The Stille Reaction of 1,1-Dibromo-1-alkenes: Preparation of Trisubstituted Alkenes and Internal Alkynes

Article abstract of DOI:10.1021/jo991116k

The Stille reaction of 1,1-dibromo-1-alkenes 1 with aryl- and vinylstannanes produces different products depending on the reaction conditions. When the reaction is run in toluene or 1,4-dioxane with tris(2-furyl)phosphine (TFP) as the ligand, (Z)-bromoalkenes 2 are obtained stereospecifically in good to excellent yields with most substrates. However, 2-aryl-1,1-dibromo-1-alkenes (1e,1g) having an electron-donating methoxy group in the para- or ortho- position give poor yields. This method has been applied to the one-pot syntheses of stereospecifically trisubstituted alkenes 5. When the Stille reaction is conducted in a highly dipolar solvent (DMF), monobromides 2 and/or internal alkynes 4 are the products. The less reactive phenylstannane favors the formation of alkynes 4, regardless of which ligand is used. More reactive organostannanes (vinyl, furyl) require a very electron rich ligand, tris(4-methoxyphenyl)phosphine, for the formation of alkynes 4. This new method for internal alkyne preparation is general, requires very mild reaction conditions, and gives high yields.

Full text of DOI:10.1021/jo991116k

J . Org. Chem. 1999, 64, 8873-8879
8873
Th e Stille Rea ction of 1,1-Dibr om o-1-a lk en es: P r ep a r a tion of
Tr isu bstitu ted Alk en es a n d In ter n a l Alk yn es
Wang Shen* and Le Wang
Cancer Research, Pharmaceutical Products Division, Abbott Laboratories,
Abbott Park, Illinois 60064-6101
Received J uly 12, 1999
The Stille reaction of 1,1-dibromo-1-alkenes 1 with aryl- and vinylstannanes produces different
products depending on the reaction conditions. When the reaction is run in toluene or 1,4-dioxane
with tris(2-furyl)phosphine (TFP) as the ligand, (Z)-bromoalkenes 2 are obtained stereospecifically
in good to excellent yields with most substrates. However, 2-aryl-1,1-dibromo-1-alkenes (1e,1g)
having an electron-donating methoxy group in the para- or ortho- position give poor yields. This
method has been applied to the one-pot syntheses of stereospecifically trisubstituted alkenes 5.
When the Stille reaction is conducted in a highly dipolar solvent (DMF), monobromides 2 and/or
internal alkynes 4 are the products. The less reactive phenylstannane favors the formation of alkynes
4, regardless of which ligand is used. More reactive organostannanes (vinyl, furyl) require a very
electron rich ligand, tris(4-methoxyphenyl)phosphine, for the formation of alkynes 4. This new
method for internal alkyne preparation is general, requires very mild reaction conditions, and gives
high yields.
In tr od u ction
halides has gained wide acceptance in synthetic organic
chemistry due to the mild reaction conditions and easy
preparation of organostannanes. Because the Stille chem-
istry is compatible with virtually any functional group,
and also because organostannanes are stable to many
reaction conditions, the Stille reaction is ideal in syn-
thesis of complex natural products.8 However, few studies
of the Stille reaction of 1,1-dibromo-1-alkenes have been
reported despite the advantages this approach may
provide over the existing methods.9 The successful in-
tramolecular cross-coupling of 1,1-dibromo-1-alkenes with
organostannanes was reported,10 and the reaction pro-
ceeded with stereoselective coupling of the (Z)-bromide
with an internal directing group but failed in the absence
of the directing group.10a More recently, Uneshi and co-
workers demonstrated that the (E)-bromides in 1,1-
dibromo-1-alkenes could be selectively reduced by tribu-
tyltin hydride using tetrakis(triphenylphosphine)palladium
as the catalyst.11 Only one example of the intermolecular
Stille reaction of 1,1-dibromo-1-alkenes has been reported
previously.12 Specifically, â,â-dibromostyrene and 1-pro-
1,1-Dibromo-1-alkenes are easily prepared,1 and they
can provide a convenient and straightforward route for
the preparation of stereospecifically trisubstituted alk-
enes by palladium-catalyzed stepwise coupling of both
bromides.2 The rates of palladium-catalyzed cross-
coupling reactions of (E)- and (Z)-1-bromo-1-alkenes are
substantially different.3 Palladium-catalyzed stereose-
lective monosubstitutions of 1,1-dihalo-1-alkenes (halo as
chloride and bromide) with Grignard, and organozinc
reagents,4 organoalanes,5 and organoboronic acids6 have
been reported. However, the use of organoaluminum,
Grignard and organozinc reagents is limited by their
difficulty in preparation and incompatibility with many
functional groups. Coupling of vinylboronic acids with
1,1-dibromo-1-alkenes gives good yields with highly toxic
thallium(I) hydroxide6a,b but only poor to moderate yields
with other bases.6c Moreover, the coupling of less reactive
arylboronic acids with 1,1-dibromo-1-alkenes has not
been demonstrated.
The Stille reaction7 of organostannanes with organo-
(8) Examples: (a) Lankacidin C: Kende, A. S.; Koch, K.; Dorey, G.;
Kaldor, I.; Liu, K. J . Am. Chem. Soc. 1993, 115, 9842. (b) Rapamycin:
Nicolaou, K. C.; Piscopio, A. D.; Bertinato, P.; Chakrabarty, T. K.;
Minowa, N.; Koide, K. Chem. Eur. J . 1995, 1, 318. (c) Dynemicin A:
Shair, M. D.; Yoon, T.; Chao, T.-C.; Danishesky, S. J . Angew. Chem.,
Int. Ed. Engl. 1994, 33, 2477. (d) Eleutherobin: Chen, X.-O., Zhou,
B.; Bhattacharya, S. K.; Gutteridge, C. E.; Pettus, T. R. R.; Danishesky,
S. J . Angew. Chem., Int. Ed. Engl. 1998, 37, 789.
(9) The related coupling of dichloroimines with alkynyltin fails to
stop at the monoalkynylation stage: (a) Ito, Y.; Inouye, M.; Yokota,
H.; Murakami, M. J . Org. Chem. 1990, 55, 2567. (b) Ito, Y.; Inouye,
M.; Yokota, H.; Murakami, M. Tetrahedron Lett. 1988, 29, 5379.
(10) (a) Nuss, J . M.; Rennels, R. A.; Levine, B. H. J . Am. Chem. Soc.
1993, 115, 6991. (b) Torii, S.; Okumoto, H.; Tadokodo, T.; Nishimura,
A.; Rashid, M. A. Tetrahedron Lett. 1993, 34, 2139. (c) Trost, B. M.;
Walchli, R. J . Am. Chem. Soc. 1987, 109, 3487.
(1) (a) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 3769. (b)
Ramirez, F.; Desai, N. B.; McKelvie, N. J . Am. Chem. Soc. 1962, 84,
1745.
(2) General references of palladium chemistry: (a) Tsuji, J . Pal-
ladium Reagents and Catalysts; J ohn Wiley: Chichester, U.K., 1995.
(b) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic
Press: London, 1985.
(3) Rossi, R.; Carpita, A. Tetrahedron Lett. 1986, 27, 2529.
(4) (a) Minato, A.; Suzuki, K.; Tamao, K. J . Am. Chem. Soc. 1987,
109, 1257. (b) Minato, A. J . Org. Chem. 1991, 56, 4052. (c) Panek, J .
S.; Hu, T. J . Org. Chem. 1997, 62, 4912.
(5) Ratovelomanana, V.; Hammoud, A.; Linstrumelle, G. Tetrahe-
dron Lett. 1987, 28, 1649.
(6) (a) Roush, W. R.; Moriarty, K. J .; Brown, B. B. Tetrahedron Lett.
1990, 31, 6509. (b) Roush, W. R.; Koyama, K.; Curtin, M. L.; Moriarty,
K. J . J . Am. Chem. Soc. 1996, 118, 7502. (c) Baldwin, J . E.; Chesworth,
R.; Paker, J . S.; Russell, A. T. Tetrahedron Lett. 1995, 36, 9551.
(7) Reviews of the Stille reactions: (a) Stille, J . K. Angew. Chem.,
Int. Ed. Engl. 1986, 25, 508. (b) Farina, V.; Krishnamurthy, V.; Scott,
W. J . Org. React. 1997, 50, 1. (c) Mitchell, T. N. In Metal-catalyzed
Cross-coupling Reactions; Diederich, F., Stang, S., Eds.; Wiley-VCH:
Weinheim, Germany, 1998; Chapter 4.
(11) (a) Uenishi, J .; Kawahama, R.; Yonemitsu, O. J . Org. Chem.
1996, 61, 5716. (b) Uenishi, J .; Kawahama, R.; Shiga, Y.; Yonemitsu,
O. Tetrahedron Lett. 1996, 37, 6759. (c) Uenishi, J .; Kawahama, R.;
Yonemitsu, O.; Tsuji, J . J . Org. Chem. 1998, 63, 8965. (d) Uenishi, J .;
Kawahama, R.; Yonemitsu, O.; Wada, A.; Ito, M. Angew. Chem., Int.
Ed. Engl. 1998, 37, 320.
(12) Zapata, A. J .; Ruiz, J . J . Organomet. Chem. 1994, 479, C6.
10.1021/jo991116k CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/03/1999

8874 J . Org. Chem., Vol. 64, No. 24, 1999
Ta ble 1. Solven t a n d Liga n d Effects
Shen and Wang
entry
solvent
ligand
TFP
TFP
Ph3P
Ph3As
(o-Tol)3P
dppf
(4-MeOPh)3P
TFP
PhSnMe3 (equiv)
basea
none
none
none
none
none
none
none
none
none
none
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
T (°C)
t (h)
1a :2a :3a :4a (yield, %)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
Dioxane
MeCN
DMF
1.05
2.2
100
105
100
100
100
100
100
100
100
80
20
48
20
20
20
20
20
20
20
10
10
10
10
10
48
0:92:8:0 (98)c
3a only (100)
77:4:1:18
1.05
1.05
1.05
1.05
1.05
1.05
1.05
2.2
1.05
1.05
1.05
1.05
1.05
31:37:32:0
1a only (no rxn)
1a only (no rxn)
1a only (no rxn)
0:90:10:0 (93)
46:27:7:21
4a only (92)
4a only (91)
4a only (88)
4a only (88)
0:0:26:74 (19%)
1a only (no rxn)e
TFP
TFP
TFP
DMF
DMF
DMF
DMF
80
80
80
80
(4-MeOPh)3P
Ph3P
MeCNd
TFP
DMF
80
1.5 equiv when used. Yields were isolated; product ratios were determined by GC. c GC showed that product 3a appeared early with
a
b
d
2a , and 1.05 equiv of PhSnMe3 was needed to completely consume 1a . Pd(MeCN)2Cl2 (5 mol %) was used without an added ligand; see
ref 12. e No Pd was added to the reaction; see also ref 12.
penyltributyltin react to give an enyne product in 39%
yield (eq 1).
of the chosen ligand (7.5% if bidentate). With tris(2-furyl)-
phosphine (TFP) or triphenylarsine as the ligand, the
coupling proceeded without the formation of alkyne 4a .
TFP efficiently catalyzed the stereospecifical cross-
coupling of the (E)-bromide with trimethyl(phenyl)tin to
give (Z)-monobromide 2a in excellent yield (entry 1, Table
1). The coupling of both (E)- and (Z)-bromides to form
diphenylated product 3a required a higher temperature
and a longer reaction time (entry 2). Triphenylarsine
yielded a considerable amount of 3a in addition to
remaining 1a (entry 4), as the formation of 3a consumed
2 equiv of trimethyl(phenyl)tin. When triphenylphos-
phine was used (entry 3), most 1a remained, and alkyne
4a was the major product observed. Other ligands
(entries 5-7) gave no reaction at all in toluene. Appar-
ently, a “soft” ligand, such as TFP or Ph3As, which
facilitates the transmetalation step is required for the
reaction to succeed in toluene.14 TFP is superior to Ph3-
As because of the selectivity.
Next, the solvent effect was examined (entries 8-10,
Table 1). In 1,4-dioxane, a low polarity solvent, the
reaction gave a similar yield and ratio of products to those
obtained with toluene. Acetonitrile afforded about equal
amounts of alkyne 4a and monobromide 2a , along with
unreacted 1a and small amount of diphenylated product
3a . When DMF, a highly dipolar and good coordinating
solvent, was used (entries 10-13), only alkyne 4a formed.
The reaction in DMF required a shorter time and a lower
temperature. Because the formation of alkyne 4a is
accompanied by generation of HBr, 2 equiv of trimethyl-
(phenyl)tin is needed to complete the reaction (entry 10).
The addition of N,N-diisopropylethylamine (DIPEA, en-
tries 11-13) resulted in the requirement of only slightly
more than 1 equiv of the stannane.
Previously, we reported the synthesis of isocoumarins
via a palladium-catalyzed tandem Stille reaction and
subsequent annulation of methyl 2-(2′,2′-dibromovinyl)-
benzoates (eq 2).13 In this paper, we report that the Stille
reaction of 1,1-dibromo-1-alkenes (1) can occur stereospe-
cifically to produce the desired (Z)-monobromides in good
yields. More importantly, we also demonstrate that 1,1-
dibromo-1-alkenes may form internal alkynes in excellent
yields under slightly varied reaction conditions.
Resu lts a n d Discu ssion
A. In vest iga t ion of R ea ct ion Con d it ion s. The
reported unsuccessful intermolecular Stille reaction12 of
1,1-dibromo-1-alkenes prompted us to carry out a sys-
tematic investigation to determine alternative conditions
for the proposed reaction (Table 1). Methyl 4-(2′,2′-
dibromovinyl)benzoate (1a ) was chosen as a model sub-
strate to couple with trimethyl(phenyl)tin due to the ease
of monitoring the reaction by TLC and to the ease of
separating the products by flash chromatography as
compared with â,â-dibromostyrene. The product ratios
were determined by gas chromatography using an inter-
nal standard (1,3,5-tri-tert-butylbenzene).
First, different ligands were examined while stirring
the reaction mixture under an atmosphere of nitrogen
at 100 °C in toluene. Unless otherwise noted, tris-
(dibenzylideneacetone)dipalladium (Pd2dba3, 2.5 mol %)
was used as the palladium source, along with 15 mol %
Other highly dipolar solvents (not reported in Table
1), such as DMSO, HMPA, 1-methyl-2-pyrolidinone (NMP),
and N,N-dimethylacetamide (DMA), also give 4a as the
only product in good yields under similar reaction condi-
tions to entry 11. When the reaction was run in DMF
under similar reaction conditions to entry 11, all of the
(13) Wang, L.; Shen, W. Tetrahedron Lett. 1998, 39, 7625.
(14) Farina, V.; Krishnan, B. J . Am. Chem. Soc. 1991, 113, 9585.

The Stille Reaction of 1,1-Dibromo-1-alkenes
J . Org. Chem., Vol. 64, No. 24, 1999 8875
phosphine ligands surveyed (entries 12, 13, and others15
not listed in Table 1) gave alkyne 4a in good yields.
Finally, when the reaction was run with Pd(MeCN)2Cl2,
without using an added alternative ligand, as reported
in the literature,12 a poor yield of a 1:3 mixture of 3a and
4a was obtained (entry 14). In a control experiment, 1a
remained unchanged after prolonged heating if the
reaction was run without palladium but with a ligand
(TFP) and DIPEA in DMF (entry 15).
Ta ble 2. Mon osu bstitu tion of 1,1-Dibr om o-1-a lk en es
B. Ster eosp ecifica l Mon ocou p lin g of 1,1-Dibr om o-
1-a lk en es. A variety of 1,1-dibromo-1-alkenes 1 (1.0
mmol) were coupled with different stannanes, using 2.5
mol % Pd2(dba)3 and 15 mol % TFP in toluene (5.0 mL)
at 100 °C for 20 h, as shown in Table 2. Most 2-aryl- and
2-alkyl-1,1-dibromo-1-alkenes gave monobromides 2 in
good yields, with no to small amount of biscoupled
products 3 isolated. Substitutions at different positions
of the aromatic ring (entries 4-6) by the electron-
withdrawing cyano group did not affect the reaction.
However, because the methoxy group at ortho or para
position in 1e or 1g (entries 7, 9) conjugatively donates
electron to the alkene bond, the oxidative insertion by
Pd(0) into the C-Br bond becomes more difficult. Con-
sequently, the reactions required more stannane and
resulted in lower yields and mixtures of products. On the
other hand, the methoxy group at the meta position (1f)
cannot conjugatively donate electrons to the alkene bond,
and a satisfactory coupling result was obtained (entry
8).
The significant amounts of diphenylated products 3j,n
could be attributed to the weak directing effect of oxygen
atoms in 1g,j, as shown in Scheme 1. Coordination of
palladium(0) to the oxygen atoms prior to the oxidative
insertion leads to the formation of reversed (E)-mono-
bromides 2jr and 2n r , which were further phenylated
to give the minor products 3j,n .
C. Syn th esis of In ter n a l Alk yn es. As shown in
entries 11 and 12 of Table 1, when the coupling reactions
of dibromides 1 (1.0 mmol) with PhSnMe3 (1.05 mmol)
were performed in DMF at 80 °C for 10 h, alkynes 4 were
the product. DIPEA (1.5 mmol) was used to neutralize
hydrogen bromide generated from the reaction. The
results are summarized in Table 3.
Internal alkynes 4 always resulted when trimethyl-
(phenyl)tin was used, and the phosphine ligands had
little effect on the coupling (entries 11-13, Table 1;
entries 17, 18, Table 3). However, when reactive stan-
nanes, such as vinyltributyltin16 and 2- and 3-furyltribu-
tyltin were coupled using the TFP ligand, monobromides
2 were obtained exclusively or partly (entries 1, 3, 5, 19,
Table 3) instead of the expected alkynes 4. It was found
that a very electron rich ligand, tris(4-methoxyphenyl)-
phosphine, which promotes much slower transmetalation
than TFP,14 suppressed the formation of monobromides
2 completely to give alkynes 4 in good yields. Other
palladium ligands, such as triphenylphosphine, tricyclo-
hexylphosphine, dppf, and tri-o-tolylphosphine give a
mixture of both products 2 and 4 in varied ratios.
Alkyne formation is unaffected by the electronic char-
acter or position of substituents on 1,1-dibromoalkenes
(15) Other ligands: triphenyl phosphite; tri-o-tolylphosphine; tri-
cyclohexylphosphine; dppp; dppf.
(16) The rate of transmetalation correlates with the electronegativity
of the organometallica. The relative rates of selected stannane trans-
metalations: Labadie, J . W.; Stille, J . K. J . Am. Chem. Soc. 1983, 105,
6129.
a
b
1.5 equiv of PhSnMe3 was used. Ratio was determined by
1H NMR integration. c 1.2 equiv of PhSnMe3 was used.

8876 J . Org. Chem., Vol. 64, No. 24, 1999
Shen and Wang
carbenoid intermediate1,18 (path A) or the formation of
alkynyl bromide 8 (path B) from cis â-hydrogen elimina-
tion of intermediate 6 (Scheme 2).
Sch em e 1
However, these hypotheses are not consistent with the
observation illustrated in eqs 4 and 5. The reaction of
alkyne 7a and trimethyl(phenyl)tin did not yield 4a even
in the presence of one equivalent of bis(triphenylphos-
phine)palladium(II) dibromide (eq 4). No identifiable
product was isolated from the reaction, though alkyne
7a was totally consumed. On the other hand, when (E)-
bromoalkene 919 was subjected to the reaction conditions,
dehydrobromination did not ocuur as path B suggested
(eq 5).
A working hypothesis is proposed in Scheme 3. In a
highly dipolar, coordinating solvent such as DMF, com-
plex 6, formed from initial oxidative insertion by Pd(0)
into 1, may undergo ligand/solvent exchange to form
complex 10.17b The Pd-C bond in 6, and especially in 10,
is polarized by the solvent, which may lead to the
formation of palladium carbenoid 11 (path C).20,21 The
highly dipolar solvent also stabilizes complex 11, which
favors its formation. Rearrangement of 11 results in the
formation of complex 12, which loses HBr to form alkynyl
palladium species 13. Alternatively, elimination of HBr
from either complex 6 or 10 could also occur to give
complex 13 (path D). Coupling of 13 with a stannane
affords alkyne 4.
The rate of transmetalation determines the formation
of either monobromides 2 or internal alkynes 4. When
trimethyl(phenyl)tin, a slow transmetalating stannane
is used in the Stille reaction in a highly dipolar solvent,
alkynes 4 are the product regardless of which ligand is
used. When fast transmetalating organostannanes, such
as 2-(tributylstannyl)furan and tributyl(vinyl)tin, are
used in the reaction, monobromides 2 are formed even
in DMF with the TFP ligand (path E). On the other hand,
a very electron rich ligand, tris(4-methoxyphenyl)phos-
phine, promotes much slower transmetalation than TFP
and leads to the exclusive formation of alkynes 4 regard-
less of which stannane is used.
1. Thus, 2-aryl-1,1-dibromo-1-alkenes (1b-g) bearing
either the electron-donating methoxy group or the electron-
withdrawing cyano group at ortho, meta, and para
positions (entries 7-12, Table 3) afforded good yields of
the corresponding alkynes. As reported in the literature,17a
we also observed that a highly dipolar solvent accelerates
the Stille reaction (Table 4, entries 1-3). This may
explain the observation that, contrary to the formation
of monobromides 2h ,j, dibromides 1e,g give good yields
of alkynes 4h ,j, as the solvent effect offsets the conjuga-
tive electron donation by the methoxy group to allow the
reactions to proceed smoothly.
D. Syn th esis of Tr isu bstitu ted Alk en es. Trisubsti-
tuted alkenes 3 and 5 could be synthesized from mono-
bromides 2 by coupling of the remaining bromide (method
A, Table 4), and the reactions are faster in DMF than in
toluene with similar yields (entries 1, 2). Alternatively,
the preparation of 5 could be accomplished by an one-
pot process of sequential coupling of (E)- and (Z)-bromides
in 1 with two different stannanes (method B, Table 4) in
toluene.
When monobromide 2a was reacted with trimethyl-
(phenyl)tin in DMF, products resulting from both the
methyl (5a ) and phenyl transfer (3a ) were obtained.
However, product 3a was obtained cleanly from the
coupling of 2a with trimethyl(phenyl)tin in toluene (entry
2) or with tributyl(phenyl)tin in DMF (entry 1).17 Product
5a was synthesized quantitatively by coupling 2a with
tetramethyltin in DMF (entry 4).
E. Mech a n istic Con sid er a tion s. In their coupling
of â,â-dibromostyrene with 1-propenyltributyltin (eq 1),
Zapta and co-workers reported that the two substrates
reacted at room temperature to afford the corresponding
enyne without a palladium catalyst or other additives.12
However, dibromide 1a did not react with trimethyl-
(phenyl)tin in DMF in the absence of palladium, even at
elevated temperature for prolonged time (entry 15, Table
1). Furthermore, alkynes 4 are not derived from the
monobromides 2, as 2a remained unchanged when
heated with the catalyst (eq 3).
Con clu sion s
We determined that the Stille coupling of 1,1-dibromo-
(17) Similar solvent and stannane effects were observed previ-
ously: (a) Echavarren, A. M.; Stille, J . K. J . Am. Chem. Soc. 1987,
109, 5478. (b) Farina, V.; Krishnan, B.; Marshall, D. R.; Roth, G. P. J .
Org. Chem. 1993, 58, 5434.
(18) Braun, M. Angew. Chem., Int. Ed. Engl. 1998, 37, 430.
(19) (a) Kolodiazhnyi, O. I. Tetrahedron 1996, 52, 1855. (b) Speziale,
A. J .; Ratts, K. W. J . Org. Chem. 1963, 28, 465.
(20) Palladium(II) carbenoid is well-known in palladium-catalyzed
cyclopropanations: (a) Paulissen, R.; Hubert, A. J .; Teyssie, Ph.
Tetrahedron Lett. 1972, 1465. (b) Doyle, M. P.; Wang, L. C.; Loh, K.-
L. Tetrahedron Lett. 1984, 25, 4087.
(21) Palladium(0) carbenoid is the intermediate in anomalous cine
substitution in the Stille couplings: (a) Busacca, C. A.; Swestock, J .;
J ohnson, R. E.; Bailey, T. R.; Musza, L.; Rodger, C. A. J . Org. Chem.
1994, 59, 7553. (b) Farina, V.; Hossain, M. A. Tetrahedron Lett. 1996,
37, 6997.
Other possible mechanisms for the formation of alkynes
4 involve the formation of terminal alkyne 7 through a

The Stille Reaction of 1,1-Dibromo-1-alkenes
J . Org. Chem., Vol. 64, No. 24, 1999 8877
Ta ble 3. Syn th eses of Alk yn es 4 fr om 1,1-Dibr om oa lk en es 1
a
Reaction was performed on a 1.0 mmol scale.

8878 J . Org. Chem., Vol. 64, No. 24, 1999
Ta ble 4. Syn th eses of Tr isu bstitu ted Alk en es
Shen and Wang
a
b
On 1.0 mmol scale. Method A: monobromide 2a (1.0 mmol) and a stannane (1.1 mmol) were stirred with Pd2dba3 (0.025 mmol) and
TFP (0.15 mmol). Method B: dibromide 1 (1.0 mmol) and stannane 1 (1.05 mmol) were stirred with Pd2dba3 (0.025 mmol) and TFP (0.15
mmol) in toluene at 100 oC until TLC indicated the disappearance of 1 (reaction time t1). Stannane 2 (1.1 mmol) was added, along with
more catalyst (0.025 mmol of Pd2dba3, 0.15 mmol of TFP), and the reaction was continued at 100 oC (reaction time t2).
Sch em e 2
low to nonpolar solvents with the TFP ligand. The
reaction is less suitable for 2-aryl-1,1-dibromo-1-alkenes
bearing strongly electron donating groups at ortho or
para positions. This methodology can be applied to the
stereospecifical syntheses of trisubstituted alkenes, in-
cluding synthetically important 1,3-dienes (2d ,l,q,5d ,e).
We also developed an alternative method for the
preparation of internal alkynes 4. The formation of
alkynes using the Stille reaction of 1,1-dibromo-1-alkenes
in a highly dipolar solvent represents a new, general,
mild, and high-yielding method to prepare this important
class of compounds.
1-alkenes 1 with organostannanes gave good to high
yields of monobromides 2 when the reactions were run in

The Stille Reaction of 1,1-Dibromo-1-alkenes
J . Org. Chem., Vol. 64, No. 24, 1999 8879
phosphine (0.15 mmol) in DMF (5 mL) was flushed with
nitrogen and heated at 80 °C for 10 h. The reaction mixture
was diluted with ether, washed with water, dried over
anhydrous magnesium sulfate, filtered, and concentrated. The
residue was purified by column chromatography. If necessary,
the products were further purified by recrystallization from
ethanol to give analytically pure samples.
Sch em e 3
Meth yl 4-(2-P h en yleth yn yl)ben zoa te (4a ): 1H NMR (400
MHz, CDCl3) δ 7.98 (td, J ) 1.7, 8.5 Hz, 2H), 7.55 (td, J ) 1.7,
8.5 Hz, 2H), 7.52 (m, 2H), 7.32 (m, 3H), 3.87 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 166.3, 131.6, 131.3, 129.35, 129.33, 128.6,
128.3, 127.9, 122.6, 92.3, 88.5, 52.0. Anal. Calcd for C16H12O2:
C, 81.34; H, 5.12. Found: C, 81.06; H, 5.24.
Gen er a l P r oced u r e A for th e P r ep a r a tion of Tr isu b-
stitu ted Alk en es 5 fr om Mon obr om id e 2a . A solution of
2a (1.0 mmol), a stannane (1.1 mmol), Pd2dba3 (0.025 mmol),
and TFP (0.15 mmol) in DMF (5 mL) was flushed with nitrogen
and heated at 80 °C for 10 h. The reaction mixture was then
diluted with ether, washed with water 3 times, dried over
anhydrous magnesium sulfate, filtered, and concentrated. The
residue was purified by column chromatography. If necessary,
the products were further purified by recrystallization from
ethanol to give analytically pure samples.
Met h yl 4-[(E)-2-Met h yl-2-p h en ylvin yl]b en zoa t e (5a ):
1H NMR (400 MHz, CDCl3) δ 8.02 (td, J ) 1.7, 8.5 Hz, 2H),
7.49 (m, 2H), 7.39 (d, J ) 8.2 Hz, 2H), 7.35 (m, 2H), 7.28 (m,
1H), 6.81 (s, 1H), 3.88 (s, 3H), 2.26 (d, J ) 1.2 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 166.8, 143.4, 142.9, 139.5, 129.4,
128.9, 128.3, 127.9, 127.5, 126.7, 125.9, 51.9, 17.6. Anal. Calcd
for C17H16O2: C, 80.93; H, 6.39. Found: C, 80.81; H, 6.44.
Gen er a l P r oced u r e B for th e P r ep a r a tion of Tr isu b-
stitu ted Alk en es 5 fr om Dibr om id es 1. A solution of a
starting dibromide 1 (1.0 mmol), the first stannane (1.05
mmol), Pd2dba3 (0.025 mmol), and TFP (0.15 mmol) in toluene
(5 mL) was flushed with nitrogen twice and heated at 100 °C
until the starting dibromide was completely consumed. Then,
the second stannane (1.1 mmol) was added to the reaction
mixture, along with more Pd2dba3 (0.025 mmol) and TFP (0.15
mmol). The reaction was further heated at 100 °C until the
intermediate monobromide was consumed. The reaction mix-
ture was filtered through silica gel and rinsed with 20% ether
in hexane. The filtrate was concentrated and purified by
column chromatography. If necessary and feasible, the prod-
ucts were further purified by recrystallization from ethanol
to give analytically pure samples.
Exp er im en ta l Section
Gen er a l Meth od s. All reagents were commercially avail-
able and were used without further treatment. All solvents
were commercial anhydrous solvents from Aldrich. 1H NMR
spectra were recorded at 300 MHz (75 MHz for 13C) and 400
MHz (100 MHz for 13C). Elemental analyses were performed
by Robertson Microlit Laboratories, Inc., of Madison, NJ .
Column chromatography was performed on Merck silica gel
60. All reactions were performed under nitrogen atmosphere.
Gen er a l P r oced u r es for th e P r ep a r a tion of Sta r tin g
Dibr om id es 1. To a 0 °C solution of an aldehyde (10.0 mmol)
and carbon tetrabromide (10.5 mmol) in dichloromethane (30
mL) was added triphenylphosphine (21.0 mmol) in 4 portions
at 3 min intervals. The reaction was then stirred for 1 h at 25
°C. Hexane was added to the reaction mixture with good
stirring, and the resulting slurry was filtered through silica
gel and rinsed twice with a mixed solvent of hexane and ether
(1/1). The crude product after evaporation of the filtrate was
then recrystallized from ethyl acetate/hexane (if solid) or
purified with column chromatography by dichloromethane/
hexane (if liquid). Yields are in the range of 85-100%.
Meth yl 4-(2,2-Dibr om ovin yl)ben zoa te (1a ): 1H NMR
(300 MHz, CDCl3) δ 8.04 (dt, J ) 1.9, 8.4 Hz, 2H), 7.61 (dt, J
) 1.8, 8.5 Hz, 2H), 7.52 (s, 1H), 3.91 (s, 3H). 13C NMR (100
MHz, CDCl3) δ 165.9, 139.0, 135.5, 129.4, 129.1, 127.8, 91.4,
51.7. Anal. Calcd for C10H8Br2O2: C, 37.54; H, 2.52. Found:
C, 37.74; H, 2.63.
Gen er a l P r oced u r e for th e P r ep a r a tion of Mon obr o-
m id es 2. A solution of a starting dibromide 1 (1.0 mmol), tris-
(dibenzylideneacetone)dipalladium(0) (Pd2dba3, 0.025 mmol),
tris(2-furyl)phosphine (TFP, 0.15 mmol), and a stannane (1.05
mmol) in toluene (5 mL) was flushed with nitrogen twice and
heated at 100 °C for 20 h. The reaction mixture was then
filtered through silica gel and rinsed with 20% ether in hexane.
The filtrate was concentrated and purified by column chro-
matography. The product could be further purified by recrys-
tallization from ethanol to give analytically pure samples.
Meth yl (Z)-4-(2-Br om o-2-p h en ylvin yl)ben zoa te (2a ): 1H
NMR (400 MHz, CDCl3) δ 8.04 (td, J ) 1.7, 8.5 Hz, 2H), 7.74
(d, J ) 8.3 Hz, 2H), 7.62 (m, 2H), 7.35 (m, 3H), 7.20 (s, 1H),
3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.6, 140.7, 140.5,
129.4, 129.3, 129.06, 129.03, 128.9, 128.3, 127.7, 126.2, 52.0.
Anal. Calcd for C16H13BrO2: C, 60.59; H, 4.13. Found: C, 60.69;
H, 4.28.
(4S)-2,2-Dim eth yl-4-[(E)-2-p h en yl-1,3-bu ta d ien yl]-1,3-
d ioxola n e (5d ): 1H NMR (400 MHz, CD3OD) δ 7.35-7.24 (m,
5H), 6.85 (ddd, J ) 0.8, 11.0, 17.4 Hz, 1H), 5.55 (d, J ) 8.5
Hz, 1H), 5.36 (td, J ) 1.8, 11.0 Hz, 1H), 5.10 (m, 2H), 4.17
(dd, J ) 6.4, 8.1 Hz, 1H), 3.63 (t, J ) 7.8 Hz, 1H), 1.41 (s, 3H),
1.40 (s, 3H); 13C NMR (100 MHz, CD3OD) δ 143.7, 140.0, 132.5,
127.9, 127.7, 127.1, 119.2, 109.0, 73.7, 72.3, 69.1, 25.6, 24.7.
Anal. Calcd for C15H18O2: C, 78.23; H, 7.88; Found: C, 78.25;
H, 7.98.
Ack n ow led gm en t. We thank Mr. Rodger Henry for
determining crystal structures of 2a and 5b. The
authors are grateful to Dr. Kenneth Barr for discussions
and suggestions.
Su p p or tin g In for m a tion Ava ila ble: Elemental analyses
and 1H NMR and 13C NMR spectral data for all the new
compounds (1c,i,k , 2b-j,l-p , 3a , 4b-d ,n -p , 5b,c,e-g),
information about the known compounds (1b,d -h ,j, 2k , 3k ,
4a ,e-m ), and X-ray structural data for 2a and 5b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Gen er a l P r oced u r e for th e P r ep a r a tion of Alk yn es 4.
A solution of a starting dibromide 1 (1.0 mmol), a stannane
(1.05 mmol), N,N-diisopropylethylamine (DIPEA, 1.50 mmol),
Pd2dba3 (0.025 mmol), and TFP or tris(4-methoxyphenyl)-
J O991116K