Palladium-catalyzed three-component 1:2:1 coupling of aryl iodides, alkynes, and alkenes to produce 1,3,5-hexatriene derivatives

Article abstract of DOI:10.1002/adsc.200900096

The intermolecular three-component coupling of aryl iodides, diarylacetylenes, and alkenes effectively proceeds in the presence of palladium acetylacetonate and silver acetate as catalyst and base, respectively, to give the corresponding 1:2:1 coupling pr

Full text of DOI:10.1002/adsc.200900096

UPDATES
DOI: 10.1002/adsc.200900096
Palladium-Catalyzed Three-Component 1:2:1 Coupling of Aryl
Iodides, Alkynes, and Alkenes to Produce 1,3,5-Hexatriene
Derivatives
Hakaru Horiguchi,a Koji Hirano,a Tetsuya Satoh,a,* and Masahiro Miuraa,*
a
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Fax : (+81)-6-6879-7362; phone: (+81)-6-6879-7361; e-mail: satoh@chem.eng.osaka-u.ac.jp or
miura@chem.eng.osaka-u.ac.jp
Received: February 11, 2009; Revised: April 20, 2009; Published online: June 2, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900096.
Abstract: The intermolecular three-component cou-
pling of aryl iodides, diarylacetylenes, and alkenes
effectively proceeds in the presence of palladium
acetylacetonate and silver acetate as catalyst and
base, respectively, to give the corresponding 1:2:1
coupling products, 1,3,5-hexatriene derivatives. A
further homologation of the oligoene chain of the
three-component coupling products by a simple
procedure is also presented.
lecular cyclization with alkynylACHTGNUTERNNU(G halo)arenes followed
by intermolecular termination or the reverse with
substrates such as alkenylhaloarenes and alkynes have
been studied extensively,[1,2] the fully intermolecular
version to afford p-conjugated acyclic compounds
have been less explored.[3–6] As one of the rare but ef-
ficient examples, Larock and co-workers reported the
1:1:1 coupling of aryl iodides, internal alkynes, and or-
ganoboron reagents (route a in Scheme 1).[3b–d] We
have also demonstrated that two molecules of alkynes
can be inserted between aryl halides and arylboronic
acids to produce the corresponding 1:2:1 coupling
products, 1,4-diaryl-1,3-butadienes.[5] In this unique
four-molecule coupling, the use of a silver(I) salt as
base was essential to achieve the double alkyne inser-
tion effectively.
À
Keywords: C C coupling; Heck reaction; multi-
component reactions; oligoenes; palladium
The palladium-catalyzed arylation of internal alkynes
As an example of route b in Scheme 1, on the other
with aryl halides or their synthetic equivalents via car- hand, we have developed a 1:1:1 coupling of aryl hal-
bometalation is a powerful tool for the construction ides, alkynes, and alkenes to produce 1,3-butadiene
of p-conjugated molecules.[1] Such reactions are often derivatives.[6] During the course of a further study of
carried out with the addition of various terminators this reaction, we observed that the double alkyne in-
including organometallic reagents, alkenes, and termi- sertion can also take place smoothly between aryl hal-
nal alkynes to give rise to three-component coupling ides and alkenes by employing the Pd/Ag catalyst
products (Scheme 1). While the reactions via intramo- system (Scheme 2).[5,7] The scope of the straightfor-
ward synthesis of oligoene derivatives, which are of
interest for their photo- and electrochemical and bio-
logical properties,[8] is described herein.
Scheme 1. Palladium-catalyzed three-component 1:1:1 cou-
pling of aryl halides, alkynes, and terminators.
Scheme 2. Palladium-catalyzed three-component coupling of
aryl halides, alkynes, and alkenes.
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Hakaru Horiguchi et al.
UPDATES
Table 1. Reaction of iodobenzene (1a) with diphenylacetylene (2a) and butyl acrylate
(3a).[a]
[a]
Reaction conditions: [1a]:[2a]:[3a]:
xylene (5 mL) under N2.
GC yield based on the amount of 1a used. Value in parenthesis indicates yield after
ACHUTGTNRNEUG[N Pd-cat.]:AHCTUNGTRNEN[UGN AgOAc]=1:4:1:0.05:2 (in mmol), in o-
[b]
purification.
(2E,4E):ACTHNUTRGNE(NUG 2E,4Z)=10:1.
With AgOAc (1 mmol).
With AgOAc (3 mmol).
2a (6 mmol) was used.
[c]
[d]
[e]
[f]
When iodobenzene (1a) was treated with diphen- The alkenes with an electron-withdrawing group such
ylacetylene (2a) (4 equiv.) and butyl acrylate (3a) as ethyl, isobutyl, and cyclohexyl acrylates and N,N-
(1 equiv.) in the presence of Pd(OAc)2 (5 mol%) and dimethylacrylamide smoothly reacted with 1a and 2a
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AgOAc (2 equiv.) in o-xylene at 1408C for 3 h, the to produce the corresponding trienes 4b–e (entries 1–
1:2:1 coupling proceeded predominantly to afford 4). Although these trienes were obtained as mixtures
butyl 4,5,6,7,7-pentaphenyl-2,4,6-heptatrienoate (4a) of geometrical isomers, each major (2E,4E)-isomer
in 29% yield, along with minor amounts of 1:1:1 and was found to be separable by recrystallization. The
1:2:0 coupling products, 5a[6a,b] and 6a,[7] respectively structure of (2E,4E)-4e was confirmed by X-ray crys-
(entry 1 in Table 1). Fortunately, the use of Pd
in place of Pd(OAc)2 as catalyst dramatically im- 4-Methoxystyrene also underwent the three-compo-
proved the yield of 4a up to 72% (entry 2, acac=ace- nent coupling with 1a and 2a to afford 6-(4-methoxy-
tylacetonate). The NMR spectra of isolated 4a indi- phenyl)-1,1,2,3,4-pentaphenyl-1,3,5-hexatriene (4f),
cated that it contained a minor amount of its geomet- albeit in a moderate yield (entry 5). The reactions of
rical isomer [(2E,4E):(2E,4Z)=ca. 10:1]. Both de- 4-iodotoluene with 2a and 3 gave a complex mixture
(acac)2 tal structure analysis (see Supporting Information).[9]
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
creasing and increasing the amount of AgOAc (en- of at least three geometrical isomers of the expected
tries 3 and 4) and the reaction temperature (entries 5 triene in 59% yield. Therefore, the reactions using the
and 6) somewhat decreased the product yield. The substrate combinations of aryl iodides and diarylace-
use of a further excess amount of 2a (6 equiv.) did not tylenes, in which same aryl groups are contained, with
improve the yield (entry 7).
3a were examined. Thus, from 4-methyl- and 4-
Table 2 summarizes the results for the reactions of chloro-substituted iodobenzenes and diphenylacety-
various aryl iodides, diarylacetylenes, and alkenes. lenes, the corresponding trienes 4g and 4h were ob-
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Palladium-Catalyzed Three-Component 1:2:1 Coupling
UPDATES
Table 2. Reaction of aryl iodides 1 with diarylacetylenes 2
and alkenes 3.[a]
than that with 2 even in the presence of AgOAc,
while the reason is not clear at the present stage.
We next examined the synthesis of higher oligoenes
by the present three-component coupling. Treatment
of b-bromostyrene (7) [(E):(Z)=6.5:1] with 2a
(4 equiv.) and 3a (1 equiv.) in the presence of
PdACTHNUTRGEN(NUG acac)2 (0.05 mmol) and AgOAc (2 mmol) in o-
xylene at 1408C for 1 h gave 1,2,3,4,6-pentaphenylful-
vene (8) in 55% yield as a 1:2:0 coupling product,[6b]
in place of expected acyclic tetraene derivatives
(Scheme 4). The intramolecular insertion of the al-
kenyl moiety of a trienylpalladium intermediate D,
formed by double alkyne insertion on a styrylpalladi-
um species C, may occur in preference to the inser-
tion of 3a.
Under similar conditions, 1-bromo-1,2,2-triphenyl-
AHCTUNGTREGeNNUN thene (9) underwent not the desired 1:2:1 but rather
1:1:1 coupling to afford triene 4a in 66% yield as a
single major product (Scheme 5). This reaction ap-
pears to involve a dienylpalladium intermediate F
formed by single alkyne insertion on an ethenylpalla-
dium species E. F may react with 3a rather than 2a in
a similar manner to that of B in Scheme 3.
Finally, the synthesis of a pentaene derivative was
achieved via the homologation of the oligoene chain
of the three-component coupling product.[6b] Thus, as
depicted in Scheme 6, trienyl bromide 10 was pre-
pared via hydrolysis and decarboxylative bromination
of (2E,4E)-4b.[12] As expected, 10 underwent the
second three-component coupling with 2a and 3a
[a]
Reaction conditions: [1]:[2]:[3]:[PdACHTNUGTRNENUG(acac)2]:ACHTUNGTRNE[NUGN AgOAc]=
1:4:1:0.05:2 (in mmol), in o-xylene (5 mL) at 1408C
under N2.
GC yield based on the amount of 1 used. Value in paren-
thesis indicates yield after purification.
At 1008C.
[b]
[c]
[d]
[e]
under previously reported conditions suitable for
[6b]
(3E,5E):
ACHTUNGTRENNUNG(3Z,5E)=80:20.
1:1:1 coupling using NaHCO3
to give butyl
A significant amount of 1:1:1 coupling product, butyl
(2E,4E,6E,8E)-4,5,8,9,10,11,11-heptaphenyl-2,4,6,8,10-
undecapentaenoate (11) in 51% yield. As a whole,
the 1:3:2 coupling of 1a, 2a, and 3a was achieved
(2E)-4,5,5-tris(4-chlorophenyl)-2,4-pentadienoate
(5b)
was also isolated (35%).
À
forming five C C bonds.
tained (entries 6 and 7). In contrast to the 1:1:1 cou-
pling we previously reported,[6b] the 1:2:1 coupling of
2-iodothiophene, bis(2-thienyl)acetylene, and 3a did
not take place at all.
Experimental Section
General Remarks
A plausible mechanism for the reaction of aryl io-
dides 1, diarylacetylenes 2, and alkenes 3 is illustrated
in Scheme 3. The formation of an arylpalladium inter-
mediate A via oxidative addition of 1 toward Pd(0)
species generated in situ followed by successive inser-
1H and 13C NMR spectra were recorded at 400 and
100 MHz, respectively, for CDCl3 solutions. MS data were
obtained by EI. GC analysis was carried out using a silicon
OV-17 column (i.d. 2.6 mmꢁ1.5 m) or a CBP-1 capillary
column (i.d. 0.5 mmꢁ25 m). GC-MS analysis was carried
tion of two alkyne molecules forms a dienylpalladium out using a CBP-1 capillary column (i.d. 0.25 mmꢁ25 m).
The structures of all products were unambiguously deter-
mined by 1H and 13C NMR with the aid of NOE, COSY,
HMQC, and HMBC experiments and X-ray crystal structure
analysis.
Bis(4-methylphenyl)acetylene, bis(4-chlorophenyl)acety-
lene, and bis(2-thienyl)acetylene were prepared according to
published procedures.[13] Other starting materials were com-
mercially available. Characterization data of all products are
reported in the Supporting Information. The following ex-
perimental procedures may be regarded as typical in meth-
intermediate B. Then, insertion of 3, b-hydrogen elim-
ination, and release of HX to regenerate Pd(0) may
occur to allow the catalytic production of trienes 4.
The results in Table 1 and Table 2 imply that E/Z iso-
merization takes place in the intermediate B.[10] The
use of AgOAc as base, in contrast to NaHCO3 which
brought about 1:1:1 coupling, seems to promote the
alkyne insertion steps by eliminating the iodide ligand
on A.[5,7] The lack of triple insertion[5a,11] of 2 suggests
that the reaction of B with 3 is significantly faster odology and scale.
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Hakaru Horiguchi et al.
UPDATES
Scheme 3. A plausible mechanism for the reaction of 1 with 2 and 3.
Scheme 4. Palladium-catalyzed coupling of b-bromostyrene (7) with 2a and 3a.
Scheme 5. Palladium-catalyzed coupling of 1-bromo-1,2,2-triphenylethene (9) with 2a and 3a.
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Palladium-Catalyzed Three-Component 1:2:1 Coupling
UPDATES
Acknowledgements
This work was partly supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan and the Sumitomo Foundation.
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ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
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