An improved 1,3-diene synthesis from alkyne and ethylene using cross-enyne metathesis

Article abstract of DOI:10.1016/S0040-4039(02)00215-0

Synthesis of 1,3-diene from alkyne and ethylene (1 atm) was improved using ruthenium carbene complex 1b having heterocyclic carbene as a ligand. In this reaction, the heteroatom at the propargylic position was not required, although the reaction of alkyne

Full text of DOI:10.1016/S0040-4039(02)00215-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2235–2238
An improved 1,3-diene synthesis from alkyne and ethylene
using cross-enyne metathesis
Keisuke Tonogaki and Miwako Mori*
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Received 28 December 2001; revised 21 January 2002; accepted 25 January 2002
Abstract—Synthesis of 1,3-diene from alkyne and ethylene (1 atm) was improved using ruthenium carbene complex 1b having
heterocyclic carbene as a ligand. In this reaction, the heteroatom at the propargylic position was not required, although the
reaction of alkyne with the first-generation ruthenium carbene complex 1a was affected by the substituent at the propargylic
position. Various 1,3-dienes could be synthesized from alkynes and ethylene. © 2002 Published by Elsevier Science Ltd.
1
,2
Although cross-enyne metathesis is very interesting, it
is difficult to use cross-enyne metathesis in synthetic
3
organic chemistry because olefin metathesis, enyne
metathesis and diyne metathesis would occur simulta-
neously. During the course of our study on enyne
4
metathesis, we developed a novel method for synthe-
sizing 1,3-diene 3 from alkyne 2 and ethylene using
2
cross-enyne metathesis. The reaction procedure is very
Scheme 1. Novel synthesis of 1,3-diene from alkyne and
ethylene.
simple: a CH Cl solution of alkyne 2 and 3–10 mol%
2
2
5
of ruthenium carbene complex 1a reported by Grubbs
was stirred under ethylene gas (1 atm) for 1–2 days at
room temperature to give 1,3-diene 3 in good to moder-
ate yield (Scheme 1). This reaction was further extended
6a
using high pressure of ethylene gas.
In this reaction, if alkynes 2 have an acetoxy, benzoyl-
oxy or tosylamide group at the propargylic position,
1
,3-dienes 3 were obtained in good yields. However,
alkynes 2 that did not have these groups at the propar-
gylic position afforded 1,3-dienes 3 in poor yields.
2b
Figure 1.
The effect of the heteroatom at the propargylic position
is thought to arise because the carbonyl group of the
acyl moiety coordinates with the ruthenium metal and
2c,7
then the reaction proceeds as shown in Fig. 1.
Dur-
cross-enyne metathesis of alkyne and allylsilane using
3d
ing the synthetic study of anolignan A and anolignan
1b, and Diver has investigated cross-enyne metathesis
2
c
B, we used the second-generation ruthenium carbene
of terminal alkynes having a heteroatom at the propar-
8
6b,c
complex 1b, which has heterocyclic carbene as a lig-
gylic position under 60 psi of ethylene using 1b.
and, and high reactivity of 1b was observed in the
synthesis of 1,3-dienes from alkynes. Thus, we decided
to reinvestigate the synthesis of 1,3-dienes from alkynes
and ethylene. Blechert has recently reported improved
At first, the effect of the acetoxy group at the propar-
gylic position was examined. When a CH Cl solution
of alkyne 2a with 5 mol% of first-generation Grubbs’
catalyst 1a was stirred under 1 atm pressure of ethylene
2
2
(
balloon) at room temperature for 48 h, the desired
*
0
Corresponding author.
1,3-diene 3a was obtained in 16% yield (Table 1, run 1).
040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)00215-0

2
236
Table 1. Effects of heteroatom at the propargylic position
Reaction conditions
K. Tonogaki, M. Mori / Tetrahedron Letters 43 (2002) 2235–2238
Yield (%)
Run
R1
Ru
(mol %)
Solvent
CH Cl
Temp. (°C)
Time (h)
3
2
1
2
3
4
5
6
7
2a
2a
2b
2a
2a
2b
2b
H
H
OAc
H
H
1a
1a
1a
1b
1b
1b
1b
5
5
5
10
5
10
5
rt
Reflux
rt
80
80
48
24
48
5
0.5
0.5
0.5
16
—
75
91
83
69
84
23
—
—
—
—
2
2
2
2
CH Cl
2
CH Cl
2
Toluene
Toluene
Toluene
Toluene
OAc
OAc
80
80
100
100
Ph
R1
in 33 and 46% yields, respectively (run 2). These results
indicate that the reaction of 2a with 1b is slightly faster
than that of 2b with 1b. It means that in the cross enyne
metathesis with ethylene using 1b, the electronic effect
of the acetoxy group at the propargylic position is not
important (Scheme 3).
R1
Ru
1
MeO
H C CH2
MeO
2
2
3
(
1 atm)
Scheme 2. Synthesis of 1,3-diene from terminal alkyne and
ethylene.
Various alkynes 2 were treated with 1a and 1b under
ethylene gas (1 atm), and the results are shown in Table
3
. The reaction of terminal alkynes 2c bearing a phenyl
group or 2d bearing an alkyl group proceeded smoothly
to give 1,3-dienes 3c and 3d in high yields, respectively,
after only 30 min. Internal alkynes 2e, 2f and 2g also
gave 1,3-dienes, 3e, 3f and 3g in high yields. The effect
of TMS group on alkyne was examined because in
intramolecular enyne metathesis using 1a, enyne having
When the reaction was carried out in a similar manner
upon heating, none of the product was obtained
because 1a was not stable under these reaction condi-
9
tions (run 2). However, alkyne 2b having an acetoxy
group at the propargylic position was treated with 1a in
a similar manner at room temperature to give desired
4
a
the TMS group on alkyne did not give a good result.
1,3-diene 3b in 75% yield (run 3). It is clear that in the
The reaction of 2h bearing TMS group on alkyne with
ethylene using 1a gave 1,3-diene 3h in 21% yield after
reaction of alkyne and ethylene with 1a, the acetoxy
group at the propargylic position is very important. On
the other hand, when compound 2a having no acetoxy
group at the propargylic position was treated with 10
mol% of second-generation ruthenium carbene complex
1
6 h, while that using 1b gave 3h in 87% yield. The
resulting 1,3-diene 3h has a vinyl silane moiety, which
would be a useful precursor in synthetic organic
chemistry.
1
b upon heating in toluene, the desired 1,3-diene 3a was
obtained in 91% yield after 5 h (run 4) (Scheme 2).
The reaction of alkyne 2i having a carbomethoxy group
with 1a did not proceed at room temperature or upon
Using 5 mol% of 1b in toluene, 3a was obtained in 83%
yield after only 30 min (run 5). In a similar manner, 2b
gave 3b in quantitative yield after 30 min (runs 6 and
OAc
1b
7). These results indicate that even in the absence of an
H2C CH2 (1 atm)
+
acetoxy group at the propargylic position, ruthenium
carbene complex 1b is quite effective for the synthesis
of 1,3-diene.
MeO
toluene, 30 min
MeO
2a
2b
OAc
To confirm whether an acetoxy group at the propar-
gylic position is effective for the synthesis of 1,3-diene,
a competitive reaction was carried out. A toluene solu-
tion of a mixture of equal molar amounts of 2a and 2b
and 2.5 mol% of 1b was stirred upon heating at 80°C
for 30 min. After the addition of ethyl vinyl ether and
then the usual work-up, the crude product was purified
by short column chromatography on silica gel to
+
MeO
MeO
3a
3b
Scheme 3. Competitive reaction of 2a and 2b using 1b.
1
Table 2. Competitive reaction of 2a and 2b with 1b
remove the catalyst. The H NMR spectrum of the
reaction mixture showed that 1,3-dienes 3a and 3b were
formed in 77 and 66% yields, respectively, along with
the recovered starting materials 2a and 2b in 17 and
Yield (%)
Run
Ru (mol %)
Temp. (°C)
3a
3b
2a
2b
34% yields, respectively (Table 2, run 1). The reaction
was carried out at 50°C using 1 mol% of 1b. After 30
min, 3a and 3b were obtained in 53 and 48% yields,
respectively, along with the starting materials 2a and 2b
1
2
2.5
1
80
50
77
53
66
48
17
33
34
46

K. Tonogaki, M. Mori / Tetrahedron Letters 43 (2002) 2235–2238
Table 3. Synthesis of various 1,3-dienes
2237
yield (%)
temp.
time
(h)
alkyne
diene
"Ru" mol % (°C)
2
3
80a)
—
1
2
3
4
5
6
7
1b
5
0.5
0.5
88
MeO
MeO
3
c
2
c
d
80a)
—
1b
5
71
3
d
e
2
CH3
80a)
—
—
1b
5
5
0.5
0.5
85
2e
3
OAc
80a)
1b
100
OAc
2f
3f
refluxb)
1
b
a
5
24
80
—
2g
3g
TMS
rtb)
80a)
1
5
5
16
16
21
87
78
10
TMS
MeO
1b
MeO
3h
2h
COOMe
reflux b) 16
—
—
33
43
1a
1a
1b
1b
10
10
5
93
70
67
34
rtb)
16
16
16
COOMe
MeO
80a)
MeO
80a)
10
2i
3i
a) in toluene. b) in CH2Cl2.
heating, and the starting material 2i was recovered
unchanged after 16 h (run 7). Although the reaction
rate of 2i with ethylene using 1b was slow, the desired
These results indicate that 1,3-diene synthesis from
alkyne and ethylene (1 atm) was improved. The
remarkable feature of the reaction using 1b is as fol-
lows. The reaction procedure is very simple; that is, a
solution of alkyne and 1b (1–5 mol%) in toluene or
CH Cl is stirred at 50–80°C under ethylene gas, and 1
1
,3-diene 3i was obtained in 43% yield along with 2i in
34% yield after 16 h.
2
2
In the internal alkyne, competitive reaction between
alkyne 2e having no substituent at the propargylic
position and alkyne 2f having an acetoxy group at the
same position was carried out. Since the reactions of
these compounds with ethylene using 1b were very fast,
the reaction was carried at 50°C in toluene using 1
mol% of ruthenium catalyst. However, after only 15
min, the spots of the starting materials 2e and 2f were
completely disappeared on TLC and both 3e and 3f
were obtained in almost quantitative yields, respec-
tively. It was confirmed that an acetoxy group at the
propargylic position in the internal alkyne did not also
affect the reaction rate in the cross-enyne metathesis
atm pressure of ethylene can be used. In this reaction,
CH3
1 mol % 1b
OAc
H2C CH2
+
toluene, 50 °C
2e
2f
+
CH3
(93%)
OAc
3e
3f (100%)
(
Scheme 4).
Scheme 4. Competitive reaction of internal alkynes 2e and 2f.

2
238
K. Tonogaki, M. Mori / Tetrahedron Letters 43 (2002) 2235–2238
functional groups such as a phenyl group, alkyl group,
TMS group and even a carbomethoxy group on alkyne
were tolerated and various 1,3-dienes were obtained in
good to high yields. The presence or absence of an
acetoxy group at the propargylic position did not affect
the reaction rate to form 1,3-diene. Further studies are
in progress.
1995, 34, 1833; (d) F u¨ rstner, A. Topics in Organometallic
Chemistry; Springer-Verlag: Berlin, Heidelberg, 1998; Vol.
1; (e) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413; (f) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1
1998, 371; (g) Phillips, A. J.; Abell, A. D. Aldrichimica
Acta 1999, 32, 75; (h) F u¨ rstner, A. Angew. Chem., Int. Ed.
2000, 39, 3013. Enyne metathesis: (i) Mori, M. In Top.
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Heidelberg, 1998, Vol. 1, p. 133; (j) Trnka, T. M.; Grubbs,
R. H. Acc. Chem. Res. 2001, 34, 18.
General procedure for synthesis of 1,3-diene from alkyne
using 1b. A solution of alkyne 2 and 1–5 mol% of 1b
was heated in CH Cl or toluene at 50–80°C under
2
2
4. (a) Kinoshita, A.; Mori, M. Synlett 1994, 1020; (b)
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Mori, M.; Sakakibara, N.; Kinoshita, A. J. Org. Chem.
ethylene gas (1 atm). After the spot of the starting
material disappeared on TLC, ethyl vinyl ether (several
drops) was added. The solvent was removed and the
residue was purified by short column chromatography
on silica gel to give 1,3-diene 3.
1998, 63, 6082; (e) Mori, M.; Kitamura, T.; Sakakibara,
N.; Sato, Y. Org. Lett. 2000, 2, 543; (f) Mori, M.; Kita-
mura, T.; Sato, Y. Synthesis 2001, 654; (g) Kitamura, T.;
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mura, T.; Sato, Y. Chem. Commun. 2001, 1258.
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