A new ruthenium-catalyzed cyclopropanation of alkenes using propargylic acetates as a precursor of vinylcarbenoids

Article abstract of DOI:10.1016/S0040-4039(03)00219-3

[RuCl₂(CO)₃]₂ catalyzes intermolecular cyclopropanation of various alkenes with propargylic acetates to give vinylcycloropanes in good yields. The key intermediate of this reaction is a vinylcarbene complex generated by nucleophilic attack of the carbonyl oxygen of the acetate to an internal carbon of alkyne activated by the ruthenium complex.

Full text of DOI:10.1016/S0040-4039(03)00219-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2019–2022
A new ruthenium-catalyzed cyclopropanation of alkenes using
propargylic acetates as a precursor of vinylcarbenoids
Koji Miki, Kouichi Ohe* and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku,
Kyoto 606-8501, Japan
Received 27 December 2002; revised 21 January 2003; accepted 22 January 2003
Abstract—[RuCl2(CO)3]2 catalyzes intermolecular cyclopropanation of various alkenes with propargylic acetates to give vinyl-
cycloropanes in good yields. The key intermediate of this reaction is a vinylcarbene complex generated by nucleophilic attack of
the carbonyl oxygen of the acetate to an internal carbon of alkyne activated by the ruthenium complex. © 2003 Elsevier Science
Ltd. All rights reserved.
The in situ generation of carbenoid species from dia-
zoalkanes and transition metal complexes has been well
documented and the species are most applicable to
cyclopropanation and insertion reactions.1 Recently,
much attention has been paid to activation of alkynes
with transition metal complexes as another method to
generate carbenoid species. For example, cyclopropyl-
carbene–metal complexes in skeletal reorganization of
a,v-enynes,2,3 dialkylidene ruthenium species from v-
diynes,4 and tungsten-5 or gold6-containing carbonyl
ylides from o-ethynylphenylcarbonyl compounds are
considered as new entries to carbenoid species from
alkynes. Most recently, we have developed catalytic
cyclopropanation of alkenes through (2-furyl)carbene
complexes generated from ene–yne–carbonyl com-
pounds (Scheme 1a).7 A wide range of transition metal
compounds, such as Cr(CO)5(THF), [RhCl(cod)]2,
[RuCl2(CO)3]2, PdCl2, and PtCl2, was found to be effec-
tive as catalysts for the cyclopropanation. The key of
the reaction is 5-exo-dig cyclization via nucleophilic
attack of the carbonyl oxygen to an internal carbon of
alkyne leading to a stable furan structure as a reso-
nance form. This success stimulated us to develop a
new method to generate a vinylcarbenoid structure
from a simple propargylic carboxylate, in which nucleo-
philic attack of carbonyl oxygen followed by bond
cleavage at propargylic position in lieu of conjugated
system has been envisioned (Scheme 1b). Although this
concept was invalid in most cases due to facile isomer-
ization of propargylic acetates into allenyl acetates cat-
alyzed by transtion metal compounds,8 Rautenstrauch
first demonstrated the validity of protocol to provide a
vinylcarbenoid intermediate in palladium-catalyzed
reactions of propargylic acetate with dec-1-ene.9 Most
Scheme 1.
* Corresponding authors. Tel.: +81-75-753-5697; fax: +81-75-753-5697 (K.O.); Tel.: +81-75-753-5687; fax: +81-75-753-3573 (S.U.); e-mail: ohe
@scl.kyoto-u.ac.jp; uemura@scl.kyoto-u.ac.jp
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00219-3

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K. Miki et al. / Tetrahedron Letters 44 (2003) 2019–2022
recently, Fensterbank, Malacria, and Marco-Contelles
have demonstrated that intermediary vinylcarbenoids
are effectively trapped by an alkenyl moiety in the
molecule to give carbocycles in PtCl2-catalyzed cycliza-
tion of dienynes.10 To the best of our knowledge,
however, there have been no reports on efficient inter-
molecular reactions of alkenes and vinylcarbenoids gen-
erated from propargylic carboxylates. In this
communication, we wish to report a novel ruthenium-
catalyzed intermolecular [2+1] cycloaddition (cyclo-
propanation) between alkenes and propargylic acetates,
the latter of which can act as a vinylcarbenoid
precursor.
cyclopropanation, but it gave only allene 3 quantita-
tively (entry 3). [IrCl(cod)]2 and AuCl3 were also found
to catalyze the cyclopropanation to give 2a in 37% and
54% yields with 70:30 and 76:24 diastereomeric ratio,
along with 3 as a byproduct (entries 4 and 5). Particu-
larly, AuCl3 was highly active to both of cyclopropana-
tion and allene formation (entry 6). PtCl2, which can
act as a good catalyst for intramolecular cyclopropana-
tion (vide supra),10 catalyzed effectively the present
reaction, along with allene formation to some extent
(entry 7). GaCl3 was marginally effective in the cyclo-
propanation to give 2a in 26% yield with other uniden-
tified products (entry 8). Among catalysts examined,
Cr(CO)5(THF), [(p-cymene)RuCl2]2, PdCl2, and
9,12
PdCl2(CH3CN)2
were not effective for the present
First, we examined the cyclopropanation of styrene
with 2-methyl-3-butyn-2-yl acetate (1a) in the presence
of several catalysts which have been effective for (2-
furyl)carbene transfer cyclopropanation reaction.7
Results of catalyst-screening are given in Table 1.11 The
reaction of 1a and styrene in the presence of a catalytic
amount of [RuCl2(CO)3]2 (5 mol%) in toluene at 60°C
for 18 h afforded the cyclopropanated product 2a in
83% yield (cis:trans=84:16), along with 5% of allenyl
acetate 3 as a result of isomerization of 1a (entry 1).
The use of 10 mol% Ru catalyst completely suppressed
cyclopropanation.
Next, we examined cyclopropanation of styrene using
several propargylic acetates in the presence of
[RuCl2(CO)3]2 as a catalyst. These results are summa-
rized in Table 2. The reaction of propargylic benzoate
1b and styrene also gave the cyclopropanated product
2b in 81% yield (d.r.=88:12) (entry 1). Cyclic acetates
1c, 1d and 1e reacted with styrene to give the corre-
sponding products 2c, 2d, and 2e in 91, 69, and 60%
yields, respectively (entries 2–4). The reaction with sec-
ondary propargylic acetate 1f proceeded smoothly to
give 2f in 77% yield with a 75:25 diastereomeric ratio
(entry 5).13 Primary propargylic bezoate 1g was less
reactive in the present cyclopropanation and only a
trace amount of the expected products was obtained
after 48 h (entry 6). Next, the reactions of 1a with
several alkenes in the presence of [RuCl2(CO)3]2 were
examined (Table 3). The reaction of 1,1-
diphenylethylene with 1a proceeded smoothly to give
cyclopropane 2h in 66% yield (entry 1). 2-Ethylbut-1-
ene was slowly reacted with 1a to give 2i in 68% yield,
although the reaction required 20 equiv. of the alkene
(entry 2). On the other hand, cyclopropanation of
allyltrimethylsilane, tert-butyl vinyl ether, or vinyl ace-
tate with 1a resulted in giving lower yields of products,
43% (d.r.=67:33), 22% (cis:trans=36:64), and 20%
(cis:trans=75:25), respectively (entries 3–5). Oct-1-ene
or 3,3-dimethylbut-1-ene reacted with 1a to give the
corresponding products in lower yields (10–20%) with
several unidentified products. No cyclopropanation of
norbornene with 1a under the identical conditions was
observed. This result strongly supports that the present
cyclopropanation proceeds via different pathway from
cyclopropanation reported by Takahashi et al.14 In the
reaction of 20 equiv. of isoprene with 1a, more substi-
tuted double bond was selectively reacted to give trans-
2m in 40% yield together with 1,4-cycloheptadiene 4 in
31% yield (Scheme 2). The formation of 4 can be
explained by assuming [3,3]sigmatropic rearrangement
of initially produced cis-2m (Scheme 3).
the formation of
3
(entry 2). In contrast,
[Rh(OCOCF3)2]2 which is known as a good catalyst for
carbene transfer reaction could not catalyze the present
Table 1. Transition metal-catalyzed cyclopropanation of
styrene with 1aa
Entry [M]
Time
Yield (%)b
2a (cis:trans)c Allene 3
d
1
2
3
4
5
6e
7
8
[RuCl2(CO)3]2
[RuCl2(CO)3]2
18 h
15 h
30 min Trace
83 (84:16)
90 (86:14)
5
0
99
7
39
26
9
d
[Rh(OCOCF3)2]2
d
[IrCl(cod)]2
18 h
37 (70:30)
AuCl3
AuCl3
PtCl2
10 min 54 (76:24)
10 min 63 (79:21)
1 h
91 (68:32)
26 (65:35)
f
GaCl3
28 h
0
a Reactions of 1a (0.2 mmol) with styrene (1.0 mmol) in toluene (1.0
mL) were carried out in the presence of transition metal catalyst
(0.01 mmol) at 60°C under N2.
b GLC yield.
c Diastereomeric ratios were determined by 1H NMR or GLC.
d 0.005 mmol.
e 1 mol% of AuCl3 was used at room temperature.
f 1 M in methylcyclohexane.
In conclusion, we have developed an effective inter-
molecular cyclopropanation of various alkenes with
propargylic carboxylates via vinylcarbene complexes.
This also demonstrates versatility of alkynes as a car-
bene precursor in the transition metal-catalyzed reac-
tion. The present cyclopropanation is chemically

K. Miki et al. / Tetrahedron Letters 44 (2003) 2019–2022
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Table 2. Ru-catalyzed cyclopropanation of styrene with 1a
Table 3. Ru-catalyzed cyclopropanation of various alkenes
with 1aa
a
Reactions of 1a (0.2 mmol) with alkene (1.0 mmol) in toluene (1.0
mL) were carried out in the presence of [RuCl2(CO)3]2 (0.005 mmol)
at 60°C under N2.
b Isolated yield.
c Diastereomeric ratios were determined by 1H NMR or GLC.
d N.A.=not applicable.
a
Reactions of 1 (0.2 mmol) with styrene (1.0 mmol) in toluene (1.0
mL) were carried out in the presence of [RuCl2(CO)3]2 (0.005 mmol)
at 60°C under N2.
e Alkene (4.0 mmol) was used.
f Configuration is not yet known.
g 42 h.
b Isolated yield.
c Diastereomeric ratios were determined by 1H NMR or GLC, but
their configurations are not yet clear.
d Not determined.
equivalent to the reaction using a combination of a-di-
azoketone and transition metal compounds. This sys-
tem may find some applications in other catalytic vinyl-
carbene transfer reactions. These studies will be
reported in due course.
Acknowledgements
This work was supported by a Grant-in-Aid for Scien-
tific Research (B) (No. 14350468) from the Japan Soci-
ety for the Promotion of Science.
Scheme 2.

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K. Miki et al. / Tetrahedron Letters 44 (2003) 2019–2022
prepare allenyl acetates. See: (a) Schlossarczyk, H.;
Sieber, W.; Hesse, M.; Hansen, H.-J.; Schmid, H. Helv.
Chim. Acta 1973, 56, 875; (b) Oelberg, D. G.; Schiavelli,
M. D. J. Org. Chem. 1977, 42, 1804; (c) Cookson, R. C.;
Cramp, M. C.; Parsons, P. J. J. Chem. Soc., Chem.
Commun. 1980, 197 and references cited therein.
9. (a) Rautenstrauch, V. Tetrahedron Lett. 1984, 25, 3845;
(b) Rautenstrauch, V. J. Org. Chem. 1984, 49, 950; (c)
The oxidative rearrangement of propargyl esters by palla-
dium catalyst has been reported. See: Kataoka, H.;
Watanabe, K.; Goto, K. Tetrahedron Lett. 1990, 31,
4181.
Scheme 3.
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cis-2a: A colorless oil; IR (neat) 701, 733, 776, 1113,
1
1155, 1183, 1218, 1369, 1751 (CꢀO), 2916 cm−1; H NMR
(CDCl3, 270 MHz, 25°C): l 1.02 (ddd, J=5.4, 6.3, 6.3
Hz, 1H), 1.25 (ddd, J=5.4, 8.9, 8.9 Hz, 1H), 1.41 (s, 3H),
1.47 (s, 3H), 2.04 (s, 3H), 2.20–2.33 (m, 2H), 7.01–7.26
(m, 5H); 13C NMR (CDCl3, 67 MHz, 25°C): l 11.6, 17.5,
18.6, 20.6, 21.7, 24.2, 123.2, 125.4, 127.2, 127.4, 138.1,
139.1, 169.1. Anal. calcd for C15H18O2: C, 78.23; H, 7.88.
Found: C, 78.49; H, 7.85%.
trans-2a: A colorless oil; IR (neat) 698, 760, 1102, 1159,
1196, 1214, 1369, 1749 (CꢀO), 2917 cm−1 1H NMR
;
(CDCl3, 270 MHz, 25°C): l 1.02 (dd, J=7.3, 7.3 Hz,
2H), 1.57 (s, 3H), 1.79 (s, 3H), 1.94–2.09 (m, 2H), 2.16 (s,
3H), 7.06–7.30 (m, 5H); 13C NMR (CDCl3, 67 MHz,
25°C): l 14.7, 18.2, 18.8, 20.6, 23.2, 23.5, 120.5, 125.7,
125.8, 128.3, 140.6, 141.9, 169.1. Anal. calcd for
C15H18O2: C, 78.23; H, 7.88. Found: C, 77.96; H, 7.91%.
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