Ring size-selective ring-closing olefin metathesis: Taking advantage of the deleterious effect of ethylene gas

Article abstract of DOI:10.1002/adsc.201000944

The deleterious effect of ethylene gas on the ring-closing olefin metathesis (RCM) for the formation of 5- to 8-membered rings was investigated. Significant rate differences caused by ethylene gas were observed among the different ring-size formation reac

Full text of DOI:10.1002/adsc.201000944

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DOI: 10.1002/adsc.201000944
Ring Size-Selective Ring-Closing Olefin Metathesis: Taking
Advantage of the Deleterious Effect of Ethylene Gas
Kazuhiro Yoshida,a,* Yuto Kano,a Hidetoshi Takahashi,a and Akira Yanagisawaa,*
a
Department of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Fax : (+81)-43-290-2789; e-mail: kyoshida@faculty.chiba-u.jpayanagi@faculty.chiba-u.jp
Received: December 14, 2010; Published online: May 17, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000944.
Abstract: The deleterious effect of ethylene gas on
the ring-closing olefin metathesis (RCM) for the
formation of 5- to 8-membered rings was investigat-
ed. Significant rate differences caused by ethylene
gas were observed among the different ring-size for-
mation reactions. Nevertheless, the rate differences
can be advantageously utilized for chemoselective
RCM.
On these grounds, we have come to the conclusion
that the generality of this type of selectivity is worthy
of study. Here we report the results of our investiga-
tion in which rate differences caused by ethylene gas
among 5- to 8-membered ring formation reactions
were observed and the deleterious effect of ethylene
gas could be used to improve selectivity in RCM syn-
thesis of favorable ring sizes by limiting the formation
of less-favorable ring sizes.
Keywords: homogeneous catalysis; metathesis; ring
closure; ring size-selective reaction; ruthenium
The easily prepared nitrogen-containing dienes 7a–
d[10] were adopted as model substrates for this investi-
gation (Scheme 2). While holding the pressure con-
stant at 1 atm, we first compared the yields of RCM
products 8a–d under nitrogen gas with those under
ethylene gas in the range of 0 to 808C using 1 mol%
The utilization of ring-closing olefin metathesis
(RCM) has seen an explosive growth in organic
chemistry over the past two decades.[1] This outstand-
ing reaction, however, is still hampered by some diffi-
cult problems. The chemoselective RCM of substrates
with more than two multiple bonds available for the
metathesis is one of the problems.[2,3]
During the course of our study, which is aimed at
the development of new methods for the synthesis of
aromatic compounds,[4] we recently tried to synthesize
fused bicyclic benzenes 4 and 5 by applying the ring-
closing enyne metathesis (RCEM)/RCM sequence to
a mixture of trienyne 1 and its isomer 2[5] (1:2=10:1)
using Grubbsꢀ second-generation catalyst 3[6]
(Scheme 1). As expected, under nitrogen gas, the re-
action proceeded to produce 4 and 5 with double ring
closing. However, under ethylene gas,[4c,7] the products
1
detectable by H NMR were only 4 and 6. Our sur-
prise came not from the formation of 6 that should be
formed from 2 by RCEM only, but from the absence
of the corresponding RCEM product from 1, indicat-
ing that ring-size selectivity was observed between the
six- and seven-membered ring formation reactions
under ethylene gas.[8,9]
Scheme 1. Incidentally observed ring size-selective RCM in
which ethylene gas hindered only the RCM for 7-membered
ring formation.
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Scheme 2. Investigation of deleterious effect of ethylene gas on RCM of 7a–d.[a]
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Ring Size-Selective Ring-Closing Olefin Metathesis
Table 1. Ring size-selective RCM between 5- and 6-membered rings.[a]
Entry
Atmosphere
T [8C]
Yield of 10 [%][b]
Yield of 11 [%][b]
[d]
1[c]
2
3
4
5
N2 (1 atm)
N2 (1 atm)
N2 (1 atm)
C2H4 (1 atm)
C2H4 (3 atm)
C2H4 (3 atm)
0
>95
81
–
20
60
20
20
60
19
<35[e]
55
<15[e]
44
30[f]
7
67[f]
93
6
[a]
The reaction was carried out with 9 and ruthenium catalyst (3, 5 mol%) in toluene (0.01M) for 2 h under a nitrogen or
ethylene atmosphere. The reaction was quenched by the addition of di(ethylene glycol)vinyl ether.
The yield was determined by H NMR analysis of the crude mixture using 1,4-bis(trimethylsilyl)benzene as the internal
[b]
1
standard.
The reaction was carried out for 7 h.
The product was not detected by H NMR analysis.
[c]
[d]
[e]
1
The yield could not be determined precisely due to the formation of significant amount of oligomer products whose
1H NMR signals overlap those of 10 and 11, and the oligomers could not be separated from 10 and 11 by silica gel chro-
matography.
3% of 9 was recovered.
[f]
of catalyst 3 (Graphs 1–4 in Scheme 2). As predicted, uct. When the reaction was carried out at 08C under
ethylene hindered the progress of the reaction for all nitrogen gas, only 10 was formed as a product detect-
1
the substrates.[11,12] However, the degree of the hin- able by H NMR (entry 1). Increasing the tempera-
drance varied with each ring formation and seemed to ture to 208C gave 10 in 81% yield and 11 in 19%
have the following order: 8-membered ring@7-mem- yield, indicating that 10 and 11 are kinetically favored
bered ring>5-membered ring@6-membered ring.[13,14] and thermodynamically favored products, respectively
We were particularly interested in the contrast be- (entry 2). Although a further increase in temperature
tween the nearly complete hindrance of the 8-mem- to 608C favored the formation of 11 to that of 10,
bered ring formation and the only slight hindrance of side reactions that yielded non-negligible amounts of
the 6-membered ring formation by ethylene.
by-products, most of which were assigned to oligo-
While holding the temperature constant for each mers arising from the cross metathesis, complicated
ring-size formation, the effect of ethylene pressure the crude reaction mixture (entry 3). On the other
(1–3 atm)[15] was examined next (Graphs 5–8 in hand, when the reaction was carried out at 208C
Scheme 2). As predicted, the deleterious effect of eth- under 1 atm of ethylene gas, cyclohexene 11 was
ylene increased gradually as the pressure increased, formed as the major product (entry 2 vs. 4). The reac-
and the trend of the relationship between the ring tion conducted under 3 atm of ethylene gas promoted
size and the degree of the hindrance by ethylene was the formation of 11 further (entry 5), and it was
similar to that observed in Graphs 1–4 (Scheme 2). found that the reaction at 608C under 3 atm of ethyl-
Thus, the degree of the hindrance seemed to have the ene gas furnished 11 as the predominant product
following order: 8-membered ring@7-membered (entry 6).[16] Under the conditions using ethylene gas,
ring>5-membered ring@6-membered ring. The ro- side reactions to give oligomers were not observed.
bustness of the 6-membered ring formation to the This result implies that ethylene hindered the prog-
hindrance by even a pressure of 3 atm of ethylene to ress not only of the 5-membered ring formation reac-
give 8b is noteworthy, whereas the formation reac- tion, but also of oligomerization (entry 3 vs. 6).[17]
tions of other ring sizes were completely inhibited by
2–3 atm of ethylene.
Finally, we attempted the selective synthesis of 5
and 6 using 2 as the sole substrate (Table 2). Under
We next investigated the RCM of triene 9 for the nitrogen gas for 2 h, RCEM/RCM product 5 was
direct observation of ring size selectivity (Table 1). formed as the major product, but it was found that
The RCM of 9 is expected to produce two cyclic com- RCEM product 6 was also formed as the minor prod-
pounds, cyclopentene 10 as a 5-membered ring prod- uct (entry 1). Prolonging the reaction time to 4 h com-
uct, and cyclohexene 11 as a 6-membered ring prod- pleted the formation of 5, and 6 was not detected at
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Kazuhiro Yoshida et al.
Table 2. Application of the ethylene effect to the selective synthesis of fused bicyclic benzene 5 and single-ring benzene 6.[a]
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Entry
Atmosphere
t [h]
Yield of 5 [%][b]
Yield of 6 [%][b]
1
2
3
4
N2 (1 atm)
N2 (1 atm)
C2H4 (1 atm)
C2H4 (2 atm)
2
4
2
2
79
>95
11
21
–
89
>95
[c]
[c]
–
[a]
The reaction was carried out with 2 and ruthenium catalyst (3, 7.5 mol%) in toluene (0.01M) under a nitrogen or ethyl-
ene atmosphere at 808C. The reaction mixture was treated with p-toluenesulfonic acid (10 mol%) at room temperature
for 1 h.
[b]
[c]
1
The yield was determined by H NMR analysis of the crude mixture using 1,4-bis(trimethylsilyl)benzene as the internal
standard.
1
The product was not detected by H NMR analysis.
1
all by H NMR (entry 2). Under 1 atm of ethylene
gas, the proportion of 5 and 6 was changed dramati-
cally, and the formation of 6 was predominant
(entry 3). Increasing ethylene pressure to 2 atm was
sufficient to obstruct the 7-membered ring formation
completely to give 6 as the only detectable product
(entry 4).
reaction mixture was stirred for 2–7 h at the same tempera-
ture. The reaction was quenched by adding di(ethylene gly-
col)vinyl ether (53.9 mg, 0.408 mmol, 400 mol%) and the
yield was determined by H NMR analysis of crude mixture
using 1,4-bis(trimethylsilyl)benzene as the internal standard.
1
General Procedure for the Synthesis of Cyclic Com-
pounds 8, 10, 11, 5, and 6 [under Ethy-lene Atmos-
phere (2–3 atm)]
When equilibrium is considered, the strategy of per-
forming RCM under ethylene gas seems to be an un-
conventional one. However, in the case in which com-
petitive side reactions (e.g., another RCM or oligome-
rization) exist, performing the reaction under ethyl-
ene gas offers great benefits to control the chemose-
lectivity due to the rate differences caused by
ethylene. Needless to say, selectivity can be effectively
controlled by changing the reaction temperature, cat-
alyst structure, solvent, and so on. It seems, however,
that the effect of ethylene or inhibitors of equal abili-
ty is also of value for controlling selectivity. Our on-
going study is focused on the examination of the
effect with other catalysts, the effect on substrates
having other substituent patterns, and the mechanistic
interpretations of the selectivity.
The reaction was conducted in a Fischer–Porter vessel. To a
solution of 7, 9, or 2 (0.102 mmol) in toluene (10.2 mL) was
added a solution of catalyst 3 (1–7.5 mol%, 0.01M, 1.02–
7.65 mmol) under nitrogen at 08C. Then, the system was
evacuated carefully and filled with ethylene gas (2–3 atm) in
three cycles. The reaction vessel was placed in a bath main-
tained at 0–808C and the pressure was immediately read-
justed to 2 or 3 atm by leaking excess gas. The reaction mix-
ture was stirred for 2 h and quenched by adding di(ethylene
glycol)vinyl ether (53.9 mg, 0.408 mmol, 400 mol%). The
1
yield was determined by H NMR analysis of crude mixture
using 1,4-bis(trimethylsilyl)benzene as the internal standard.
Acknowledgements
We appreciate the financial support from a Grant-in-Aid for
Young Scientists (WAKATE B-20750069) from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan.
Experimental Section
General Procedure for the Synthesis of Cyclic Com-
pounds 8, 10, 11, 5, and 6 [under Nitrogen or Ethy-
lene Atmosphere (1 atm)]
To a solution of 7, 9, or 2 (0.102 mmol) in toluene (10.2 mL)
was added a solution of catalyst 3 (1–7.5 mol%, 0.01M,
1.02–7.65 mmol) under nitrogen or ethylene at 0–808C. The
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Ring Size-Selective Ring-Closing Olefin Metathesis
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