Isomerization of electron-poor alkynes to the corresponding (E, E)-1,3-dienes using a bifunctional polymeric catalyst bearing triphenylphosphine and phenol groups

Article abstract of DOI:10.1055/s-0030-1258576

The use of a bifunctional non-cross-linked polystyrene bearing both phosphine and phenol groups for the organocatalytic isomerization of alkynes bearing electron-withdrawing ester substituents to afford the corresponding (E,E)-dienes in excellent yield an

Full text of DOI:10.1055/s-0030-1258576

LETTER
2617
Isomerization of Electron-Poor Alkynes to the Corresponding (E,E)-1,3-
Dienes Using a Bifunctional Polymeric Catalyst Bearing Triphenylphosphine
and Phenol Groups
Isomerization of
a
t
or
A
lk
h
yne
s
to the
C
y
orresponding (
E
,
E
K
)-1,3-Dienes ar-Wing Kwong, Michael Yunyi Fu, Henry Chun-Hin Law, Patrick H. Toy*
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China
Fax +85228571586; E-mail: phtoy@hku.hk
Received 28 July 2010
functional non-cross-linked polystyrene bearing both
Abstract: The use of a bifunctional non-cross-linked polystyrene
bearing both phosphine and phenol groups for the organocatalytic
isomerization of alkynes bearing electron-withdrawing ester sub-
stituents to afford the corresponding (E,E)-dienes in excellent yield
phosphine and phenol groups (1, Scheme 2) and its use as
a catalyst in a variety of Morita–Baylis–Hillman reac-
tions.9 Herein we describe the use of 1 to catalyze the
and stereoselectivity is described. When polystyrene functionalized isomerization of a wide range of ester-activated alkynes to
with only phosphine groups was used as the catalyst, either low or
no yield of the desired product was obtained. Thus both of the func-
the corresponding (E,E)-dienes in reactions where the de-
sired product is obtained after filtration through silica gel
tional groups of the bifunctional polystyrene catalyst were essential
and solvent removal.10
for efficient catalysis to occur. This bifunctional polymeric catalyst
Catalyst 1 was prepared according to our previously re-
ported procedure (Scheme 2).9 For the sake of compari-
son, we also prepared the corresponding monofunctional
polymer 2,8a which possesses only phosphine groups, by a
similar method. Since both of these polymers are non-
cross-linked, they are soluble in many organic solvents,
and can thus act as homogeneous catalysts. Their solubil-
ity allowed them to be analyzed by 31P NMR in order to
confirm the oxidation state of the phosphine groups to be
as depicted in Scheme 2. Furthermore, their loading levels
were found to be 1.0 and 1.2 mmol Ph3P g–1, respectively,
by elemental analysis.10
was also used to synthesize (E,E,E)-trienes and (E,E)-diene-substi-
tuted 2(H)-pyran-2-ones from the corresponding alkynes.
Key words: organocatalysis, polymer-supported catalyst, alkyne
isomerization, dienes, triphenylphosphine, phenol
In the early 1990s, the research groups of Trost1 and Lu2
reported Ph3P-catalyzed isomerization of alkynones to the
corresponding (E,E)-dienones. Subsequently, Rych-
novsky and Kim reported that the use of PhOH as a co-cat-
alyst allowed less activated alkynoates to be similarly
isomerized (Scheme 1),3 and this advancement has led
such isomerization reactions to be used in a variety of or-
ganic contexts,4 especially natural product synthesis.5
While such reactions are generally high yielding and ste-
reoselective, they suffer from the drawback that even
though Ph3P and PhOH act as catalysts, 0.5–1.0 equiva-
lents of each is generally used for the sake of efficiency.
Thus, purification of the desired compound can be tedious
and time consuming. Jiang and co-workers have tried to
address this issue by using heterogeneous polystyrene-
supported Ph3P as the catalyst in these reactions, but since
no PhOH was present, only alkynones were isomerized.6
As we wanted to extend upon the work of Jiang and see if
1 was capable of catalyzing the isomerization of
alkynoates, alkynes 3a–d were treated sequentially with
n-BuLi and then either ethyl chloroformate or benzyl
chloroformate in a one-pot procedure to afford alkynoates
4a–h (Scheme 3).11
With the desired substrates in hand, we compared their
isomerization using 1.0 equivalent of either 1 or 2 (1 M
benzene, 55 °C, 18 h) in parallel reactions. As can be seen
from Table 1, in all cases the use of 1 as the catalyst led to
excellent yield of the expected corresponding (E,E)-di-
enoate 5a–h, and the use of 2 as the catalyst resulted in ei-
ther low yield or no product formation. These
observations confirm that the presence of phenol is a re-
quirement for the efficient phosphine-catalyzed isomer-
ization of alkynoates, and that 1 is a viable alternative to
the catalyst combination of Ph3P and PhOH. For the reac-
tions catalyzed by 2 in which the isomerized product was
formed (entries 1, 2, 7, and 8), silica gel chromatography
was required to separate the unreacted starting material
from the product in order to determine the yield. Howev-
er, when 1 was used as the catalyst, the desired product
was obtained in pure form after filtration through silica
gel and solvent removal. Furthermore, in these reactions
the identity of the ester group does not seem to influence
O
O
Ph3P (1.0 equiv)
PhOH (1.0 equiv)
OR2
R1
OR2
R1
Scheme 1 Alkyne isomerization reactions catalyzed by Ph3P and
PhOH
We have studied polymer supports for organic chemistry,7
especially those functionalized with phosphine groups,8
and have recently reported the synthesis and use of a bi-
SYNLETT 2010, No. 17, pp 2617–2620
x
x
.x
x
.2
0
1
0
Advanced online publication: 23.09.2010
DOI: 10.1055/s-0030-1258576; Art ID: W12110ST
© Georg Thieme Verlag Stuttgart · New York

2618
C. K.-W. Kwong et al.
LETTER
1
1
5
1. AIBN, PhMe, 85 °C
2. TBAF, THF, r.t.
+
+
PPh2
OTBS
OH
PPh2
1
1
5
AIBN, PhMe, 85 °C
+
PPh2
PPh2
2
Scheme 2 Synthesis of phosphine functionalized polystyrenes
O
Table 1 Isomerization of 4a–h Using 1 and 2
1. n-BuLi, THF, –78 °C
OR3
O
R1
2. ClC(O)OR3, r.t.
R1
O
R2
R2
OR3
1 or 2
R1
OR3
R1
3a: R1 = n-Bu, R2 = H
3b: R1 = CH2OTBS, R2 = H
3c: R1 = Ph, R2 = H
4a: R1 = n-Bu, R2 = H, R3 = Et
4b: R1 = n-Bu, R2 = H, R3 = Bn
4c: R1 = CH2OTBS, R2 = H, R3 = Et
4d: R1 = CH2OTBS, R2 = H, R3 = Bn
4e: R1 = Ph, R2 = H, R3 = Et
4f: R1 = Ph, R2 = H, R3 = Bn
4g: R1–R2 = (CH2)4, R3 = Et
4h: R1–R2 = (CH2)4, R3 = Bn
R2
R2
5a–h
4a–h
3d: R1–R2 = (CH2)4
Entry Substrate Product
YieldusingYieldusing
1 (%)a
2 (%)a
O
1
2
3
4
5
6
4a
4b
4c
4d
4e
4f
84
28
Scheme 3 Synthesis of alkynoate isomerization substrates
n-Bu
OEt
5a
O
the efficiency of the reactions (entries 1, 3, 5, and 7 vs. 2,
4, 6, and 8).
91
90
89
90
85
40
0
n-Bu
OBn
5b
Having confirmed that 1 is a good catalyst for the isomer-
ization of alkynoates, we wanted to see if we could also
use it to synthesize (E,E,E)-trienoates. Thus, alkynes were
used as starting materials again to synthesize the required
isomerization substrates, and 3a–c were treated sequen-
tially with n-BuLi and DMF to afford the corresponding
aldehydes 6a–c. These were purified and then reacted
with (carboethoxymethylene)triphenylphosphorane to af-
ford substrates 7a–c (Scheme 4).11
O
TBSO
OEt
5c
O
0
TBSO
OBn
5d
O
O
0
Ph
OEt
CHO
1. n-BuLi, THF, –78 °C
2. DMF, r.t.
5e
3a–c
R
0
6a: R = n-Bu
6b: R = CH2OTBS
6c: R = Ph
Ph
OBn
5f
O
O
O
OEt
7
8
4g
4h
84
92
53
49
Ph3P=CHCO2Et
CH2Cl2, r.t.
OEt
R
5g
7a: R = n-Bu
7b: R = CH2OTBS
7c: R = Ph
OBn
Scheme 4 Synthesis of alkynenoate isomerization substrates
5h
a Conditions: 4a–h (1.0 mmol), 1 or 2 (1.0 equiv), benzene (1.0 M),
55 °C, 18 h.
Gratifyingly when 7a–c were subjected to isomerization
with catalyst 1 using conditions similar for the isomeriza-
tion of 4a–h to 5a–h, good yield of the expected corre-
Synlett 2010, No. 17, 2617–2620 © Thieme Stuttgart · New York

LETTER
Isomerization of Electron-Poor Alkynes to the Corresponding (E,E)-1,3-Dienes
2619
sponding (E,E,E)-trienoate 8a–c was obtained in all cases synthesis of related biologically interesting natural prod-
(Table 2). However, when 2 was used as the catalyst, no ucts, and 1 is a suitable catalyst to study in such applica-
desired isomerized product was observed in any of the re- tions.
actions, even after prolonged reaction times. This seems
to indicate that the isomerization of 7a–c is more depen-
Table 3 Isomerization of 9a–c Using 1
dant upon the presence of phenol groups than are
alkynoates 4a–h.
1
9a–c
10a–c
Substrate
Product
Yield (%)a
100
Table 2 Isomerization of 7a–c Using 1
O
O
O
O
9a
9b
OEt
1
R
OEt
R
7a–c
8a–c
10a
Substrate
Product
Yield (%)a
72
O
83
89
O
O
7a
7b
7c
n-Bu
OEt
10b
8a
O
O
76
87
O
TBSO
OEt
9c
8b
O
10c
Ph
OEt
a Conditions: 9a–c (1.0 mmol), 1 (1.0 equiv), benzene (1.0 M), 55 °C,
8c
a Conditions: 7a–c (1.0 mmol), 1 (1.0 equiv), benzene (1.0 M), 55 °C,
18 h.
18 h.
In summary, we have found that a bifunctional polysty-
rene functionalized with both phosphine and phenol
groups (1) is capable of catalyzing the isomerization of a
wide range of ester-activated alkynes to the corresponding
(E,E)-dienes in high yield and stereoselectivity. Because
1 possesses both of the organocatalytic groups necessary
for this transformation, isolatation of the desired product
of the reactions was greatly simplified compared to when
Ph3P and PhOH are used. When a polymeric catalyst bear-
ing only phosphine groups (2) was examined, either low
or no yield of the desired product was obtained. Further-
more, we have extended the scope of this isomerization
reaction and for the first time report its application to
2(H)-pyran-2-one derivatives. It is anticipated that such
substrates can be used in the synthesis of natural products,
such as gymnoconjugatin B. Such synthetic studies and
the development of easily recyclable, heterogeneous ver-
sions of 1 are currently under way, and the results of these
studies will be reported in due course.
Next, we were inspired by the structure of gymnoconjuga-
tin B12 (Figure 1) and related natural products to see if
alkyne-substituted 2(H)-pyran-2-one derivatives could
also be isomerized by 1. For this study substrates 9a–c
(Figure 1) were synthesized according to known proce-
dures,13–15 and their isomerization was only studied using
catalyst 1.
O
O
O
OMe
gymnoconjugatin B
O
O
O
O
O
O
n-Bu
n-Bu
n-Bu
9a
9b
9c
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Figure 1 Gymnoconjugatin B and alkyne-substituted 2(H)-pyran-
2-one isomerization substrates
Acknowledgement
As can be seen in Table 3, when our standard isomeriza-
tion conditions using 1 were applied to 9a–c, high yield of
the desired product 10a–c was obtained in all cases. Thus,
the alkyne isomerization reaction might be useful in the
This research was supported financially by the University of Hong
Kong and the Research Grants Council of the Hong Kong S. A. R,
P. R. of China (Project No. HKU 704108P).
Synlett 2010, No. 17, 2617–2620 © Thieme Stuttgart · New York

2620
C. K.-W. Kwong et al.
LETTER
(9) Kwong, C. K.-W.; Huang, R.; Zhang, M.; Shi, M.; Toy,
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to its heterogeneous nature and poor swelling properties, it
was less efficient than a corresponding cross-linked
monofunctional analogue of 2. See ref. 8d for details.
(11) See Supporting Information for details.
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