence of an excess amount
of allenic/propargylic zinc reagent or at low temperature.
Sch em e 1
In tr od u ction
Formation of C-C bonds is one of the major objectives
in organic synthesis. Cross-coupling reaction between an
organometallic reagent and R′X (R′) alkenyl, aryl) with
a transition-metal catalyst is very attractive because of
the easy availability of both reactants.1 For the coupling
reaction between an organic halide and an allenic/
propargylic metallic reagent there are, in principle, two
outcomes: (1) the formation of allenes (pathway I) and
(2) the formation of alkynes (pathway II) (Scheme 1).
Recently, we developed the HgCl2-catalyzed mono-
lithiation reaction of 1-arylalk-1-ynes. A catalytic amount
of HgCl2 was found to be crucial to avoid the polylithia-
tion reaction.2 The subsequent reaction of the lithium
reagent formed in situ with benzylic3 and allylic4 halides
was studied. Moreover, on the basis of this monolithiation
reaction, a Pd(0)-catalyzed coupling reaction of aromatic
halides with allenic/propargylic zinc reagents, which were
formed in situ via transmetalation reaction, was devel-
oped for the efficient and selective synthesis of 1,1-diaryl-
1,2-dienes (pathway I, Scheme 1).5 It is interesting to
observe that ZnBr2 has similar effect on the monometa-
lation reaction of 1-arylalk-1-ynes. In this paper, we
disclose our most recent results on the coupling reaction
of the organozinc reagents with alkenyl halides, which
show both pathway I- and pathway II-type regiochem-
istry with high selectivity, depending on the structure
of organic halides and 1-arylalk-1-ynes.
Resu lts a n d Discu ssion
As is reported in ref 5, the treatment of 1-phenylprop-
1-yne with n-BuLi in the presence of 1.5 mol % HgCl2 in
THF at -78 °C followed by the addition of 1.5 molar equiv
of ZnBr2 (defined as procedure A), (E)-1-iodohexene, and
5 mol % Pd(PPh3)4 did not afford any coupling product.
Neither did (E)-1-iodostyrene. However, when R-bro-
mostyrene was used, it afforded 2,3-diphenyl-1,3,4-triene
3a in 29% yield. Presumably, R-bromostyrene was not
active enough, so R-iodostyrene was used, but the yield
of the coupling product 3a was only increased to 33%
(Scheme 2). Here, it is important to note that the coupling
reaction afforded the pathway-I type allenic triene prod-
uct 3a , not 2,5-diphenylalk-4-yn-1-ene 3b, which is
consistent with the results of aromatic halides.
From the above experiment, it is obvious that the sub-
stituent as well as its location in alkenyl halides affected
the reaction greatly. To our surprise, the corresponding
reaction of ethyl (Z)-3-iodopropenoate afforded a pathway-
II type product, i.e., ethyl 6-phenylhex-5-yn-2(Z)-enoate
((Z)-4a ), exclusively. A similar result was obtained with
ethyl (Z)-3-bromopropenoate, but no reaction was ob-
served with ethyl (Z)-3-chloropropenoate (Scheme 3). The
configuration of the CdC bond remained intact.
† Laboratory of Organometallic Chemistry.
‡ Department of Analytical Chemistry.
(1) Trost, B. M., Fleming, I., Eds. Comprehensive Organic Synthesis;
Pergaman Press: Oxford, 1991; Vol. 3.
(2) (a) De J ong, R. L. P.; Brandsma, L. J . J . Organomet. Chem. 1986,
312, 277. (b) De J ong, R. L. P.; Brandsma, L. J . Ibid. 1982, 238, C17.
(c) Becker, J . Y.; Klein, J . J . Organomet. Chem. 1978, 157, 1. (d) Becker,
J . Y. J . Organomet. Chem. 1976, 118, 247.
(3) Ma, S.; Wang, L. J . Org. Chem. 1998, 63, 3497.
(4) Ma, S.; Wang, L. Chin. J . Chem. 1999, 17, 531.
(5) Ma, S.; Zhang, A. J . Org. Chem. 1998, 63, 9601.
10.1021/jo991243g CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/25/2000

2288 J . Org. Chem., Vol. 65, No. 8, 2000
Ma et al.
Sch em e 2
Sch em e 4a
Sch em e 3
When its steric isomer, i.e., ethyl (E)-3-iodopropenoate,
was used, the coupling reaction at -5 °C afforded
(E)-4a as the sole product in 88% yield (Scheme 4).
However, the corresponding reaction under conditions A
afforded three products, ethyl 6-phenylhex-5-yn-3(Z)-
enoate ((Z)-5a ), ethyl 6-phenylhex-5-yn-3(E)-enoate
((E)-5a ), and ethyl 6-phenylhex-5-yn-2(E)-enoate ((E)-4a ),
in a ratio of 35:21:44 in 58% combined yield at 20 °C.
Ratios depend on the temperature for the coupling
reaction (Scheme 4).
The structures of (Z)-4a , (E)-4a , (Z)-5a , and (E)-5a
were determined by HMBC (heteronuclear multiple-bond
connectivity) spectra of (Z)-4a and (Z)-5a . The configu-
ration of the carbon-carbon double bond was determined
by the coupling constants of the olefinic protons.
To further confirm the structures of these products,
p-nitrobenzyl (E)-3-iodopropenoate was prepared, and the
corresponding reaction with or without HgCl2 afforded
three corresponding products 4c, (Z)-5b, and (E)-5b
(Scheme 4).
By recrystallization, pure p-nitrobenzyl 6-phenylhex-
5-yn-3(E)-enoate (E)-5b was obtained in the form of single
crystals. Thus, its structure was further confirmed by
X-ray single-crystal diffraction study (see the Supporting
Information for the ORTEP presentation). Moreover, the
migration of the carbon-carbon double bond in (Z)-4a
could also be furnished to afford (Z)-5a and (E)-5a in
DMF at 50 °C completely (Scheme 4). Thus, it is obvious
that 5a was formed via the migration of carbon-carbon
double bond in 4a .
When (E)-4a was subsequently treated with 1.5 mol
% HgCl2 and 5 mol % Pd(PPh3)4, the CdC bond migra-
tion reaction was not observed, ruling out the possi-
bility of HgCl2- and/or Pd(PPh3)4-catalyzed migration of
the CdC bond in (E)-4a . However, in the presence of
an excess amount of the in-situ generated allenic/prop-
argynic zinc reagents, (E)-4a isomerized to a mixture of
(E)-4a , (Z)-5a , and (E)-5a at 21 °C. The CdC bond
migration reaction at -15 f -10 °C did not occur. Thus,
the excess amount of the zinc reagent and the temper-
a
Expressed in terms of the amount of 3-phenylprop-1-yne
added.
ature of the coupling reaction are responsible for the
migration of the CdC double bond in 4a -type products
(Scheme 4).
(Z)-3-Iodopropenitrile could react similarly with the
organozinc reagent formed by the subsequent treatment
of 1-phenylprop-1-yne with n-BuLi and ZnBr2 in the
presence of HgCl2 under the catalysis of Pd(PPh3)4 to
afford 6-phenylhex-5-yn-2(Z)- enitrile (4f). While methyl
R-bromopropenoate was used instead of ethyl (Z)-3-
iodopropenoate, the reaction was complicated. Some
representative examples with or without HgCl2 are
summarized in Table 1; in most cases the results with
HgCl2 are somewhat better.
On the other hand, it is interesting to observe that, by
starting from 1-phenylhex-1-yne, both ethyl (Z)-3-io-
dopropenoate and ethyl (E)-3-iodopropenoate afforded the
allenic product ethyl 4-phenylnona-2(E),4,5-trieneoate
(E)-7a in 73% and 86% yields, respectively (Table 2).
The configuration of carbon-carbon double bond in 7a
was determined to be E since the coupling constant of
the olefinic protons is 15.8 Hz. In contrast, when methyl
(Z)-3-iodobutenoate was used, the configuration of the
carbon-carbon double bond in product 7d was confirmed
to be Z by the 2D H-1H NOESY experiment of (Z)-7d
(Figure 1). Thus, it is believed that in this case the
configuration of the C-C double bond is retained during
1

Coupling Reaction of Electron-Deficient Alkenyl Halides
J . Org. Chem., Vol. 65, No. 8, 2000 2289
Ta ble 1. P d (0)-Ca ta lyzed Cou p lin g Rea ction of
Electr on -Deficien t Alk en yl Ha lid es w ith th e Or ga n ozin c
Rea gen ts F or m ed by th e Su bsequ en t Tr ea tm en t of
1-P h en ylp r op -1-yn e w ith n -Bu Li a n d Zn Br 2 w ith or
w ith ou t th e Ad d ition of HgCl2
Sch em e 5
We did some further experiments to probe the mech-
anism of this reaction. In the absence of Pd(PPh3)4, the
reaction of ethyl (Z)-3-iodopropenoate with the organozinc
formed in situ by the subsequent treatment of 1-phenyl-
prop-1-yne with n-BuLi and ZnBr2 did not occur, ruling
out the possibility of uncatalyzed Michael addition of the
organozinc reagent to the conjugated CdC bond6 followed
by elimination of X- to afford the alkynic products.
While the mixture of phenyl iodide (0.5 mmol) and
ethyl (Z)-3-iodopropenoate (0.5 mmol) reacted with the
organozinc reagent formed by the treatment of 1-phen-
ylprop-1-yne (0.85 mmol) with n-BuLi (0.94 mmol) and
ZnBr2 under the catalysis of Pd(PPh3)4 (29 mg, 0.025
mmol), it afforded a mixture of 1,1-diphenylpropa-1,2-
diene and (Z)-4a in a ratio of 4:1, indicating that the
coupling reaction of phenyl iodide is much faster than
that of ethyl (Z)-3-iodopropenoate (Scheme 5).
entry
2
T (oC)
time (h)
product
yielda (%)
1
2a
2a
2a
2b
2b
2e
2e
2f
0
0
0
1
(Z)-4a
(Z)-4a
(Z)-4a
(Z)-4b
(Z)-4b
(Z)-4e
(Z)-4e
(Z)-4f
(Z)-4f
60
66
62
62
54
49
39
90
87
2b
3c
4
1.5
2.5
1
1.5
2.5
0.5
1.2
1
-3 f 0
-3 f 0
50
50
-15 f 0
-15 f 0
5b
6
7b
8
9b
2f
It has been reported that in most cases the oxidative
addition reaction of Pd(0) with allenic bromides or
propargylic halides afforded completely or predominantly
η1-allenyl palladium species.7 However, the equilibrium
between η1-allenyl palladium, η1-propargyl palladium,
and η3-propargyl palladium complexes depends on the
ligands8 used as well as the substituents at the propargyl
moiety;9,10 thus, a unified mechanism (Scheme 6) was
proposed for this reaction. With 3-phenylprop-1-yne (R
) H), the 6-phenylhex-5-yn-2-enoates 4 were formed via
the reductive elimination of η1-propargyl-type of pal-
ladium intermediate 10,11 while with 3-phenylhex-1-yne,
probably due to the steric hindrance of R, 2,4,5-trienoates
7 were formed exclusively via the reductive elimination
of η1-allenyl-type of palladium intermediate 9.12 The
different regioselectivity observed here may be derived
from the competing reactivity of either two isomeric
organozincs or two isomeric palladium species.
a
b
Isolated yield. In absence of HgCl2. c 5 mol % PdCl2(PPh3)2
was used as the catalyst.
Ta ble 2. P d (0)-Ca ta lyzed Cou p lin g Rea ction of
Electr on -Deficien t Alk en yl Ha lid es w ith th e Or ga n ozin c
Rea gen ts F or m ed by th e Su bsequ en t Tr ea tm en t of
1-P h en ylh ex-1-yn e w ith n -Bu Li a n d Zn Br 2 w ith or
w ith ou t th e Ad d ition of HgCl2
entry
2a
time (h)
product
yieldb (%)
(6) (a) Kawakami, Y.; Tsuruta T. Tetrahedron Lett. 1971, 1173. (b)
Kawakami, Y.; Tsuruta T. Tetrahedron Lett. 1971, 1959. (c) Tsuruta
T.; Kawakami, Y. Tetrahedron 1973, 29, 1173. (d) Malzieu, R. Bull.
Soc. Chim. Fr. 1966, 2682. (e) Daviaud, G.; Miginiac P. Bull. Soc. Soc.
Fr. 1970, 1617. Moreau, J .-L.; Frangin, Y.; Gaudemar, M. Bull. Soc.
Chim. Fr. 1970, 4511. (f) Daviaud, G.; Massy M.; Miginiac, P. Tetra-
hedron Lett. 1970, 5169. (g) Daviaud, G.; Massy-Bardot, M.; Miginiac,
P. C. R. Hebd. Seances Acad. Sci., Ser. C 1971, 272, 969. (h) Gaudemar-
Bardone, F.; Mladenova, M.; Gaudemar, M. Synthesis 1988, 611. (i)
Frangin, Y.; Guimbal, G.; Wissocq, F.; Zamarlik, H. Synthesis 1986,
1046. (j) Barbot, F.; Paraiso, E.; Miginiac, P. Tetrahedron Lett. 1984,
25, 4369.
(7) (a) J effery-Luong, T.; Linstrumelle, G.Tetrahedron Lett. 1980,
21, 5019. (b) Tsuji J .; Watanabe H.; Minami I.; Shimizu I. J . Am. Chem.
Soc. 1985, 107, 2196. (c) For the synthesis of pure η1-allenyl palladium
complexes from the oxidative addition reaction of Pd(0) with allenylic
bromides, see: Wouters, J . M. A.; Klein, R. A.; Elsevier: C. J .; Ha¨ming,
L.; Stam, C. H. Organometallics 1994, 13, 4586. (d) For the synthesis
of η1-allenyl palladium complexes from the oxidative additon reaction
of Pd(0) with propargyl halides, see: Elsevier: C. J .; Kleijn, H.; Ruiten-
berg, K.; Vermeer, P. J . Chem. Soc., Chem. Commun. 1983, 1529.
(8) Tsutsumi, K.; Ogoshi, S.; Nishiguchi, S.; Kurosawa, H. J . Am.
Chem. Soc. 1998, 120, 1938.
1
2a
2a
2b
2b
2c
2c
2d
2e
2e
2.25
2.5
2
3
2.5
2
2.5
23
18
(E)-7a
(E)-7a
(E)-7b
(E)-7b
(E)-7a
(E)-7a
(Z)-7d
(Z)-7e
(Z)-7e
73
30
85
58
86
78
77
47
40
2c
3
4c
5
6c
7
8d
9c,d
a
b
See Table 1 for the structures of 2a ,b and 2d ,e. Isolated
yield. c In absence of HgCl2. 50% of 2e was recovered.
d
F igu r e 1.
(9) Ogoshi, S.; Tsutsumi, K.; Kurosawa, H. J . Organomet. Chem.
1995, 493, C19.
the reaction. Some representative examples with or
without the addition of HgCl2 are summarized in Table
2; here again, the yields in the presence of HgCl2 are
usually higher.5
(10) Elsevier, C. J .; Kleijn, H.; Boersma, J .; Vermeer, P. Organo-
metallics 1986, 5, 716.
(11) It should be noted that under procedure A 1-phenylprop-1-yne
afforded a mixture of allenic and propargylic zinc reagents; see ref 5.
(12) Russel, C. E.; Hegedus, L. S. J . Am. Chem. Soc. 1983, 105, 943.

2290 J . Org. Chem., Vol. 65, No. 8, 2000
Ma et al.
at rt. After the reaction was complete, as monitored by TLC
(eluent: petroleum ether), it was quenched with water and
extracted with petroleum ether. Drying over MgSO4, rotary
evaporation, and chromatography on silica gel (eluent: petrol-
uem ether) afforded 36 mg (33%) of 2,3-diphenylpenta-1,3,4-
triene (3a ): 1H NMR 7.55-7.05 (m, 10H), 5.70 (s, 1H), 5.40
(s, 1H), 5.15 (s, 2H); MS m/e 218 (M+, 100); IR (neat) 1938,
1600 cm-1; HRMS calcd for C17H14 218.1092, found 218.1100.
Eth yl 6-p h en ylh ex-5-yn -2(Z)-en oa te ((Z)-4a ) was pre-
pared similarly, starting from 1 (99 mg, 0.85 mmol) and 2a
(113 mg, 0.5 mmol) to afford 71 mg (66%) of (Z)-4a : 1H NMR
7.40-7.20 (m, 5H), 6.28 (dt, J ) 11.3, 6.7 Hz, 1H), 5.80 (dt, J
) 11.3, 1.9 Hz, 1H), 4.15 (q, J ) 7.1 Hz, 2H), 3.80 (dd, J ) 6.7,
1.9 Hz, 2H), 1.30 (t, J ) 7.1 Hz, 3H); MS m/e 214 (M+, 46.13),
141 (100); IR (neat) 2200, 1720, 1645, 1600, 1200 cm-1. Anal.
Calcd for C14H14O2: C, 78.48; H, 6.59. Found: C, 78.50; H,
6.71.
Sch em e 6
Meth yl 6-p h en ylh ex-5-yn -2(Z)-en oa te ((Z)-4b) was pre-
pared similarly, starting from 1 (99 mg, 0.85 mmol) and 2b
(106 mg, 0.5 mmol) to afford 62 mg (62%) of (Z)-4b: 1H NMR
7.45-7.20 (m, 5H), 6.38 (dt, J ) 11.3, 6.8 Hz, 1H), 5.90 (dt, J
) 11.3, 2.1 Hz, 1H), 3.85 (dd, J ) 6.8, 2.1 Hz, 2H), 3.75 (s,
3H); MS m/e 200 (M+, 68.21), 115 (100); IR (neat) 2240, 1730,
1655, 1600, 1220, 1180 cm-1; HRMS calcd for C13H12O2
200.0834, found 200.0847.
In conclusion, we have observed two different types of
coupling patterns for the Pd(0)-catalyzed reaction of
allenic/propargylic zinc reagents with organic halides; the
regioselectivity of the coupling reaction depends not only
on the structure of organic halides, but also on that of
1-arylalk-1-ynes. The tendency for the migration of
CdC double bond in products 4a depends largely on the
excess amount of zinc reagent and the reaction temper-
ature. Although the rational has been discussed, the real
effect on the regioselectivity still needs further attention.
In most cases, the configurations of the CdC bonds in
the alkenyl halides remained intact. By the methodology
described in this paper, 6-phenylhex-5-yn-2-enoates/
enitriles and 4-phenyl-6-substitutedhexa-2,4,5-trienoates
can be prepared highly regio- and stereoselectively.
Meth yl 3,6-d ip h en ylh ex-5-yn -2(Z)-en oa te ((Z)-4e) was
prepared similarly, starting from 1 (99 mg, 0.85 mmol) and
2e (144 mg, 0.5 mmol) to afford 67 mg (49%) of (Z)-4e: 1H
NMR 7.65-7.55 (m, 2H), 7.45-7.35 (m, 3H), 7.25-7.15 (m,
5H), 6.20 (s, 1H), 4.32 (s,2H), 3.80 (s, 3H); MS m/e 276 (M+,
57.01), 215 (100); IR (neat) 2200, 1720, 1630, 1600, 1190, 1170
cm-1; HRMS calcd for C19H16O2: 276.1146, found 276.1139.
P d (P P h 3)4-Ca ta lyzed Cou p lin g Rea ction of Eth yl (E)-
3-Iod op r op en oa te w ith Or ga n ozin c F or m ed by th e Su b-
sequ en t Rea ction of 1-P h en ylp r op -1-yn e w ith n -Bu Li
a n d Zn Br 2 in th e P r esen ce of HgCl2. Starting from 1 (99
mg, 0.85 mmol) and 2c (113 mg, 0.5 mmol) to afford 27 mg
(25%) of (E)-4a , 22 mg (21%) of (Z)-5a , and 13 mg (12%) of
(E)-5a . Eth yl 6-p h en ylh ex-5-yn -3(Z)-en oa te ((Z)-5a ): 1H
NMR 7.45-7.15 (m, 5H), 6.15 (dt, J ) 10.9, 7.1 Hz, 1H), 5.85
(dt, J ) 10.9, 1.1 Hz, 1H), 4.15 (q, J ) 7.1 Hz, 2H), 3.45 (dd,
J ) 7.1, 1.1 Hz, 2H), 1.25 (t, J ) 7.1 Hz, 3H); MS m/e 214
(M+, 43.45), 141 (100); IR (neat) 2190, 1731, 1661, 1595, 1180
cm-1; HRMS calcd for C14H14O2 214.0990, found 214.0995.
Eth yl 6-p h en ylh ex-5-yn -3(E)-en oa te ((E)-5a ): 1H NMR
7.45-7.20(m, 5H), 6.30 (dt, J ) 15.8, 7.3 Hz, 1H0, 5.84 (dt, J
) 15.8, 1.6 Hz, 1H), 4.17 (q, J ) 7.2, 2H), 3.20 (dd, J ) 7.3,
1.6 Hz, 2H), 1.25 (t, J ) 7.2 Hz, 3H); MS m/e 214 (M+, 43.45),
141 (100); IR (neat) 1731, 1595, 1257, 1164 cm-1; HRMS calcd
for C14H14O2 214.0990, found 214.0988.
P d(P P h 3)4-Catalyzed Cou plin g Reaction of p-Nitr oben -
zyl (E)-3-Iod op r op en oa te w ith Or ga n ozin c F or m ed by
t h e R ea ct ion of 1-P h en ylp r op -1-yn e w it h n -Bu Li a n d
Zn Br 2 in th e P r esen ce of HgCl2. Starting from 1 (99 mg,
0.85 mmol) and p-nitrobenzyl (E)-3-iodopropenoate (167 mg,
0.5 mmol) to afford 4c, (Z)-5b, and (E)-5b in an NMR ratio of
0.54:2:1 in 80% combined yield. Recrystallization with the
mixture of petroleum ether and ethyl acetate afforded the
single crystals of (E)-5b. p-Nitr oben zyl 6-p h en ylh ex-5-yn -
3(E)-en oa te ((E)-5b): 1H NMR 8.23 (d, J ) 8.8 Hz, 2H), 7.52
(d, J ) 8.8 Hz, 2H), 7.48-7.35 (m, 2H), 7.35-7.25 (m, 3H),
6.28 (dt, J ) 15.8, 7.2 Hz, 1H), 5.82 (dt, J ) 15.8, 1.3 Hz, 1H),
5.20 (s, 2H), 3.30 (dd, J ) 7.2, 1.3 Hz, 2H); MS m/e 321 (M+,
48.17), 141 (100); IR (neat) 1735, 1605, 1190, 1160 cm-1. Anal.
Calcd for C19H15NO4: C, 71.02; H, 4.71; N, 4.36. Found: C,
70.90; H, 4.70; N, 4.52.
Exp er im en ta l Section
Ma ter ia ls. n-BuLi (solution in hexane), (E)-1-iodostyrene,13
(E)-1-iodohexene,13 methyl (Z)-3-iodopropenoate,14 ethyl (Z)-
3-iodopropenoate,14 ethyl (Z)-3-bromopropenoate,14 ethyl (Z)-
3-chloropropenoate,14 methyl (Z)-3-iodobutenoate,14 methyl (Z)-
3-phenyl-3-iodopropenoate,14 and (Z)-3-iodopropenitrile14 were
prepared according to the literature methods. R-Bromostyrene
and R-iodostyrene were commercially available and used after
they were dried via the azeotropic evaporation with benzene.
1H NMR spectra (δ) were measured using CDCl3 as the solvent
and Me4Si as the internal standard, unless otherwise stated.
Ethyl (E)-3-iodopropenoate (2c), ethyl (E)-3-bromoprope-
noate, and 4-nitrobenzyl (E)-3-iodopropenoate were prepared
via the reaction of (E)-3-halopropenoic acid,15 K2CO3, and the
corresponding organic halides in DMF.
P d (P P h 3)4-Ca ta lyzed Cou p lin g Rea ction of R-Iod osty-
r en e with Or gan ozin c For m ed by th e Reaction of 1-P h en -
ylp r op -1-yn e w ith n -Bu Li a n d Zn Br 2 in th e P r esen ce of
HgCl2. To a solution of HgCl2 (2 mg, 0.007 mmol, 1.5 mol %)
and 1-phenylprop-1-yne (58 mg, 0.5 mmol) in THF (2 mL) in
a dry Schlenk tube was added n-BuLi (0.35 mL, 1.6 M in
hexane, 0.55 mmol) at -78 °C under N2. After 100 min at -78
°C, dry ZnBr2 (169 mg, 0.75 mmol) in THF (3 mL) was added.
After 10 min at this temperature, the reaction mixture was
warmed to room temperature and stayed at rt for 20 min, and
a solution of Pd(PPh3)4 (29 mg, 0.025 mmol) and R-iodostyrene
(112 mg, 0.5 mmol) in THF (1 mL) was added subsequently
The detailed information for the X-ray structure determi-
nation of (E)-5b was included in the Supporting Information.
P d (P P h 3)4-Ca ta lyzed Cou p lin g Rea ction of Eth yl (E)-
3-Iod op r op en oa te w ith Or ga n ozin c F or m ed by th e Su b-
sequ en t Rea ction of 1-P h en ylp r op -1-yn e w ith n -Bu Li
a n d Zn Br 2 in Absen ce of HgCl2. To a solution of 1-phenyl-
prop-1-yne (99 mg, 0.85 mmol) in THF (2 mL) in a dry Schlenk
tube was added n-BuLi (0.7 mL, 1.6 M in hexane, 0.94 mmol)
at -78 °C under N2. After 100 min at -78 °C, dry ZnBr2 (278
(13) Stille, J . K.; Simpson, J ames H. J . Am. Chem. Soc. 1987, 109,
2138.
(14) Ma, S.; Lu, X.; Li, Z. J . Org. Chem. 1992, 57, 709. For a review,
see: Ma, S.; Lu, X. Chin. J . Chem. 1998, 16, 388.
(15) Ma, S.; Lu, X. J . Chem. Soc., Chem. Commun. 1990, 1643.

Coupling Reaction of Electron-Deficient Alkenyl Halides
J . Org. Chem., Vol. 65, No. 8, 2000 2291
mg, 1.275 mmol) in THF (3 mL) was added. After 10 min at
this temperature, the reaction mixture was warmed to room
temperature and stayed at room temperature for 20 min, and
a solution of Pd(PPh3)4 (29 mg, 0.025 mmol) and ethyl (E)-3-
iodopropenoate (113 mg, 0.5 mmol) in THF(1 mL) was added
at 0 °C. After the reaction was complete, as monitored by TLC
(eluent: petroleum ether/ethyl acetate ) 100:1), it was quenched
with water and extracted with ether. Drying over MgSO4,
rotary evaporation, and chromatography on silica gel (eluent:
petroluem ether/ethyl acetate ) 100:1) afforded 82 mg (76%)
of ethyl 6-phenylhex-5-yn-2(E)-enoate ((E)-4a ): 1H NMR 7.45-
7.20 (m, 5H), 6.90(dt, J ) 15.5, 5.0 Hz, 1H), 6.15(dt, J ) 15.5,
1.9 Hz, 1H), 4.15(q, J ) 7.2 Hz, 2H), 3.28(dd, J ) 5.0, 1.9 Hz,
2H), 1.20(t, J ) 7.2 Hz, 3H); MS m/e 214 (M+, 36.06), 141 (100);
IR (neat) 2200, 1720, 1660, 1600, 1270, 1170 cm-1. Anal. Calcd
for C14H14O2: C, 78.48; H, 6.59. Found: C, 78.40; H, 6.55.
P d (P P h 3)4-Ca ta lyzed Cou p lin g Rea ction of (Z)-3-Io-
d op r op en itr ile w ith Or ga n ozin c F or m ed by th e Rea c-
tion of 1-P h en ylp r op -1-yn e w ith n -Bu Li a n d Zn Br 2 in th e
P r esen ce of HgCl2. To a solution of HgCl2 (3 mg, 0.011 mmol,
1.5 mol %) and 1-phenylprop-1-yne (99 mg, 0.85 mmol) in THF
(2 mL) in a dry Schlenk tube was added n-BuLi (0.7 mL, 1.6
M in hexane, 0.94 mmol) at -78 °C under N2. After 100 min
at -78 °C, dry ZnBr2 (278 mg, 1.275 mmol) in THF (3 mL)
was added. After 10 min at this temperature, the reaction
mixture was warmed to room temperature and stayed at rt
for 20 min, and then Pd(PPh3)4 (29 mg, 0.025 mmol) and (Z)-
3-iodopropenitrile (90 mg, 0.5 mmol) in THF (1 mL) were
added at -15 °C. After the reaction was complete, as monitored
by TLC (eluent: petroleum ether/ethyl acetate ) 100:1), it was
quenched with water and extracted with ether. Drying over
MgSO4, evaporation, and chromatography on silica gel (elu-
ent: petroluem ether/ethyl acetate ) 100:1) afforded 76 mg
(90%) of 6-phenylhex-5-yn-2(Z)-enitrile ((Z)-4f): 1H NMR
7.45-7.25 (m, 5H), 6.55 (dt, J ) 10.8, 7.1 Hz, 1H), 5.55 (dt, J
) 10.8, 1.6 Hz, 1H), 3.55 (dd, J ) 7.1, 1.6 Hz, 2H); MS m/e
167 (M+, 100); IR (neat) 2221, 1621, 1597, 1569, 1489, 1300
cm-1; HRMS calcd for C12H9N 167.0733, found 167.0720.
P d (P P h 3)4-Ca ta lyzed Cou p lin g Rea ction of Meth yl (Z)-
3-Iod op r op en oa te w ith Or ga n ozin c F or m ed by th e Re-
a ction of 1-P h en ylh ex-1-yn e w ith n -Bu Li a n d Zn Br 2 in
th e P r esen ce of HgCl2. To a solution of HgCl2 (3 mg, 0.011
mmol, 1.5 mol %) and 1-phenylhex-1-yne (134 mg, 0.85 mmol)
in THF (2 mL) in a dry Schlenk tube was added n-BuLi (0.7
mL, 1.6 M in hexane, 0.94 mmol) at rt under N2. After 100
min at rt, dry ZnBr2 (278 mg, 1.275 mmol) in THF (3 mL) was
added at -78 °C. After 10 min at this temperature, the
reaction mixture was warmed to room temperature and stayed
at rt for 20 min, and then Pd(PPh3)4 (29 mg, 0.025 mmol) and
methyl (Z)-3-iodopropenoate (106 mg, 0.5 mmol) in THF (1 mL)
were added at rt. After the reaction was complete, as moni-
tored by TLC (eluent: petroleum ether/ethyl acetate ) 100:
1), it was quenched with water and extracted with ether.
Drying over MgSO4, rotary evaporation, and chromatography
on silica gel (eluent: petroluem/ethyl acetate ) 100:1) afforded
103 mg (85%) of methyl 4-phenylnona-2(E),4,5-trienoate ((E)-
7b): 1H NMR 7.35-7.15 (m, 6H), 6.43 (s, 1H), 5.95 (d, J )
15.84 Hz, 1H), 3.75 (s, 3H), 2.35-2.20 (m, 2H), 1.70-1.50 (m,
2H), 1.00 (t, J ) 7.24 Hz, 3H); MS m/e 242 (M+, 8.94), 153
(100); IR (neat) 1922, 1714, 1618, 1192, 1172 cm-1; HRMS
calcd for C16H18O2 242.1302, found 242.1290.
mmol) and 2d (113 mg, 0.5 mmol) to afford 99 mg (77%) of
(Z)-7d : 1H NMR 7.45-7.10 (m, 5H), 6.50 (s, 1H), 5.90 (s, 1H),
3.75 (s, 3H), 2.45-2.20 (m, 5H), 1.70-1.45 (m, 2H), 0.95 (t, J
) 7.30 Hz, 3H); MS m/e 256 (M+, 27.87), 43 (100); IR (neat)
1930, 1720, 1620, 1170 cm-1; HRMS calcd for C17H20O2
256.1458, found 256.1490.
Meth yl 3,4-diph en yln on a-2(Z),4,5-tr ien oate ((Z)-7e) was
prepared similarly, starting from 6 (134 mg, 0.85 mmol) and
2e (143 mg, 0.5 mmol) to afford 71 mg of 2e and 37 mg (47%,
based on 50% conversion) of (Z)-7e: 1H NMR 7.35-7.05 (m,
10H), 6.12 (s, 1H), 6.07 (s, 1H), 3.55 (s, 3H), 2.45-2.30 (m,
2H), 1.70-1.50 (m, 2H), 1.00 (t, J ) 7.3 Hz, 3H); MS m/e 318
(M+, 27.87), 289 (100); IR (neat) 1945, 1730, 1615, 1180, 1160
cm-1; HRMS calcd for C22H22O2 318.1614, found 318.1651.
Isom er iza tion Rea ction of Eth yl 6-P h en ylh ex-5-yn -
2(Z)-en oa te ((Z)-4a ). (Z)-4a (30 mg, 0.14 mmol) was added
to DMF (1 mL) in a dry Schlenk tube and heated to 50 °C.
After 2 h at this temperature, the reaction mixture was
extracted with ether and washed with water. After the mixture
was dried over MgSO4, rotary evaporation afforded 26 mg of
a mixture of ethyl 6-phenylhex-5-yn-3(Z)-enoate ((Z)-5a ) and
ethyl 6-phenylhex-5-yn-3(E)-enoate ((E)-5a ) in a ratio of 1:4.
P d (P P h 3)4-Ca ta lyzed Cou p lin g Rea ction of Eth yl (Z)-
3-Iod op r op en oa te a n d P h en yl Iod id e w ith Or ga n ozin c
F or m ed by th e Su bsequ en t Rea ction of 1-P h en ylp r op -
1-yn e w ith n -Bu Li a n d Zn Br 2 in th e P r esen ce of HgCl2.
To a solution of HgCl2 (3 mg, 0.011 mmol, 1.5 mol %) and
1-phenylprop-1-yne (99 mg, 0.85 mmol) in THF (2 mL) in a
dry Schlenk tube was added n-BuLi (0.7 mL, 1.6 M in hexane,
0.94 mmol) at -78 °C under N2. After 100 min at -78 °C, dry
ZnBr2 (278 mg, 1.275 mmol) in THF (3 mL) was added. After
10 min at this temperature, the reaction mixture was warmed
to room temperature and stayed at rt for 20 min, and then
Pd(PPh3)4 (29 mg, 0.025 mmol), ethyl (Z)-3-iodopropenoate (113
mg, 0.5 mmol), and phenyl iodide (102 mg, 0.5 mmol) in THF
(1 mL) were added at rt. After the reaction was complete, as
monitored by TLC (eluent: petroleum ether/ethyl acetate )
100:1), it was quenched with water and extracted with ether.
the mixture was dried over MgSO4, rotary evaporation afforded
1,1-diphenylpropa-1,2-diene5 and ethyl 6-phenylhex-5-yn-2(Z)-
enoate ((Z)-4a ) in an NMR ratio of 4:1.
Isom er iza tion of Eth yl 6-P h en ylh ex-5-yn -2(E)-en oa te.
To a solution of 1-phenylprop-1-yne in THF (1 mL) in a dry
Schlenk tube was added n-BuLi at -78 °C under N2. After
100 min at -78 °C, dry ZnBr2 (for the specific amounts of all
the reagents in this procedure see Scheme 4) in THF (2 mL)
was added. After 10 min at this temperature, the reaction
mixture was warmed to room temperature and stayed at rt
for 20 min, a solution of ethyl 6-phenylhex-5-yn-2(E)-enoate
(53 mg, 0.25 mmol) in THF (1 mL) was added at the temper-
ature specified in Scheme 4. After the reaction was complete
as monitored by TLC, it was quenched with water and
extracted with ether. Drying over MgSO4 and rotary evapora-
tion afforded the crude product, which was analyzed by 300
MHz 1H NMR spectra using CH2Br2 as the internal standard.
Ack n ow led gm en t. We thank the National Natural
Science Foundation of China, Chinese Academy of
Sciences, and Shanghai Municipal Committee of Sci-
ences and Technology for financial support. S.M. thanks
the Hong Kong Qiu Shi Foundation of Science and
Technology for the 1999 Qiu Shi Award for Young
Scientific Workers (1999-2003).
Eth yl 4-p h en yln on a -2(E),4,5-tr ien oa te ((E)-7a ) was pre-
pared similarly, starting from 6 (134 mg, 0.85 mmol) and 2c
(113 mg, 0.5 mmol) to afford 110 mg (86%) of (E)-7a : 1H NMR
7.40-7.20 (m, 6H), 6.43 (s, 1H), 5.95 (dd, J ) 15.8, 1.5 Hz,
1H), 4.20 (q, J ) 7.1 Hz, 2H), 2.35-2.20 (m, 2H), 1.70-1.50
(m, 2H), 1.30 (t, J ) 7.1 Hz, 3H), 1.00(t, J ) 7.4 Hz, 3H); 13C
NMR 212.23, 166.75, 143.29, 133.27, 128.76, 128.40, 128.07,
118.13, 108.26, 96.19, 60.35, 30.75, 20.92, 14.30, 13.97; MS
1
Su p p or tin g In for m a tion Ava ila ble: The H NMR spec-
tra of the compounds 3a , (Z)-4a , (E)-4a , (Z)-5a , (E)-5a , (Z)-
4b, (E)-5b, (Z)-4e, (Z)-4f, (E)-7a , (E)-7b, (Z)-7d , and (Z)-7e,
1
2D H-1H NOSEY spectra of (Z)-7d , HMBC spectra of (Z)-4a
and (Z)-5a , and detailed information for the X-ray structure
determination of (E)-5b. This material is available free of
charge via the Internet at http://pubs.acs.org.
m/e 256 (M+, 14.75), 183 (100); IR (neat) 1930, 1715, 1620 cm-1
;
HRMS calcd for C17H20O2 256.1458, found 256.1463.
Meth yl 3-m eth yl-4-p h en yln on a -2(Z),4,5-tr ien oa te ((Z)-
7d ) was prepared similarly, starting from 6 (134 mg, 0.85
J O991243G