Stereodivergent synthesis of 2-alkynyl buta-1,3-dienes using Sonogashira coupling with controllable retention or inversion of olefin geometry

Article abstract of DOI:10.1016/j.tetlet.2019.151565

A stereodivergent approach to 2-alkynyl buta-1,3-dienes from a single stereoisomer of starting α-bromoenal has been developed. By simply switching the sequence of Sonogashira and Horner-Wadsworth-Emmons reactions, it is possible to obtain these branched d

Full text of DOI:10.1016/j.tetlet.2019.151565

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Stereodivergent synthesis of 2-alkynyl buta-1,3-dienes using Sonogashira cou-
pling with controllable retention or inversion of olefin geometry
Rinat N. Shakhmaev, Maria G. Ignatishina, Vladimir V. Zorin
PII:
S0040-4039(19)31364-4
DOI:
https://doi.org/10.1016/j.tetlet.2019.151565
TETL 151565
Reference:
Tetrahedron Letters
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Revised Date:
Accepted Date:
23 August 2019
19 December 2019
23 December 2019
Please cite this article as: Shakhmaev, R.N., Ignatishina, M.G., Zorin, V.V., Stereodivergent synthesis of 2-alkynyl
buta-1,3-dienes using Sonogashira coupling with controllable retention or inversion of olefin geometry, Tetrahedron
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Stereodivergent synthesis of 2-alkynyl buta-
1,3-dienes using Sonogashira coupling with
controllable retention or inversion of olefin
geometry
Leave this area blank for abstract info.
Rinat N. Shakhmaev*, Maria G. Ignatishina, Vladimir V. Zorin
R1
One-pot
O
O
O
1) Sonogashira
coupling
1) HWE olefination
O
O
Br
R1
R1
2) Sonogashira
coupling
2) HWE olefination
R2
R2
up to 98 % 2E,4E
100 % 2E,4Z

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Stereodivergent synthesis of 2-alkynyl buta-1,3-dienes using Sonogashira coupling
with controllable retention or inversion of olefin geometry
Rinat N. Shakhmaev*, Maria G. Ignatishina, Vladimir V. Zorin
Faculty of Technology, Ufa State Petroleum Technological University, Ufa 450062, Bashkortostan, Russia
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A stereodivergent approach to 2-alkynyl buta-1,3-dienes from a single stereoisomer of starting
α-bromoenal has been developed. By simply switching the sequence of Sonogashira and Horner-
Wadsworth-Emmons reactions, it is possible to obtain these branched dienynes with retention or
almost complete inversion of the double bond configuration.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Sonogashira coupling
2-Alkynyl buta-1,3-dienes
Vinyl halides
Stereodivergent synthesis
The Pd/Cu-catalyzed cross-coupling of vinyl halides or
pseudohalides with terminal alkynes (Sonogashira reaction) is the
most straightforward and reliable method for the preparation of
isomerically pure conjugated enynes. The high efficiency, mild
reaction conditions and operational simplicity of this reaction
have contributed to the rapid development of the chemistry of
simple enynes and enediyne anticancer antibiotics, but there are
only a few examples of its use for the synthesis of branched
unsaturated compounds.1
dien-1-yl]benzene with trimethylsilylacetylene,4b as well as the
reactions of 4-alkynyl-substituted 2-iodo-1,3-butadienes and
(2Z,4E)-3-iodo-5-(trimethylsilyl)penta-2,4-dienoic
acid
derivatives with a number of terminal alkynes.11 It was reported
that these reactions proceed with retention of configuration, as
expected for Sonogashira reaction. However, for cross-coupling
reactions of 2-halo-1,3-butadienes, which have an extended π-
system and are simultaneously vinylic and allylic, retention of
configuration is not obligatory. Experience has shown that a
cross-coupling involving 2-halo-1,3-butadienes can lead to an
unexpected stereochemical result. The most well-known example
is the Pd-catalyzed Negishi cross-coupling of 2-bromo-1,3-
butadienes with various organozinc compounds, proceeding with
retention or clean stereoinversion of the Br-bearing C=C bond
depending on the type of ligand used.12 Here, we report on the
synthesis of novel 2-alkynyl-1,3-butadienes via Sonogashira
coupling with retention and unusual inversion of the double bond
configuration.
One of the interesting and little-known classes of enynes are
2-alkynyl buta-1,3-dienes, which are useful diene components in
Diels-Alder reactions2 and key structural motifs of advanced π-
conjugated polymers and chromophores.3 There are several
examples of the synthesis of these compounds based on Pd-
catalyzed alkenylation of 2-bromo(triflato)-1,3-enynes.4 The
formation of branched dienyne skeleton by the reaction of some
thiophosphates with sodium acetylides was reported.5 Shi
synthesized a series of 2-alkynyl buta-1,3-dienes by the reaction
of 1,1-disubstituted 2,4-diiodobut-1-enes with alkynes in the
presence of Pd(PPh3)4/CuI catalytic system or only CuI.6 The
Pd(PPh3)4-catalyzed decarboxylation of buta-2,3-dienyl 2'-
alkynoates allows the rapid construction of 2-alkynyl buta-1,3-
dienes.7 The formation of these compounds by Ru-catalyzed
cross-metathesis of 1,3-diynes with 1-octene has also been
described.8 More recently, the approach to 2-alkynyl buta-1,3-
dienes based on Rh-catalyzed homocoupling reaction of γ-
alkylated tert-propargylic alcohols has been developed.9
First, we developed an efficient method for the synthesis of
these compounds using
a one-pot sequence Sonogashira
coupling/Horner-Wadsworth-Emmons (HWE) olefination. The
Pd/Cu-catalyzed cross-coupling of (2Z)-2-bromo-3-phenylprop-
2-enal 1a with oct-1-yne smoothly proceeded in the presence of
PdCl2(PPh3)2, CuI and diisopropylamine in MeCN to give the
corresponding enyne aldehyde. Its in situ olefination with triethyl
phosphonoacetate in the presence of LiCl (Masamune-Roush
conditions) proved to be optimal for the efficient formation of
dienyne 2aa (Table 1). The choice of diisopropylamine and
MeCN as common base and solvent is key to the success of the
one-pot reaction. The organic bases commonly used in the
Masamune-Roush olefination (DBU, DIPEA13 and Et3N14) gave
There are very few examples of the synthesis of 2-alkynyl
buta-1,3-dienes by Sonogashira cross-coupling of 2-halo-1,3-
butadienes with alkynes. These include the reactions of 6-
hydroxy(bromo)-substituted (3Z)-2-iodohexa-1,3-dienes with
phenylacetylene,10 the reaction of [(3Z,5E)-4-bromodeca-3,5-

2
Tetrahedron
an unsatisfactory result, and less polar solvents (e.g., THF or
A number of alkynes bearing various functional groups were
toluene) retarded the olefination.
investigated in this one-pot sequence. In all cases, the
corresponding dienynes were obtained as pure (2E,4Z)-isomers
2ba-2ga with good yields (63-86%), with the exception of
dienyne 2ha (yield 22%) obtained from N,N-dimethylprop-2-yn-
1-amine (Table 1). (2Z)-2-Bromo-3-arylprop-2-enals bearing
both electron-donating (OMe, 1b) and electron-withdrawing
(NO2, 1c) groups at the para position of the phenyl ring were
tolerated and gave the corresponding products 2ia, 2ja in 63-67%
yields.
Table 1. Synthesis of 2-alkynyl buta-1,3-dienes by a one-pot
sequence Sonogashira coupling/HWE olefinationa,b
R2
1)
O
O
Pd(PPh3)2Cl2, CuI,
i-Pr2NH, MeCN, rt, 5 h
O
Br
R1
R1
2) (EtO)2P(O)CH2CO2Et,
LiCl, rt, 16 h
R2
1
2
O
O
O
Next, the possibility of synthesizing 2-alkynyl buta-1,3-dienes
from the same starting materials using the reverse sequence HWE
olefination/Sonogashira coupling was investigated. HWE
reaction of aldehyde 1a with triethyl phosphonoacetate under
standard Masamune-Roush conditions (DBU, LiCl) provided
(2E,4Z)-4-bromo-5-phenylpenta-2,4-dienoate 3a in high yield
(85%) and complete E-stereoselectivity. The Sonogashira
coupling of 3a with oct-1-yne in the presence of PdCl2(PPh3)2,
CuI and diisopropylamine in MeCN was not stereospecific and
gave a mixture of isomers with a slight predominance of the
inversion product (2E,4Z/2E,4E = 44:56) (Table 2). The 4E
geometry was established on the basis of NOESY correlation
between H-3 and the ortho-aromatic proton, as well as the lack of
correlation between H-3 and the benzylidene proton (Figure 1).
O
O
O
O
O
C6H13
C9H19
2ca, 86%
2aa, 78%
2ba
, 81%
O
O
O
O
O
OH
Si
OH
2da, 79%
2ea, 63%
2fa
, 68%
O
O
O
O
O
Table 2. Optimization of Sonogashira coupling of 2-bromo-
1,3-butadiene 3a with oct-1-ynea
MeO
C6H13
2ia, 67%
N
2ha, 22%
2ga, 65%
O
O
C6H13
O
O
O
Br
3a
Pd-catalyst, ligand, CuI,
O
i-Pr2NH
2ab
O2N
C6H13
C6H13
entry
catalyst
ligand
solvent time,
h
E,Z/E,Eb
yieldc
(%)
2ja, 63%
aReaction conditions: 1 (0.71 mmol), alkyne (0.85 mmol), Pd(PPh3)2Cl2 (5
mol %), CuI (10 mol %), i-Pr2NH (2.84 mmol) in MeCN (2 ml) under argon
at rt for 5 h, then (EtO)2P(O)CH2CO2Et (1.07 mmol), LiCl (1.07 mmol) at rt
for16 h. bIsolated yield by column chromatography.
1
2
3
4
5
6
7
8
Pd(PPh3)2Cl2
Pd(OAc)2
-
MeCN
MeCN
MeCN
MeCN
THF
5
24
48
24
24
5
44:56
15:85
32:68
-
87
80
85
6
P(o-Tol)3
Pd(OAc)2
XPhos
Pd(OAc)2
BINAP
The one-pot reaction proceeded with complete E-
stereoselectivity of the newly formed C=C bond and expected
retention of configuration of the Br-bearing double bond to
produce single (2E,4Z)-isomer, as confirmed by NMR
spectroscopy. The 2E configuration was established on the basis
of the large coupling constant (J = 15.2 Hz) of the vinylic
protons. The 4Z geometry was determined on the basis of
NOESY correlation between H-3 and the benzylidene proton, as
well as the lack of correlation between H-3 and the ortho-
aromatic proton (Figure 1). It is interesting to note that carrying
out this one-pot reaction with a mixture of isomers of 1a (Z/E =
55:45) led to a similar stereochemical result. It is unclear,
however, whether the fast inversion of thermodynamically
unstable (E)-1a isomer15 occurs under the reaction conditions, or
isomerization takes place within the Sonogashira catalytic cycle.
Pd(PPh3)2Cl2
-
-
-
-
79:21
4:96
4:96
6:94
72
80
63
72
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
DMA
DMAd
DMF
5
5
aReaction conditions: 3a (0.36 mmol), oct-1-yne (0.43 mmol), Pd-catalyst (5
mol %), ligand (10 mol %), CuI (10 mol %), i-Pr2NH (1.08 mmol) in a
specific solvent (2 mL) under argon at rt. Determined by H NMR analysis
of the crude reaction mixture. cIsolated yield of 2ab as a mixture of 2E,4Z and
2E,4E isomers by column chromatography. (d) 40 oC.
b
1
Assuming that the driving force of the isomerization is steric
crowding created by the proximity of phenyl group and
phosphine-ligated palladium moiety in the oxidative addition
complex (or subsequent species of the catalytic cycle), we tested
several bulky ligands in this reaction. The monophosphines with
large cone angles such as P(o-Tol)3 or XPhos promoted the
preferential formation of the inversion product (2E,4E)-2ab and
unfortunately significantly reduced the rate of the cross-coupling
reaction. However, subsequent investigation of the solvent effect
revealed that the degree of Z/E isomerization strongly depends on
the polarity of the solvent. The (2E,4Z)-isomer was the main
reaction product when using THF as solvent, whereas in more
polar solvents such as DMA nearly complete inversion was
observed with formation of (2E,4E)-isomer (Table 2). Thus, by
simply switching the sequence of Sonogashira and Horner-
Wadsworth-Emmons reactions, it is possible to obtain 2-alkynyl
H
H
O
H
O
O
H
O
C6H13
C6H13
(2E,4Z)-2aa
(2E,4E)-2ab
Figure 1. Assignment of dienyne configuration by NOESY correlations

3
buta-1,3-dienes with retention or almost complete inversion of
the double bond configuration. To our best knowledge, this is the
first example of the preparation of both individual E and Z enyne
isomers from a single stereoisomer of vinyl electrophiles using
Sonogashira reaction. It should be noted that significant reverse
isomerization of the (2E,4E)-isomer into the (2E,4Z)-isomer was
observed during the purification by column chromatography on
silica gel, neutral alumina or even deactivated silica gel.
Therefore, we had to determine the 2E,4Z/2E,4E ratio of the
inversion (88-98% 2E,4E) affording the corresponding
dienynes 2bb-2hb in good yields (64-82%), including the
reaction with challenging N,N-dimethylprop-2-in-1-amine (Table
3). The cross-coupling of electron-rich ethyl (2E,4Z)-4-bromo-5-
(4-methoxyphenyl)penta-2,4-dienoate 3b with oct-1-yne to form
dienyne 2ib was somewhat faster than that of either unsubstituted
3a or electron-poor nitro-substituted bromodiene 3c. This is the
opposite of the general reactivity trend of substituted aryl
electrophiles in the Sonogashira coupling.1a It is also interesting
that the stereoselectivity of the formation of methoxy-substituted
dienyne 2ib was as high as that of unsubstituted 2ab (95 %
2E,4E), while in the case of nitro-substituted dienyne 2jb it was
significantly lower (83% 2E,4E) (Table 3).
1
crude 2ab by H NMR spectroscopy and the isolated yield (as a
mixture of 2E,4Z and 2E,4E isomers) by column chromatography
(see Supporting Information).
Table 3. Synthesis 2-alkynyl buta-1,3-dienes by Sonogashira
coupling of 2-bromo-1,3-butadiene 3 with alkynesa,b,c
Next, we tested the effect of the conjugated carbonyl group,
which is believed to contribute to the isomerization of the C=C
bond through resonance.16 The sequence including Sonogashira
coupling of (2Z)-2-bromo-3-phenylprop-2-enal 1a with 3,3-
dimethyl-1-butyn and subsequent Wittig reaction of the resulting
enyne aldehyde with methylenetriphenylphosphorane gave
dienyne 2ka as a single (Z)-isomer in low overall yield. The
reverse sequence Wittig reaction/Sonogashira coupling led to the
predominant (although not so impressive) formation of the
inversion product 2kb (E/Z = 82:18) (Scheme 1). Thus, a key
requirement for the inversion in the Sonogashira coupling is the
presence of a C=C bond conjugated with the Br-bearing C=C
bond. This is consistent with the observed stereochemistry in the
Negishi cross-coupling of 2-bromo-1,3-butadienes.12
1
(EtO)2P(O)CH2CO2Et,
DBU, LiCl, MeCN,
R1
rt, 5 h
O
O
R2
O
O
Br
R1
Pd(PPh3)2Cl2, CuI, i-Pr2NH,
DMA, rt, 5 h
3
2
R2
O
O
O
O
O
O
C6H13
C9H11
1)
2ab, 80%, 96% 2E,4E
2cb
, 80%, 97% 2E,4E
2bb, 82%, 95 % 2E,4E
Pd(PPh3)2Cl2, CuI
i-Pr2NH, MeCN,
1) Ph3P=CH2,THF,
0 oC to rt, 1 h
O
rt, 3 h
85%
35%
Br
2)
2) Ph3P=CH2,THF,
O
O
O
O
O
O
0 oC to rt, 24 h
24%
1a
Pd(PPh3)2Cl2, CuI
i-Pr2NH, DMA,
rt, 5 h
2kb, 82 % E
2ka, 100 % Z
77%
OH
OH
Si
Scheme 1. Switching the sequence of Sonogashira and Wittig reactions
Finally, some aspects of the isomerization mechanism were
considered. It is clear that the inversion occurs along the
Sonogashira catalytic cycle, since no significant isomerization
was observed during prolonged stirring of 2-bromo-1,3-butadiene
3a or dienyne 2aa in MeCN in the presence of all reagents
[Pd(PPh3)2Cl2, CuI, diisopropylamine] except the alkyne. The
Z/E isomerization in cross-coupling reactions of simple vinyl
halides has been reported in several studies. The ligand-
dependent isomerization mechanisms within the cross-coupling
catalytic cycle have been proposed for the loss of stereochemistry
in Suzuki-Miyaura,17 Stille18 and Negishi19 reactions. More
recently, the extensive isomerization in Suzuki cross-couplings of
2fb, 70%, 96% 2E,4E
2db, 74%, 92% 2E,4E
2eb, 70%, 98% 2E,4E
OMe
O
O
O
O
O
O
N
C6H13
2ib, 64%, 95% 2E,4Ed
2gb, 67%, 88% 2E,4E
2hb, 64%, 95% 2E,4E
NO2
haloenones was explained by
isomerization process.20 However, for 2-halo-1,3-butadienes,
bearing halogen at the vinylic and allylic position
a
separate Pd-catalyzed
O
O
a
simultaneously and thus capable of both vinylic and allylic type
Pd-catalyzed transformations, the isomerization mechanism may
be even more complicated. The observed stereoinversion may be
due to the relative thermodynamic stabilities of various possible
alkylidene-π-allylpalladium species.12a Similar complexes were
isolated and characterized by NMR spectroscopy and X-ray
crystallography.21 However, the inversion mechanism involving
such intermediates should be different from the widely accepted
π-σ-π rearrangement of simple allylpalladium derivatives, which
requires a double Z/E stereoinversion (Scheme 2).
C6H13
2jb, 49%, 83% 2E,4Ee
aReaction conditions: 3 (0.36 mmol), alkyne (0.43 mmol), Pd(PPh3)2Cl2 (5
mol %), CuI (10 mol %), i-Pr2NH (1.08 mmol) in DMA (2 ml) under argon at
rt for 5 h. b2E,4Z/2E,4E ratio of the crude 2 by 1H NMR spectroscopy.
cIsolated yield (as a mixture of 2E,4Z and 2E,4E isomers) by column
chromatography. dReaction time was 2 h. Reaction time was 6 h.
e
Using DMA as a solvent, the same series of functionalized
alkynes were allowed to react with bromodiene 3a. In all cases,
the Sonogashira couplings proceeded with almost complete

4
Tetrahedron
COOEt
COOEt
References and notes
H
Ar
Ar
PdLnX
H
XLnPd
1. (a) Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979-2017. (b)
Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834-871. (c)
Chinchilla, R.; Nájera, C. Chem. Rev. 2007, 107, 874-922. (d) Chinchilla,
R.; Nájera, C. Chem. Soc. Rev. 2011, 40, 5084-5121. (e) Wang, D.; Gao,
S. Org. Chem. Front. 2014, 1, 556-566. (f) Chinchilla, R.; Nájera, C.
Chem. Rev. 2014, 114, 1783-1826. (g) Zhou,Y.; Zhang, Y.; Wang, J.
Org. Biomol. Chem. 2016, 14, 6638-6650.
2E,4Z
COOEt
•
XLnPd
H
H
Ar
Ar
2. Hopf, H.; Jäger, H.; Ernst, L. Liebigs Ann. Chem. 1996, 815-824.
3. (a) Pahadi, N. K.; Camacho, D. H.; Nakamura, I.; Yamamoto, Y. J. Org.
Chem. 2006, 71, 1152-1155. (b) Michinobu, T.; Boudon, C.;
Gisselbrecht, J.-P.; Seiler, P.; Frank, B.; Moonen, N. N. P.; Gross, M.;
Diederich, F. Chem. Eur. J. 2006, 12, 1889-1905. (c) McQuade, D. T.;
Pullen, A. E.; Swager, T. M. Chem. Rev. 2000, 100, 2537-2574. (d) Tour,
J. M. Acc. Chem. Res. 2000, 33, 791-804. (e) Michinobu, T.; May, J. C.;
Lim, J. H.; Boudon, C.; Gisselbrecht, J.-P.; Seiler, P.; Gross, M.;
Biaggio, I.; Diederich, F. Chem. Commun. 2005, 737-739.
4. (a) Karabelas, K.; Hallberg, A. J. Org. Chem. 1988, 53, 4909-4914. (b)
Uenishi, J.; Matsui, K. Tetrahedron Lett. 2001, 42, 4353-4355. (c)
Uenishi, J.; Matsui, K.; Ohmi, M. Tetrahedron Lett. 2005, 46, 225-228.
5. Maciągiewicz, I.; Dybowski, P.; Skowrońska, A. J. Organomet. Chem.
2002, 643-644, 501-503.
6. (a) Shao, L.-X.; Shi, M. J. Org. Chem. 2005, 70, 8635-8637. (b) Shao,
L.-X.; Shi, M. Tetrahedron 2007, 63, 11938-11942.
7. Sim, S. O.; Park, H.-J.; Lee, S. I.; Chung, Y. K. Org. Lett. 2008, 10, 433-
436.
8. Kim, M.; Miller, R. L.; Lee, D. J. Am. Chem. Soc. 2005, 127, 12818-
12819.
9. Dou, X.; Liu, N.; Yao, J.; Lu, T. Org. Lett. 2018, 20, 272-275.
10. (a) Yu, L.; Meng, B.; Huang, X. J. Org. Chem. 2008, 73, 6895-6898. (b)
Meng, B.; Yu, L.; Huang, X. Tetrahedron Lett. 2009, 50, 1947-1950.
11. (a) Bujard, M.; Ferri, F.; Alami, M. Tetrahedron Lett. 1998, 39, 4243-
4246. (b) Fiandanese, V.; Babudri, F.; Marchese, G.; Punzi, A.
Tetrahedron 2002, 58, 9547-9552.
12. (a) Zeng, X.; Hu, Q.; Qian, M.; Negishi, E. J. Am. Chem. Soc. 2003, 125,
13636-13637. (b) Zeng, X.; Qian, M.; Hu, Q.; Negishi, E. Angew. Chem.,
Int. Ed. 2004, 43, 2259-2263.
13. Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.; Masamune,
S.; Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25, 2183-2186.
14. Rathke, M. W.; Nowak, M. J. Org. Chem. 1985, 50, 2624-2626.
15. The E/Z mixture of 2-bromo-3-phenylprop-2-enal resulting from
bromination/dehydrobromination of cinnamaldehyde is completely
converted to the Z-isomer after 4 days at room temperature. See also:
Gilley, C. B.; Buller, M. J.; Kobayashi, Y. Org. Lett. 2007, 9, 3631-
3634.
XLnPd
H
H
Ar
XLnPd
COOEt
2Z,4E
COOEt
Scheme 2. Double Z/E stereoinversion via π-σ-π rearrangement
The loss of Z geometry may occur via a zwitterionic
palladium carbene species (with either an anionic or cationic
benzylic carbon), which can be considered as real intermediates
or resonance structures (Scheme 3). Such dipolar intermediates
were first proposed to explain the isomerization of cis-
vinylrhodium complexes.22 Later, this mechanism was used to
explain the stereochemistry of formal anti-carbopalladation16b,23
and other metallocatalyzed additions to alkynes,24 as well as
cross-coupling reactions involving simple vinyl electrophiles.17-19
From the steric point of view, the trans relationship between the
aryl group and the bulky phosphine-ligated Pd moiety should be
thermodynamically more favorable than the initial
Z
configuration. This mechanism is partly supported by the
beneficial effect of polar solvents such as DMA capable of
stabilizing zwitterionic intermediates on the formation of the
inversion product. The rapid conversion of methoxy-substituted
bromodiene 3b and anomalously low stereoselectivity of the
formation of nitro-substituted dienyne 2jb are also in agreement
with the positive charge buildup on the benzylic carbon. Other
isomerization
mechanisms
via
η2-vinylpalladium
or
metallacyclopropene species are also possible.24b,25
O
O
OEt
or
OEt
PdLnX
PdLnX
R
R
16. (a) Blackmore, T.; Bruce, M. I.; Stone, F. G. A. J. Chem. Soc., Dalton
Trans. 1974, 106-112. (b) Amatore, C.; Bensalem, S.; Ghalem, S.;
Jutand, A. J. Organomet. Chem. 2004, 689, 4642-4646.
Scheme 3. Isomerization via a zwitterionic palladium carbene species
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In summary, we have developed an efficient method for the
stereodivergent synthesis of 2-alkynyl buta-1,3-dienes using
Sonogashira and Horner-Wadsworth-Emmons reactions. By
simply switching the sequence of these reactions, it is possible to
obtain 2-alkynyl buta-1,3-dienes with retention or almost
complete inversion of the double bond configuration. This
approach to the control of stereochemistry could be useful in
stereoselective synthesis of branched enynes, especially when
only a single isomer of starting vinyl halides (pseudohalides) is
available.
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This work was supported by the Ministry of Science and
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Supplementary data
Supplementary data associated with this article can be found,
in the online version, at:
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Highlights
 Stereodivergent synthesis of branched dienynes
 Preparation of both individual E and Z enyne
isomers using Sonogashira coupling
 Almost complete inversion in Sonogashira
coupling
 High isomeric purity